Understanding Testosterone and Muscle Preservation | Shalin Shah

Summary

Podcast Summary: Understanding Testosterone and Muscle Preservation | Shalin Shah

Episode Title: Understanding Testosterone and Muscle Preservation
Host: Dr. Gabrielle Lyon
Guest: Shalin Shah, CEO of Marius Pharmaceuticals
Release Date: November 15, 2024

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Introduction

In this enlightening episode of The Dr. Gabrielle Lyon Show, Dr. Gabrielle Lyon welcomes Shalin Shah, the CEO of Marius Pharmaceuticals. The conversation delves deep into the realm of testosterone therapy, focusing on the groundbreaking oral testosterone drug, Kaisertrex, which has recently received FDA approval.

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Background of Shalin Shah and Marius Pharmaceuticals

Shalin Shah brings a unique perspective to the table, combining his extensive investment background with a passion for addressing underappreciated health assets. Under his leadership, Marius Pharmaceuticals has been pivotal in developing and bringing Kaisertrex to market. Dr. Lyon shares a personal connection, mentioning her husband’s collaboration with Dr. Mohakira at Baylor, highlighting the strong network supporting their endeavors.

Notable Quote:

Shalin Shah at [00:57]: "Testosterone has been around for almost 100 years, and you just have these periods where I think the public and the medical community have been scared."

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The History and Evolution of Oral Testosterone

The discussion traces the origins of oral testosterone back to its isolation in 1935. Despite its early inception, oral testosterone faced significant hurdles due to liver toxicity, leading to a preference for injectable forms. It wasn't until the 1970s that a non-liver-toxic oral testosterone formulation emerged, albeit with its own challenges like frequent dosing and dietary restrictions.

Notable Quote:

Shalin Shah at [05:22]: "The first oral testosterone was when they actually isolated testosterone in 1935. So it was almost 100 years... but it was liver toxic."

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Current Challenges with Testosterone Therapy

Shalin Shah highlights the persistent misconceptions surrounding testosterone therapy. Approximately 50% of the population is unaware of testosterone's importance, while another 40% holds unfavorable beliefs about its risks, such as cardiovascular issues and prostate cancer. This skepticism extends even to some medical professionals who may not stay updated with the latest research.

Notable Quote:

Shalin Shah at [08:35]: "Testosterone has been a very misunderstood molecule, to be honest."

Furthermore, the scheduling of testosterone as a controlled substance in the 1990s has created significant barriers, making access difficult and altering public perception negatively.

Notable Quote:

Shalin Shah at [12:07]: "We are launching a nonprofit that descheduling is a core tenant of our mission."

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Kaisertrex: A Breakthrough in Testosterone Therapy

Kaisertrex stands out as an innovative oral testosterone solution that addresses many of the shortcomings of previous formulations. Unlike injectables, Kaisertrex is absorbed lymphatically through the small intestine, reducing liver toxicity and the need for multiple daily doses. This advancement offers greater convenience and adherence for patients.

Notable Quote:

Shalin Shah at [28:22]: "The half-life is around five, six hours. You take a dose in the AM and a dose in the PM."

Kaisertrex maintains testosterone levels within a physiological range, avoiding the spiked levels commonly associated with injections. This steady approach minimizes risks like elevated hematocrit and blood pressure.

Notable Quote:

Shalin Shah at [30:39]: "For Kaisertrex, sub 2% of our patients developed a hematocrit level above 54."

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Impact on Metabolic Health and Fertility

The conversation emphasizes testosterone's role in metabolic health, including its influence on conditions like prediabetes, type 2 diabetes, osteoporosis, and depression. Kaisertrex's design supports maintaining hormonal balance without significantly disrupting natural processes, thereby preserving fertility and reducing risks like testicular atrophy.

Notable Quote:

Shalin Shah at [34:23]: "We're not seeing reports of testicular atrophy, which is a huge concern with other forms of testosterone therapy."

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The Testosterone Project: Advocating for Change

Shalin Shah introduces the "Testosterone Project," a nonprofit initiative aimed at revolutionizing testosterone therapy. The project focuses on:

1. Standardizing Testosterone Testing: Advocating for routine testosterone screenings for both men and women over 40.
2. Promoting Female Testosterone Research: Addressing the lack of FDA-approved testosterone treatments for women by supporting targeted research.
3. Descheduling Testosterone: Working towards removing testosterone from its controlled substance status to enhance accessibility.

Notable Quote:

Shalin Shah at [46:05]: "Testosterone is a female hormone as well, and we need to recognize its importance beyond sexual dysfunction."

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Future Directions and Expanding Applications

Looking ahead, Shalin Shah envisions Kaisertrex becoming a staple in testosterone therapy, not just for treating hypogonadism but also as a preventive measure against metabolic diseases. The potential for synergistic applications with other therapies, such as GLP-1 agonists, is also explored, hinting at comprehensive approaches to combating conditions like diabetes and muscle loss.

Notable Quote:

Shalin Shah at [77:43]: "In five years, if we are successful with that science and education, you could see 10 million men in the US on Kaisertrex and more globally."

Additionally, the global interest in testosterone therapy, especially in regions with high diabetes prevalence like Saudi Arabia and the UAE, underscores its universal relevance and potential impact.

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Conclusion

Shalin Shah's insights shed light on the transformative potential of Kaisertrex in the testosterone therapy landscape. By addressing historical challenges, enhancing accessibility, and advocating for scientific advancement, Marius Pharmaceuticals is poised to make significant strides in improving metabolic health and overall well-being.

Final Notable Quote:

Shalin Shah at [79:28]: "We're committed to the research and education needed to change the way this therapy is viewed and utilized."

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Note: This summary is based on the provided transcript and is intended for informational purposes only. It does not constitute medical advice. Always consult a healthcare professional for medical concerns.

Transcript

[Dr. Gabrielle Lyon]

Welcome to the Dr. Gabrielle Lyon show, where cutting edge science meets innovation and practical application for everybody. In today's episode, I sit down with the Metabolic CEO Shalin Shah. He's the CEO for Marius Pharmaceuticals, and he's brought the FDA approved drug Kaisertrex, which is oral testosterone, to market. In this episode, we sit down and we learn all about testosterone, where testosterone has come from, where it is in the present space, in the pharmaceutical industry, and so much more. Please join me in sitting down with Shailen Shah. This episode has been supported by Marius Pharmaceuticals. Shalin Shah, welcome to the podcast.

[Shalin Shah]

Thank you for having me.

[Dr. Gabrielle Lyon]

I am. I'm actually really, really excited to have this conversation. I want to give you a little bit of a backstory, which I don't know if you know this. So you are the CEO of Marius Pharmaceuticals and which, by the way, has been instrumental in the development and FDA approval of something called Kaisertrex, which is oral testosterone.

[Shalin Shah]

Yep.

[Dr. Gabrielle Lyon]

Okay, so let's talk about. Let's just give the listeners a little bit of a background. My husb is. So he was a former Navy SEAL who is now in his second year of urology residency, happens to be at Baylor, which is one of the number one places that one would be able to study andrology, specifically testosterone and other anabolics. Who works underneath Dr. Mohakira, who, by the way, is a very good friend of yours and who's also doing some of the really pivotal research.

[Shalin Shah]

Yep. Mo is a close advisor and friend and has really been helpful in bringing light to obviously, the therapy and kaisertrex.

[Dr. Gabrielle Lyon]

Itself, which is amazing. So I said, you know, from me, from my perspective as someone who sees patients, I was always thinking that really the most effective route and understanding of testosterone would be injectable. And there were various challenges that I was having with some of my patients. Like, for example, when you inject testosterone, you might see a quick elevation in hematocrit. Right. And for the listener, for the other physicians knowing, you know, listening, there might be a risk of. I mean, whether it is a perceived risk or relative risk, it is still within the guidelines that you would need to really monitor hematocrit and treat it specifically. Which brings me to when I called him, I said, okay, Mo, what are my options? And I had never heard about KaiserRex before or any form of oral, which I assume. And from what I understand, there are three. Oral testosterone. Yep. So that was a very long winded way of welcoming you to the podcast. And I'm so excited to learn you've really Been doing some very instrumental work.

[Shalin Shah]

No, I appreciate that. And again, super glad to be here. I think there's a lot that the general population needs to know. Testosterone has a very. It's a very misunderstood molecule, to be honest. Right. And I think it's very important for patients and prospective patients to understand what it does, what its role is, and then, yes. What the options are, what's going to fit them. But we are really excited about Kaisertrex because I think not only oral has solved an administration problem, pain, quite literally a pain that's been out there. But the efficacy and safety data that we continue to unfold I think make it more and more compelling that this will be the standard of care.

[Dr. Gabrielle Lyon]

Can you tell me a little bit about. Well, you know, I'm curious as to how you got involved in this, because I do think that there is something really important in the conversation of being able to separate, quote, Big Pharma and pharmaceutical interventions like testosterone therapy.

[Shalin Shah]

Sure. So I have an investment background. I've been doing that all my career.

[Dr. Gabrielle Lyon]

And you did your undergrad at Rutgers, by the way.

[Shalin Shah]

Yep. I was in.

[Dr. Gabrielle Lyon]

Small world.

[Shalin Shah]

Exactly. So also a Northeast, I guess, resident in that sense. But yeah. So I've had this background and we've generally looked at, let's call it underappreciated assets and finding value within them. So Kaisertrax was in development since 2009, and this all happened in the RTP area, and that's where Marius is headquartered. So, great data. The formulation that it developed was very unique. It actually used something called phytosterols, which plant sterols are often used as supplement products for heart health and so forth. So that's really how they crack the code on oral, because oral, again, was notoriously hard to develop. Going back to very early days, it was always liver toxic. So they had to find a way that it was lymphatically absorbed, which, again, that's through the small intestine.

[Dr. Gabrielle Lyon]

And when was the first. The first oral testosterone was how long ago?

[Shalin Shah]

So actually, interestingly enough, the first oral testosterone is when they actually isolated testosterone in 1935. So it was almost 100 years. That was the original conception of testosterone. But it was liver toxic.

[Dr. Gabrielle Lyon]

It was liver toxic.

[Shalin Shah]

So that just. That wouldn't work. Right. And that's why they moved to injectables. And if you look at the timeline, then injectables morphed into testosterone, CPNA and ananthate in the 50s, and then it wasn't until the 1970s or so there actually was oral testosterone that was developed that was not liver toxic. The issue there was that it was requiring dosing three, four, five times a day with fatty meals, right. For, for absorption because the half life was so, so short. But it actually got approval in pretty much everywhere around the world except the United States. So the US is the only place that didn't have this tool available. And this was in the 70s. So fast forward another 40 years almost.

[Dr. Gabrielle Lyon]

Do you, was there a reason why it wasn't approved?

[Shalin Shah]

So I think, you know, again, fda, while is the gold standard across most of the world. I think there are, you know, issues at the agency and happy to dive into that later specifically because I think this therapy has been frankly mistreated by the FDA and patients are the ones suffering. But again, so I don't think there's a real rhyme or reason why it wasn't here. I think you can probably find the same for a few drugs across the spectrum. But then again, it was 40 years or so till then an oral testosterone that really cracked the code of, yes, it's bid dosing, which is twice a day. Twice a day. Yes, twice a day. But the food effect has changed drastically. So you don't, for Kaiserrex, for example, you don't need to have a super fatty meal. You need to take it with food, but you don't have to have that 30, 40, 50 grams of fat which most people would never have for a meal. Right. So again, that's fast forward to today. Now you have that tool in the toolbox that I think really, again, it changes the paradigm for where I think testosterone therapy can go.

[Dr. Gabrielle Lyon]

Where do you think it is in. When you think about the understanding for the general population, where do you think their perception is versus what potential realities are for? You know, we hear a lot of things that are actually, Dr. Mo, Dr. Mohakera has really dispelled, for example, testosterone will cause issues, cardiovascular issues. We know that that is not true. There is potentially a role of low testosterone in various different problems like metabolic syndrome, the list goes on osteoporosis, depression. But from your perspective as someone who is really trying to bring Kaisertrex and just testosterone in general to the mainstream, where do you think the barrier?

[Shalin Shah]

So the understanding, I think if you look at, you know, look at the whole pie, right. I think if you look at half the folks out there, they don't know anything about testosterone at all. So even the male population understanding that it's a vital hormone to them, I think 50% of the population is unaware of it. I think 40% of the population still carries these misconceptions, whether it is the cardiovascular risk, the prostate cancer. I mean, even urologists and cardiologists still have hold on to some of these notions, whether they were frankly trained a long time ago or haven't kept up or again, we just get rooted in these notions. I think that is 40% of the people and then maybe 10%, I think actually understand. And those are maybe a lot of the folks that listen to your show or see great physicians like yourself to help not just feel better and live a better health span, but really want to improve their underlying metabolic health. I think that's 10% today, maximum.

[Dr. Gabrielle Lyon]

Why do you think that there are such huge barriers? Do you think it's an education?

[Shalin Shah]

Absolutely. An education issue. Again, you have to. Testosterone has been around for almost 100 years. And you just have these periods where I think the public and the medical community have been, I don't wanna say.

[Dr. Gabrielle Lyon]

Scared, but definitely scared.

[Shalin Shah]

Scared.

[Dr. Gabrielle Lyon]

Even as providers, I would say that if you are not in andrology, which is again, the study of, or in part the study of sex hormones, especially testosterone, and someone who's been doing it, then you've been afraid, right?

[Shalin Shah]

Yeah. And you have such little training. And again, it's changed. So I think there have been small spurts where I actually liken it to GLP1s today. Right. Every two weeks you will see a new research paper that says, I think GLP1s are useful in this indication or that indication. I think testosterone actually had some of those silver linings. And then again, it's been mixed up with a lot. And even in 1990, Congress scheduled testosterone as a controlled substance.

[Dr. Gabrielle Lyon]

Do we know why?

[Shalin Shah]

So this was really an outcry to Olympic doping. I think, you know, you had other countries that were using this more, and that was a disadvantage for the US and there's public outcry. So there was actually, at the time, it's very important to know the FDA opposed it, the DEA opposed it, the AMA opposed it. So they did.

[Dr. Gabrielle Lyon]

They opposed scheduling making testosterone scheduled. And for listeners, scheduling the drug makes it difficult to acquire. There's just barriers to being able to get the drug.

[Shalin Shah]

It changes the perception immediately. Right. Because again, controlled is bad.

[Dr. Gabrielle Lyon]

Right.

[Shalin Shah]

And then, yes, it is an issue for providers across the board to get access to these medications. And that basically limits the amount of people will be on therapy.

[Dr. Gabrielle Lyon]

And there was an uproar about it. The ama, they opposed.

[Shalin Shah]

Everyone opposed it. Yeah, exactly. The letters, everything was written. So this was it. Was interesting enough, it was actually Joe Biden in 1990 that led that charge.

[Dr. Gabrielle Lyon]

That is fascinating.

[Shalin Shah]

So kind of we've come full circle here for sure. And I'll talk more about it later. We are launching a nonprofit that descheduling is a core tenant of or mission.

[Dr. Gabrielle Lyon]

Of what that nonprofit is going to do and when. It wasn't scheduled up until the 90s.

[Shalin Shah]

Correct.

[Dr. Gabrielle Lyon]

Which means someone could go to their physician's office and say, I would like to try testosterone and I would like to try it in an off label use. I think still 80% or so of testosterone usage is off label.

[Shalin Shah]

Most use is off label. And here's again, fascinating part of the history. So until around 2014, there was in testosterone labels, the indication actually read for primary, secondary, and something called idiopathic.

[Dr. Gabrielle Lyon]

So what that means idiopathic hypogonadism.

[Shalin Shah]

Exactly. So what that means is that we don't know the reason why you have this condition, but you have it. So we should, again, we should treat it just like pretty much every other condition. You think about high blood pressure, you think about cholesterol, you think about depression. Physicians don't. Again, root cause is great to know, but at the end of the day, we also need to attack what's going on or treat what's going on. So that is the standard practice of medicine. Right. But in this instance, testosterone has been singled out and that has been removed from the label. So you. Unless.

[Dr. Gabrielle Lyon]

Wait, what do you mean it's been removed from the label?

[Shalin Shah]

Idiopathic.

[Dr. Gabrielle Lyon]

Yeah, just randomly. They decided to.

[Shalin Shah]

Because the FDA does not like testosterone. Controversial statement. FDA does not like testosterone. So they pulled it and they said, let's make it harder to get. So let's make this physician who knows this patient should be treated jump through hoops.

[Dr. Gabrielle Lyon]

Yeah.

[Shalin Shah]

So not only do you have that controlled problem, you also have this label issue. Again, it doesn't. At the end of the day, you know, clinicians have the right and judgment and they can do that. But it adds to this issue around the whole therapy.

[Dr. Gabrielle Lyon]

It does, it does. And if we were to define low testosterone levels, they seem to continue to move the needle goalpost lower and lower.

[Shalin Shah]

Absolutely, absolutely. So as recent as I think this was 2017, LabCorp's reference range, the end of the bottom of the reference range was something like 320, 340 nanograms per deciliter. That was the bottom and considered the cutoff. Now, I believe that number is around 268. Right. And even I've seen some reference ranges drop to 222.

[Dr. Gabrielle Lyon]

Yes.

[Shalin Shah]

Right.

[Dr. Gabrielle Lyon]

And that is considered, quote, normal within range.

[Shalin Shah]

Exactly so. And again, you know this because of the way that you practice, but reference ranges are really a reflection of our population and I think everybody knows our population is not healthy. So at large, so we are, you know, our goalpost, we're measuring ourselves against something that we should not be or aim for.

[Dr. Gabrielle Lyon]

Yeah. And it's definitely not optimization. If we were thinking of really how do we age well, how do we continue to have a meaningful muscle span, which is the length of time we live with healthy skeletal muscle and able bodied. If we continue to move the goalpost lower and lower and then the other.

[Shalin Shah]

Right.

[Dr. Gabrielle Lyon]

South. And then the other thing is, how is it, and I was looking at some of the guidelines yesterday, how is it that a 20 year old is still within the same reference range as a 65 year old?

[Shalin Shah]

Right.

[Dr. Gabrielle Lyon]

That doesn't make any sense.

[Shalin Shah]

It was really arbitrary when they had come up with it. Right. I think a lot of people in the space akin it to throwing a dart at the wall saying, all right, this is the reference, this is the number you should be. And again, it's variable, just like most other things in your body. Right. We measure glucose in the body and that changes day to day. But whatever you showed up to in that lab is how the physician is going to base your treatment on. And, and here you have something the same. One day you might be 280, one day you might be 300. So I think what we have to do is definitely look at symptoms. That is obviously the most important factor. But again, understanding its role in the metabolic health of a person. And I think now with the advent of oral, you have the ability to still optimize better so you can improve these underlying factors, whether it is cardiovascular health, whether it is cognitive function and so forth. So that's where I think the research needs to be done. Again, these are not indications today, but that's where we know the research should focus on because we know the reasons why low testosterone is bad, that there's thousands of papers puts you at risk.

[Dr. Gabrielle Lyon]

For a multitude multiple diseases.

[Shalin Shah]

Right. And you know, again, big and for big things that are big problems in our societies, whether it's type 2 diabetes and so forth. So we know why low testosterone is bad. We've firmly figured out that it's not risky for cardiovascular disease or prostate cancer. And those studies are unequivocal at this point. Now I think the research can finally be free and say, look, here truly are the benefits that's where really we want to spend a lot of time, is just on the next frontier. So whether that is as a GLP1 combo or.

[Dr. Gabrielle Lyon]

Tell me more about that, because that's really fascinating. The. So Marius pharmaceuticals, do they do other.

[Shalin Shah]

So we are supporting a lot of outside research right now, so we have not launched the trials ourselves yet. I think a lot of this goes back to us working with the FDA and figuring out trial sizes and so forth. But we know there's tremendous interest. Right. So, again, GLP1s, for example, the whole conversation around muscle, well, it's been pretty much front and center. And obviously, yes. Are there a lot of foundational things that you should be doing? Protein intake is super important. Strength training, wholeheartedly agree with these things, but we know population and how they act. So what pharma is doing. And we don't really love ourselves in that.

[Dr. Gabrielle Lyon]

I also think that you should lay the foundation a little bit, because basically, what I want people to get out of this episode, number one, is understanding that they have other options and understanding a little bit about the history.

[Shalin Shah]

Sure.

[Dr. Gabrielle Lyon]

Of how we got to where we are. Because arguably, you know, I believe in testosterone therapy for both men and women. I think that from what I've seen, it's been demonized. Even if a small sector of the population like myself and some other people that are really interested in longevity, believe in it, like yourself and are colleagues at Baylor and various other places, to the large perception, it is still controversial, it is still unobtainable. They feel like it's cheating or, you know, it's almost like saying, if you go on testosterone therapy, that's cheating. But then I would say cheating. What. And if you're a woman, you're going to go through menopause. What is your. So you do hormone replacement, including testosterone, and that's cheating. What, feeling terrible?

[Shalin Shah]

Yeah, no, absolutely. They should not be. You know, folks should not be subjected to these things. I think it actually goes back to testing. Right. Honestly, if you think about testing, frankly, you know, every male over 40 should be tested and every female over 40 should be tested. Right. To understand, you know, what that level is. Because again, more and more. So you're seeing these deficiencies. If it's actually interesting, if you think about your overall health and diagnostic testing these days, testosterone is the single most telling barometer of your overall health, because it's not, again, you think lipid panels or whatnot, your cardiovascular or glucose, you're thinking insulin. But testosterone will give you an insight into your cardiovascular health. Your glucose metabolism.

[Dr. Gabrielle Lyon]

Absolutely.

[Shalin Shah]

Your inflammation in your body. Right. Inflammation is the root cause of almost all disease. So it's mind boggling to me that, that and it's a cheap test. It's less than $10.

[Dr. Gabrielle Lyon]

Yeah.

[Shalin Shah]

And yet if I were to walk into my primary care and say, hey, can you test my testosterone? They say, why?

[Dr. Gabrielle Lyon]

They definitely would. That's wild. And I will give you some statistics. 40%. Approximately 40% of men aged 45 and over are hypogonadal, meaning their body doesn't produce enough testosterone. A U.S. study estimates 190 to $525 billion in health care expenditures over 20 years due to testosterone deficiency. You know, this list goes on. Men with impaired fasting glucose or impaired glucose tolerance typically have hypogonadism. Again, low testosterone. I mean, again, this list goes on. And it's not just for men. It's also for women. Women seem to be under studied when it comes to testosterone. And I will also say this is interesting. It says a lifetime risk of progression from prediabetes to diabetes is as high as 74%.

[Shalin Shah]

Right. Yeah. No, it's, you know, so that's why I say the research is really clear and it's been repeated and reproduced over and over again. And there's, you know, the papers are also there that testosterone deficiency or low testosterone will result in higher all cause mortality, full stop. Right. Like there's nothing more greater than saying, hey, you will die sooner if you have testosterone deficiency. And that has effectively been shown in the research and the literature. So again, testing, understand if there's an.

[Dr. Gabrielle Lyon]

Issue, where do you think we could go with, do you think that there's any chance that we'll be able to put a more reasonable guideline together? Meaning, and I understand that you're not a practicing physician, but again, you are in the business of bringing this to market, which is critical and we need that. We need people that are willing to fund research so that someone like Dr. Mahakera or Lipschultz can go out and do this and gather this kind of data or Rachel Rubin, our friend Rachel Rubin, do you think that there will ever be a time and again, this is your opinion, that we can change the, you know, the values, the numbers of where, you know, is low testosterone in men really 220 nanograms per deciliter? Is low testosterone in women really, you know, free testosterone really normal at 0.5? You know?

[Shalin Shah]

Right. I think, you know, the optimist in me is saying, yes. Right. I think we are sort of Entering this renaissance of hormones.

[Dr. Gabrielle Lyon]

I've never heard that before. You said that we're entering this hormone renaissance.

[Shalin Shah]

Absolutely. Because if you. I mean, just take the female side, right. Pre whi, there were 40% of women were on hormone therapy, menopausal women. 40% of women pre whi were on.

[Dr. Gabrielle Lyon]

The Women's Health Initiative.

[Shalin Shah]

Yes, exactly. Which the study we know is total garbage. Been debunked, retracted everything. Right. But now because of that, still, 22 years later, there are 1.8% of females in menopause are on hormone therapy.

[Dr. Gabrielle Lyon]

Wait, wait. This is so important. We have to take a pause. 40% of menopausal women were on hormone replacement therapy up until the Women's health initiative.

[Shalin Shah]

Correct. 2002.

[Dr. Gabrielle Lyon]

2002. And then the Women's Health Initiative came out and talked about how dangerous estrogen and progesterone. I don't know how much they talked about testosterone.

[Shalin Shah]

They did not talk about testosterone. It was mainly synthetic progesterone and estrogen. Estrogens.

[Dr. Gabrielle Lyon]

That was a primary bit that for 20 some years completely destroyed the public perspective as well as the physician perspective.

[Shalin Shah]

Absolutely.

[Dr. Gabrielle Lyon]

Of using hormone replacement.

[Shalin Shah]

Decimated.

[Dr. Gabrielle Lyon]

Decimated. So it went from 40% before the women's Health Initiative to. What did you say?

[Shalin Shah]

1.8% today.

[Dr. Gabrielle Lyon]

That's disgusting. Yeah, 1.8%. And so now we're backfilling all this information of the positives of hormone replacement.

[Shalin Shah]

And I think, you know, again, how do we change these things? Your question? I think patients, that's why we spend a lot of time trying to educate and we really want to empower patients. Right. I'd love for the medical community to come along and there is again, like a percent that is doing it. But I think the patients have to be advocates for their own health. And how do we arm them with the right information so they can go and do that? Because not everyone is going to go to a functional care doctor or integrative medicine and whatnot. They're still going to their primary care or urologist and so forth, or their ob. Right. And they have to advocate for themselves. So I think it's critical for us to educate them. And I think that will help as backwards as it seems, that will help the societies get along and change the guidelines over time because they. They will see and believe it more. Right. They'll reluctantly maybe start. And I think that that tide will shift.

[Dr. Gabrielle Lyon]

And how is Marius different than, say, quote, Big Pharma? How would the person who's listening think about Big Pharma versus various Other pharmaceutical type initiatives.

[Shalin Shah]

Sure. I mean, I think it even starts with, with Kaisertrax in itself. Right. Kaisertrex is, is aimed at a, at a problem that is large. Right. Even just, again, let's just say for what.

[Dr. Gabrielle Lyon]

So we know that 40% of men over the age of 45 have hypogonadicism.

[Shalin Shah]

Correct. So you're in 20 to 25 million men easily. And then again, you, you think about the female population, again has to be researched and indicated for so forth. But I think the numbers are quite staggering. So what we've seen is this trend of big pharma focusing on rare disease. Right. And rare disease is important, but why? It really comes back to the way our system is set up and frankly, reimbursements. So it's a lot easier to get reimbursed for a rare disease drug than it is a mass market drug. So that's really where the calculus has been over the last, let's call it two decades. And I think. So we, again, we saw this as a mass market problem, but not as an issue around reimbursement, to be honest. We thought this helps people, it will do well. So that was part of the reason that we actually forego the insurance path. Working with pbm, signing insurance contracts. We said, hey, this product should be cash and let's make it accessible to as many people as possible.

[Dr. Gabrielle Lyon]

And big pharma, when one hears the term big pharma, is there a standard definition for that?

[Shalin Shah]

I don't think there's a standard definition. I think there's. Obviously you can look at the size of the companies and so forth, but again, for us it's. We really consider ourselves different because I think this is more on the disease prevention side. Where can we, where can we come and help the healthcare system? Right. We want to save dollars to the system, which is frankly here in the U.S. one, one day away from imploding. Right.

[Dr. Gabrielle Lyon]

So one hour.

[Shalin Shah]

Yeah. One hour. We're minutes away from this. Right?

[Dr. Gabrielle Lyon]

That's right.

[Shalin Shah]

So how do we save this system and actually pull dollars out for the benefit of, I mean, patients, providers and again the country, if you will.

[Dr. Gabrielle Lyon]

And who. Can you tell me a little bit about how the oral testosterone is absorbed? So it's lymphatic absorption.

[Shalin Shah]

Yes.

[Dr. Gabrielle Lyon]

Also the length of time that it stays in the system. Right. So there's cypionate propionate. There's, you know, they seem to have various half lives.

[Shalin Shah]

Correct.

[Dr. Gabrielle Lyon]

What would be. And also just the impact of oral. Oral seems to not raise blood pressure as much as an injectable would. And it seems to have less of an impact on hematocrit, things of that nature, and maybe even potentially fertility.

[Shalin Shah]

Yep. That is. Again, we're running a study there. I think that data is going to be. There's an abstract being published in October 2024. We'll see the full results in 25, but the data is pretty encouraging. So we're excited for that to be announced. But in terms of how it works in comparison or again, by itself, daily oral is taken daily. Right. And that's actually twice daily right now. So what we see is.

[Dr. Gabrielle Lyon]

Which is great. An improvement from three to four times.

[Shalin Shah]

Exactly. Yeah. From previous versions and whatnot. So this is. This is definitely rather convenient for men. Right. We live in a society, we're pretty used to taking pills. We're usually taking a number of supplements. So everybody has their, their box that they're getting ready at the beginning of the week and, and, or traveling with it and, and so forth. So the half life, what we see is around five, six hours. Right. And then usually you take a dose in the AM and you're taking a dose in the pm. What we're seeing is that.

[Dr. Gabrielle Lyon]

And what's the total milligram dosage?

[Shalin Shah]

So there's a range of doses that are available to titrate depending on if that patient is a super responder or where they fall in the spectrum in terms of response. But most commonly we see 400mg bid.

[Dr. Gabrielle Lyon]

And it's important for people to understand that is not the same as injecting.

[Shalin Shah]

Correct. You cannot sort of just equate what Kaisertrex is doing to an injection in terms of the quantities. Right. Because again, this is being delivered through your small intestine. And bioavailability differs. But ultimately you look at the result in the labs. Right. But what we're seeing or what we're starting to understand is that because testosterone is produced on a daily basis anyway in your body. Right. That's the circadian rhythm. When you go to sleep, you're obviously producing your hormones and that's peaking in the morning and going down throughout the day. The closer you can mimic that without going to supraphysiological levels and. Supraphysiological. What I mean by that is then, you know, often injections take you to. It could be. Actually post injection data would show you could be at 3,4000 nanograms per deciliter just immediately post injection. Right.

[Dr. Gabrielle Lyon]

Everyone would. I'm sure all the guys would love that.

[Shalin Shah]

Yeah. But we don't want to do that.

[Dr. Gabrielle Lyon]

No, we don't want to.

[Shalin Shah]

We don't want to do that. I'm sure it's a great feeling too. Yeah.

[Dr. Gabrielle Lyon]

I don't know to ask Matt. Matt the producer. I'm just kidding.

[Shalin Shah]

Yeah, it's. And again, as more folks are using this, you want to reduce the chance of error, but by reducing these high supraphysiological levels for extended periods of time. What we see in the data for Kaisertrex is say the hematocrit, for example, sub 2% of our patients developed a hematocrit level above 54. And then also that was being. If you down titrate, that was solved for. And if you look at some of the real world data and we have abstracts being published on this as well, you can also take a patient that has high hematocrit and then they can lower that by switching to an oral from an injectable. Exactly.

[Dr. Gabrielle Lyon]

Which I think is a real benefit because we know that injectables increase hematocrit. And that's the one thing where people don't necessarily want to go donate blood. It's a bit of a hassle. They might not. Again, some people feel great, some people don't. But if we can avoid that, then that's wonderful. And also travel. We have a lot of guys that travel. And also I definitely want to talk about women. The idea of an. And my husband. Am I allowed to say this was in one of the studies for Kaiserkra.

[Shalin Shah]

Please share.

[Dr. Gabrielle Lyon]

So I have wife clearance, so I'm allowed to say all the things I don't know. So yes, he was. And he loved it.

[Shalin Shah]

Right.

[Dr. Gabrielle Lyon]

And he found it super convenient. And how he did it was he would take it in the morning with a meal and then he would take it in early afternoon as opposed to take it in the evening. And he felt great. I don't know what dose he was titrated up to, but I do know that his levels were considered more optimal for him. And I think he personally sits around 900, which is where he feels great. So I'm curious as to 400 milligrams, it goes up to 400 milligrams twice a day.

[Shalin Shah]

Correct.

[Dr. Gabrielle Lyon]

Do we know, because absorption is variable. Do we know if someone is on 400 twice a day, how much of an increase we would expect? So if someone is, let's say they're at 300. I'm sure you have hyper responders that would go to 6 or 900.

[Shalin Shah]

Correct. So even at a slightly Lower dose, on average, if you take your hypogonadal male, and this is data from our phase three. So they would probably be on average at low twos. Right. Their C max would actually be in the nine hundreds. So, you know, you have that seven hundred.

[Dr. Gabrielle Lyon]

That's amazing.

[Shalin Shah]

Roughly point increase to C max. And again, this is a daily rhythm, right? So you're hitting that on a daily basis, but then at the end of the day, you're going back down to your baseline. So that allows. What we see in the data is that the LH and fsh, right, the signals that are coming from your brain to produce testosterone, are not going to zero.

[Dr. Gabrielle Lyon]

And why is that? And I think this is really important for people listening and especially for the younger population. Fertility is a big thing. And it's fair to say that if someone is trying to get pregnant or wanting to have a child, that they should not be on testosterone replacement therapy. I will also say that people feel really terrible when they are coming off of testosterone replacement therapy. I mean, there's ways to do it in which you do a titration. But one thing that I thought was really interesting is that it seems as if the oral doesn't affect fertility the same way. Is that fair to say?

[Shalin Shah]

I think that, again, the data will definitely show that. So we're really excited to get that out into the public domain. But I think as a surrogate understanding what's happening to those signalings not dropping, then those obviously affect the sperm counts in those males. So again, the data will kind of play out, but I think we kind of use the analogy of. And this applies for men in general, right? If they're just considering testosterone replacement therapy, we have a factory. It's working, right? Or maybe it's not working so well. So we're deciding to go on testosterone therapy. If you're going on an injection, you're likely shutting down that factory and sending all those workers home. Factory's closed. No, I'm not operational if you're taking oral, because again, using the LH and FSH as the surrogates, it's more like, okay, we're going to shut down some of the equipment, we're going to send some people home, but we're still going to be working.

[Dr. Gabrielle Lyon]

You guys are going to have a long lunch hour. Everything is going to be fine.

[Shalin Shah]

Yeah, exactly. We'll bring you back when the time's ready. So the lights are staying on, right? And this actually, even if you're not concerned with fertility, we don't have reports.

[Dr. Gabrielle Lyon]

Of Testicular atrophy, which is also a really big deal. You don't.

[Shalin Shah]

We don't have reports of testicular atrophy. We did not see it in our trials and we did not see it in again, some of the abstracts that will be published in near term.

[Dr. Gabrielle Lyon]

Isn't that amazing? I mean, what were you thinking about this? Because that's a big complaint.

[Shalin Shah]

People are like, it's a huge complaint.

[Dr. Gabrielle Lyon]

So when men go on hormone replacement, they get testicular atrophy. Oftentimes, physicians will use HCG to counterbalance this. This is now another three shots a week or so. And the fact that you would be able to take testosterone without shutting down fsh, lh, fertility, potentially. I mean, I think that probably. I mean, I guess we'll see when the data comes out. But no, testicular atrophy is huge.

[Shalin Shah]

Exactly. Yeah. And again, it's just this is. We're trying to sort of make people understand the importance of the therapy and get treated for the right reasons. Right. So I think it's kind of like Men's health. Men's Health is a bit of an epidemic in its. Right, guys notoriously, don't have doctors. I think the stat is, I think between 18 and 40 or so, you know, at least half or 60% of guys don't have doctors. Because again, most of the issues don't present. But say you bring in libido. Right. If you have. Or ed, if you have an ED issue, you're going to show up at that doctor tomorrow.

[Dr. Gabrielle Lyon]

Right?

[Shalin Shah]

Right.

[Dr. Gabrielle Lyon]

Right.

[Shalin Shah]

So.

[Dr. Gabrielle Lyon]

So if you have erectile dysfunction, you will be knocking at the door.

[Shalin Shah]

Exactly. But that actually, in some sense is a perfect opportunity to say, okay, let's test for your testosterone. Let's see what else is going on. Whether it's your cardiovascular system. Are you pre diabetic? Right. What are some of the issues that are driving to this ed? Right. So I think I actually, for providers and patients, like, this is the best way to take charge of your health. Again, recognize this and then go in and then again, advocate, understand what you should be asking for. So at that point, again, ED is a vascular issue. Right. So let's kind of address some of.

[Dr. Gabrielle Lyon]

These issues, which could also be a metabolic issue.

[Shalin Shah]

Absolutely.

[Dr. Gabrielle Lyon]

Right. When you think about what are the issues that create an atmosphere of erectile dysfunction, Low libido, low testosterone. You know, in my mind, it definitely will start with metabolic dysfunction. I mean, maybe does it start there? Is it the chicken or the egg? You know, either way, it has to be addressed.

[Shalin Shah]

But yeah, again, I Believe it's there. Right. I think that metabolic syndrome dysfunction just is so core to what's going on in this country and globally. And it needs to be, again, it needs to be discussed more and what are the markers for it. So if we're able to bring those things to light, I think folks will be able to pay attention and treat them appropriately.

[Dr. Gabrielle Lyon]

You know, and speaking of this idea of metabolic profile, so there's many studies showing testosterone therapy has a positive impact on the progression from prediabetes to type 2 diabetes. Improving lipid profiles and reducing body fat, improving skeletal muscle. Are there specific metabolic benefits of oral testosterone therapy versus injectable?

[Shalin Shah]

So we're still studying this. And I think what's interesting, at least if I look at anecdotally on the anabolic side, right, because of the circadian rhythm matching, anecdotally we've seen better anabolic effects. So folks that have been on testosterone therapy for say, extended period of time see a bit of a diminishing return, right? Whether that's the ANG receptor that's been overly saturated for too long and how it responds, it's a hypothesis. So I think going back and getting that time off, right, that nighttime is that time off, that is.

[Dr. Gabrielle Lyon]

I've never thought about that before.

[Shalin Shah]

It's again, totally anecdotal. But this is something that we definitely want to study more because I think it allows for patients and providers then to say, okay, we can use this as a wider tool in our toolbox.

[Dr. Gabrielle Lyon]

So can you expand on that a little bit more? Basically, testosterone has this diurnal release, meaning typically is released twice a day, follows a circadian rhythm. And you're saying that with the oral testosterone, it is different than injectable and the impact of it almost augmenting. I don't want to put words in your mouth, but augmenting a circadian rhythm seems to have more of a beneficial effect than other forms of. If you're taking it three times a week because you're taking it sub Q, right? Or once at the end, at the.

[Shalin Shah]

End of the day, anything that's not daily is not physiological, right? The term, I'll even say the term bioidentical is used a lot, right? To say, hey, look, this is a bioidentical hormone. But for example, if I'm putting pellets in you for three months, your testosterone is not produced for a three month period that way. Right. So I think is bioidentical.

[Dr. Gabrielle Lyon]

I do think that whether someone is a provider or is a patient or interested in this, this is a very good point that if something is to be, quote, bioidentical, it should match the way in which the body is producing it. And oral seems to be a way in which that makes a lot of sense. I do think that potentially we're going to see more about this idea of circadian biology. And I think if we can do and utilize medications that mimic and ride along with circadian biology, I personally believe that we're going to see more beneficial effects.

[Shalin Shah]

Right.

[Dr. Gabrielle Lyon]

And then, you know, the other thing that I would think about is what about women? How do we think about the utilization of oral. I mean, women use oral estradiol all the time. They've used oral birth control. Where are we at with understanding testosterone for women?

[Shalin Shah]

Sure. So I think it's a super interesting area if you think about it. Right. And not to make this a male versus female, but you go into, you know, you go into a pharmacy and you, you're a male, you have like 30 options to go and pick up, pick, pick your choice. What do you want for testosterone? Right. If you go for the females, there is not a single FDA approved female testosterone. Zero. Right. And that's just an injustice. Right, right. But you know, I think for the female side, what's happened since WHI2 is that providers and people in this space have really understood how important testosterone is in a female body. And actually testosterone premenopausal is at, I think it's 10, 20, 30 times the amount of estrogen in a body. So it is a female hormone. I think we have to get past this notion that it's just a male hormone. It is a female hormone. Critical. And again, if testosterone affects depression in men or cognitive function, if it affects insulin sensitivity in men, if it affects bone health, muscle mass, tau proteins, whatever you want to put out there, in that sense, it has to have similar ramifications for the female. And I think what's happened is that because of guidelines, it's been pigeonholed into a sexual dysfunction issue.

[Dr. Gabrielle Lyon]

Yeah. And that's not hyposexual. So it's typically used for hyposexual desire disorder.

[Shalin Shah]

But what about, you know, the female that's, that's, you know, 50 years old, that has, you know, you know, early onset of osteoporosis. Right, yeah, that. What about them? We know this is important in bone health. So again, total preface that this needs to be studied specifically in these populations. But I think what we need to see, honestly is a thought process shift in the sense that females have testosterone Deficiency as well, full stop. It's not, again, a sexual dysfunction. It's not just one area of indication. We need to understand that they have this deficiency, and we should understand that it likely should be treated. And we can get into, obviously, we can do the work to say, okay, these are the ranges at least, to give guidelines to practitioners and so forth, but let's not put this into a small, small bucket.

[Dr. Gabrielle Lyon]

And then could Kaisertrex be used off label for women?

[Shalin Shah]

Yeah, we don't obviously have an indication for it, so I can't recommend that we are supporting research in this space. So we have investigators that have come to us and said, hey, look, we want to work on a female study, and we think these are the appropriate doses. And they've also gone to the FDA and said, hey, look, this is what we want to do.

[Dr. Gabrielle Lyon]

I mean, we use, and I speak for many of the providers listening and many of the people listening that are women, I'm sure many of them are taking testosterone, which would be considered off label for low libido or even having low levels of testosterone. But I do think that if there is a way to mimic the natural circadian rhythm in men, we should also be offering at some point for women. You know, is something like this, if a provider was looking to offer it to women, is that something that you think will be available?

[Shalin Shah]

So from. Right. As we discussed earlier, right. Providers have 100% clinical discretion in what they do. Right. So there is there, you know, they wanted to take Kaisertrex at 100mg QD once a day and do that. That's totally their discretion. I think you're gonna see, you know, there's this massive menopause movement, I call it, Right. Which is just, you know, fabulous. Physicians that have gone out there and been really vocal around this space, and I think they understand and they talk about how important testosterone is. Right. So female, I mean, anecdotally, I won't describe exactly how she's related in some sense, but, you know, I had a colleague, let's call it, call me and say, hey, look, I just got on. I got back from a girls weekend. Six of them. She's like, five of six of us are on testosterone. And I'm like, wow, that's just. In some sense, it's amazing, right, because you feel better.

[Dr. Gabrielle Lyon]

Yes, yes.

[Shalin Shah]

Like, that's what you're telling me. And so I think it's our job, providers and investigators. And then, frankly, I think going back to that nonprofit that I mentioned.

[Dr. Gabrielle Lyon]

Tell me about this nonprofit what is it going to do for people?

[Shalin Shah]

Sure. So it's called the testosterone project, right? The testosterone.

[Dr. Gabrielle Lyon]

I'm assuming it's about testosterone.

[Shalin Shah]

All about testosterone. Absolutely. But we have three main missions. The first one is testosterone testing. Let's make this standard. This should be. I mean, frankly, the US Preventive task force should say you should be measuring testosterone because that's what's good in preventive task force. Right.

[Dr. Gabrielle Lyon]

Would it be free? Total. Have you guys thought about that?

[Shalin Shah]

Ideally. And I love to talk about free testosterone. Right. Because as a concept, that's really what we need to be talking about because that's all that matters and all that you can use in your body. So I think it should be free. I mean, ideally, we look at total T, we look at free T, we look at shbg. And I'll definitely get into that as well.

[Dr. Gabrielle Lyon]

Yeah. Because I'm curious, does SHBG go down with oral?

[Shalin Shah]

So uniquely, SHBG drops by. In our phase three studies, SHBG dropped by 30%. In some of the abstracts that we're seeing published, this can range up to 50%.

[Dr. Gabrielle Lyon]

So we have to take a pause because I think that this is a really important concept. Sex hormone binding globulin is a protein that is made by the liver. And here's what happens as individuals age, especially men. We see men and women, we see an increase in sex hormone binding globulin, which then binds free. Hormones are like children. They can't go anywhere by themselves. You need sex hormone binding globulin to walk around with them. And the issue with that is it binds free hormones. When you go on birth control, sex hormone binding can, or, or birth control or even estradiol, anything oral seems to elevate sex hormone binding globulin for a lifetime, which is a problem.

[Shalin Shah]

Right. So massive for, for, for birth controls, like that's a, I guess I don't want to say ticking time bomb, but that's just huge, huge issue.

[Dr. Gabrielle Lyon]

If you then can no longer access the hormones that you're making, what you're telling me is that this oral formulation can actually lower sex hormone binding globulin. To me, that's, you know, in my mind, I'm thinking, well, gosh, even if someone wants to use injectable, I would say, okay, if we measure your sex hormone binding globulin and your SHBG is elevated or higher, and when I think about elevation, whether it's between 60 or 80, to me, that's on the higher end. You know, I'd Love to see that lower. Would someone be able to administer an oral testosterone to lower that?

[Shalin Shah]

Absolutely. So, and again, I think you're just seeing it more prevalent, whether it's with age, some lifestyle things, even alcohol use. Right. Has seen SHBG levels rise and I think that's probably part of the issue even with the younger male too. But yes. So we uniquely take down SHBG and then what that does is allow the testosterone to be used. So free testosterone as we refer to it, goes up. Phase 3, study 2x. In abstracts we've seen closer to 3 to 5x. So this, that's wild. And again, so what's really interesting in this new paradigm of testosterone therapy is we can see testosterone through oral rise to let's call it mid normal levels. Right. Maybe you'll on Average get to 7, 800, right. 900. But your free T goes up preferentially. So the ratio of total T to.

[Dr. Gabrielle Lyon]

Free tea is better than it would be on an injectable or something else.

[Shalin Shah]

An injectable will, you'll take your total T up. Right. So you might go up to 1200, 1500. So that free T level might be the same then. But then you're also dealing with what are the consequences of having your super physiological testosterone for a longer period of time.

[Dr. Gabrielle Lyon]

That's amazing. What would be some reason a contraindication for men or women who are thinking about changing up the way in which they utilize testosterone?

[Shalin Shah]

I mean frankly, as a comparator, the contraindication would be like you don't like taking a pill. Okay, there's, there's, there's, we haven't found any.

[Dr. Gabrielle Lyon]

Like would it make sense?

[Shalin Shah]

You can fact check me, you can find. Yeah, I, I can't find a reason why that, that again, unless I'm bo. Unless you, you know, don't respond. Right. Which again our clinical trials, 96% of patients got to normal levels of testosterone, let's call it even, 80 odd percent in real world.

[Dr. Gabrielle Lyon]

So it's interesting. Would it worsen sleep apnea the same way potentially an injectable will would any form of testosterone.

[Shalin Shah]

Right. So would love to again, I'd love to do the research. I think we go back to our daily circadian rhythm. So like if your testosterone is effectively flushed from your body, at the end of the day, the exotic what happens. Right. So yeah, again I think we, I love to call on any provider that's listening and say, hey look, we'd love to run these studies because I think these are all incredibly important points to change the way that this therapy is viewed, what about.

[Dr. Gabrielle Lyon]

I know that it's absorbed in the lymphatics and small intestine. What if someone has Celiacs or some kind of Crohn's or just an inflammatory bowel disease?

[Shalin Shah]

Right. So there is data on this, actually. So there is data around testosterone and Crohn's, ibs, and we haven't seen issues dealing with absorption. So anecdotally, again, we have providers that deal mainly in GI and gut health and have not had reports of saying, hey, look, Kaisertrex doesn't work. We definitely, again, we would love to do the research there because at the end of the day, like we talked about, you know, our bodies are inflamed and most diseases is caused by this. So if we can take down things like your CRP and your IL6 and so forth, these are all inflammatory markers. Right. If we can take those things down, there's a good chance that you can help some of these things.

[Dr. Gabrielle Lyon]

Where do you kind of see the oral testosterone being synergistic? Have you thought about. What are things just, just throwing this out there? Because I think it would be interesting. Do you think that there's some kind of synergistic effect of if we're going to make oral, you know, or you already have, are making Kaiser tracks, could there be some other synergistic oral compound potentially that one would use?

[Shalin Shah]

Sure. I think like we, we see it initially with other therapies. Right. So like take for example, GLP1s. Obviously, you know, this is a huge topic of today and, and a lot of people listening are, are familiar with them by now. But, but muscle loss is, again, I'm sure, you know, you've talked about, right. To understand.

[Dr. Gabrielle Lyon]

Never talked about that. We don't even talk about muscle on this podcast. No one is, no one is interested in muscle.

[Shalin Shah]

We need to, we need to definitely bring it up. But I think outside of all of the things that one should be working on, so with a partner of ours, they've launched a study to look at what muscle preservation is on. Semi glutide by itself versus semi glutide and cosmetics.

[Dr. Gabrielle Lyon]

I mean, that's amazing because again, I.

[Shalin Shah]

Go back to pharma and they're looking at a lot of these assets that are frankly all the rage. To say, look, we know this is an issue. How do we work on this? Whether they're myostatin inhibitors or whatnot, but these are all early stage assets that honestly at one time or another had.

[Dr. Gabrielle Lyon]

Been discarded when you Say early stage asset. You mean Kaisertrex would be.

[Shalin Shah]

No, no. So these are like for muscle preservation. Like lilies of the world have partnered with other companies that they're like phase two or maybe even earlier. So these are probably three, four years away from an approval.

[Dr. Gabrielle Lyon]

Okay, so basically what you're saying is there's drugs that go through up to phase three trials.

[Shalin Shah]

Exactly.

[Dr. Gabrielle Lyon]

And these are early, early drugs that may have been discarded.

[Shalin Shah]

Exactly. And they may not work. Right. Because again, you have to get through phase three trials where you're in enough of a population. But I go back to testosterone. Being around for 100 years, people know it's safe, they know it works, it's crazy.

[Dr. Gabrielle Lyon]

And then they schedule in 1990, in the 90s, they then schedule it and create a barrier of entry for utilization.

[Shalin Shah]

Correct. And again, as you. Muscle is important. This is not the enemy here. We need to. We're an under muscled country and under muscled population. So how do you again, and a lot of folks talk about how do you make sure you can do the things you want to do as you, you know, health span versus lifespan. Right. Can you put your suitcase up in the plane, Right. Like something as simple as that, or prevent a hip fracture. So sarcopenia, which we haven't even talked about, and again, we have all of these areas that.

[Dr. Gabrielle Lyon]

Let's talk about sarcopenia. Let's talk about do we believe or do you believe or have you seen in the literature that the oral testosterone has a greater impact on certain areas? Maybe more so than inject. Well, again, all testosterone. I believe all testosterone is beneficial.

[Shalin Shah]

Sure.

[Dr. Gabrielle Lyon]

I know that there may be a uniquely beneficial fertility preserving aspect of oral. Do we feel like there are other, or do you think that there'll be other emerging data that this formulation of the way that this delivery system is done because of actually this really diurnal administration?

[Shalin Shah]

Right. So I think like you said, it will come back to that and I think we will see as we continue to do that research, we will see, call them very interesting effects on that population and again, various populations. Right.

[Dr. Gabrielle Lyon]

Wouldn't it be fascinating if the impact on skeletal muscle was greater because you're able to influence muscle clock genes?

[Shalin Shah]

Yeah, absolutely.

[Dr. Gabrielle Lyon]

That would be phenomenal, I think.

[Shalin Shah]

Yeah. Again, just for patients to be able to really embrace these therapies and put them into their toolbox for. Let's call it longevity. Right. What is longevity? It is that living better and longer. But if you look at the pyramid, it's some of the foundational stuff. Right. You got to Eat well, you got to exercise, you got to sleep and manage your stress. I mean, mental health, this is a huge, huge issue for both male and female, but again, it's often ignored. So I'll just talk about that for one second. Again. Our best friend Moekira did an amazing paper on, on depression and low testosterone, where he found this was about a thousand patients, so not a small number by any means. 92% of patients had depressive symptoms, low testosterone. Almost 20% of patients had moderately severe depression in that analysis. And actually that moderately severe group, I think that went from it was 17 and change down to 2% after three months and 12 months of testosterone therapy.

[Dr. Gabrielle Lyon]

Isn't that crazy?

[Shalin Shah]

Huge Again? And that's why, as I said when we started, all these things are intertwined. Go back to testing, right? If these folks or men or women were just tested, right. You would understand this and then you would have a better approach to their treatment paradigm. Right? And we know SSRIs are out there, and I'm sure they've helped a lot of people, but they're not the end all, be all by any means. So how do you make sure, like, what, what, what's the root problem? Let's find out what's going on there.

[Dr. Gabrielle Lyon]

And how do you guys plan on educating the public? I mean, you're doing this. I mean, this is really. I'm so glad you're willing to come on and so glad you're willing to support the podcast, because it's needed. But how else? So the, the podcast, educational outreach, do you guys have a game plan for that?

[Shalin Shah]

So, yeah, I mean, again, it's really just, it's. It's kind of a full court press on all outlets. Right. Obviously, you have your channels through traditional pr. You have new media like this, social media. I mean, rethinktestosterone.com that's our disease state website. And all we do is look at these literature and these studies and bring light to them. Because what we've seen, at least in our journey, is that the research has been tremendous. So I think on a previous podcast, you had mentioned the Androgen Society, right? Great, great minds, all focused on andrology, and folks like Abe Morgan Taylor, who we work really closely with since Inception, and he's been doing this for probably 40 years. Right? The data is so good, but it's kind of lived in a vacuum. And so we've kind of said, okay, let's take the next step. We need that microphone to Testosterone Project. As a nonprofit, our goal there is Obviously using science as our foundation, but we see this as being a million patient strong advocacy group.

[Dr. Gabrielle Lyon]

So what is the testosterone project gonna do?

[Shalin Shah]

Those three things we're gonna look at testing. Second is gonna be female testosterone. So how do we go to the FDA and say a trial for females should look like a male trial? We shouldn't have these onerous expectations or thousands and thousands of patients that need to be trialed. Because we know that's why folks have stayed away from this, because they've made it infeasible to run these studies even though the data exists. Right. We know it's good. We know it works. Why are they, you know, why are they holding ground? Right. Again, Traverse should have. Frankly, the FDA should have came out already and changed the label. They should have fixed the label. They did it. They asked for traverse and then traverse trial.

[Dr. Gabrielle Lyon]

Traverse trial was the trial that looked at the impact on cardiac. There was multiple arms.

[Shalin Shah]

Multiple arms, prostate, et cetera. Main one was cardiovascular. Right. 5,000 patients, gold standard randomized placebo controlled. Right. This took seven years and hundreds of millions of dollars because the FDA said, hey, look, you have to do this. And so they should actually, frankly, they should have came out already and changed that label, but they haven't. So I think, again, we are. Marius is taking steps there. But I think the testosterone project is really for patients to say, hey, look, we have a voice here. And what you do, the decisions you're making are impacting our health.

[Dr. Gabrielle Lyon]

Yeah, Right.

[Shalin Shah]

So the third point in that is descheduling testosterone.

[Dr. Gabrielle Lyon]

Because how long do you think that. Have you talked to our colleagues? How long do you think that. That. How does something like that even happen?

[Shalin Shah]

Sure. So we're pretty. Yeah, no, it's a good question. Right. So we're Fairly active in D.C. right. Again, if you asked me seven years ago, would I say, hey, I'd be, you know, going lobbying Congress every month and trying to, you know, move. Move the needle there? No, absolutely not.

[Dr. Gabrielle Lyon]

And how does that work? You just go, you show up, you say, hey, man, it's education. And by the way, have you ever tried. You know what you should do? You should put in the water.

[Shalin Shah]

Yeah, absolutely.

[Dr. Gabrielle Lyon]

You should put in their water. And then have you just been feeling so amazing lately?

[Shalin Shah]

Absolutely. I invite any member of Congress or anybody in the Senate to call us and get on Kaisertrex, because I think, again, frankly, patient stories, understanding what this means. Right.

[Dr. Gabrielle Lyon]

So how to make this on schedule? Do you have to go to Washington? What does someone do?

[Shalin Shah]

So it's a combination Of, I think, congressional support and understanding. Again, this is good for patients, people. Again, at the end of the day, Congress represents people, right? So that's why the testosterone project, as a patient advocacy, can speak to them. If we have a million patients, or half a million, whatever that is, coming and saying, hey, look, here's the data, here's the science, and that's the beauty. We're not shooting from the hip. It's so supported. And you take that and you say, look, why don't you. Let's pay attention to this. This matters, right? We talk a lot about insulin prices and so forth. That's one healthcare topic. And access and all these things. But this isn't, this isn't, let's call an easy thing, I think, for them to get behind. So then they have to work with the agencies, right? The fda, the DEA controls it because they control scheduled products. That falls into their peer purview. And then the FDA is of course going to opine as well. DE is not a scientific agency. So FDA is going to opine, and that's why we're asking the FDA be scientific. This is not 20 years ago, this is not 30 years ago. We have the data that says what's safe?

[Dr. Gabrielle Lyon]

We are hearing over and over again that testosterone is safe for men and women. When it comes to telemedicine, right? There's an increase in telemedicine clinics, telemedicine practices. Do you think that that's breaking down barriers to access or. Barriers to access? And where does Kaisertrex fit into that scope?

[Shalin Shah]

Absolutely. So I think telehealth is breaking down barriers. It's a much needed solution in our system. I mean, look, in this country, we already have a shortage of doctors, right? That's. That's just bar none, we have a shortage of doctors, and then we have a shortage of specialists, especially hormonal specialists, right? So, you know, as we talk about patients and they're seeking help, where do they go, right? I think if everybody could go to their provider or their current provider and have that sort of. That's called tlc, right? I mean, the system is set up that a provider has seven minutes with you, right? How in the world, for a society.

[Dr. Gabrielle Lyon]

That erectile dysfunction, go, yeah, yeah, like.

[Shalin Shah]

You got all these issues, right? How can you go over them and take control of your health? It's impossible. So I think, I think telehealth provides an outlet for these patients. I think there will be in all sort of new areas, right? There's a spectrum of providers, and I Think there's going to be your great holistic providers down to the folks that maybe shouldn't be there. Right.

[Dr. Gabrielle Lyon]

Yeah.

[Shalin Shah]

The beauty is that that's why we have a regulatory system and those can be addressed. But at large, if it takes six months to see a urologist or endocrinologist who may or may not actually still.

[Dr. Gabrielle Lyon]

Be good, it's actually really tough. It's really tough. So if I as a provider or even as a patient say, okay, someone comes to me and says, let's put it from a physician standpoint, my patient comes to me and says, you know what, Gabrielle, I have been reading about Kaiser tracks. I want to take it. How do I as a provider go about prescribing it or what do. What is the interaction with that patient?

[Shalin Shah]

So for you as a practicing physician provider, that's relatively easy. We have pharmacies that are set up, mail order pharmacies, so it's not going to be sent into your cvs. We have set the distribution network and such to basically control the pricing so it doesn't get high for the patient. $159 if you send it to there, which is frankly the copay for a.

[Dr. Gabrielle Lyon]

Lot of people's drugs anyway, which is amazing.

[Shalin Shah]

So yeah, I think that's very, very reasonable. We do have some, let's call it concierge practices or there's testosterone programs. What you see today often are bundle programs. So maybe it's the physician visit the labs and Kaisertrex. Right. That might be 199 bucks a month. But that's, I think there's tremendous value in. Now again, physicians can either send it to a mail order pharmacy or they can create.

[Dr. Gabrielle Lyon]

And when they go to the Kaisertrex website too. So if there's physicians listening and they're like, wow. Which I really strongly recommend. And again, I'm not giving medical advice. I just. The go goal is to hear, educate. A lot of providers listen to this podcast. I strongly recommend they try it for their patients again. My husband tried it. He's still taking it and it just was so much easier for him. Some guys don't like needles and the gels. We have two little kids. I didn't want him using any kind of gel preparation because I didn't want to get it on our kids.

[Shalin Shah]

Right.

[Dr. Gabrielle Lyon]

So if someone is interested, they would google kaisertrax.

[Shalin Shah]

Yep. Kaisertrex.com right. For the physician, they can go to the provider side. There's a clear link how to get it. And there are our pharmacy partners. So we have a couple pharmacy partners. Depending on how your practice is set up, one will fit it. No matter how you're currently doing it. One of our pharmacy partners will fit the way that you're practicing.

[Dr. Gabrielle Lyon]

Just out of curiosity, what is the dosing? So the highest dose is 400 twice a day. What are some of the other dosing?

[Shalin Shah]

So then the other two most common doses will just step down to 300mg bid. And then you'll have a 200mg bid.

[Dr. Gabrielle Lyon]

Okay. And let's just say I know that it's not FDA approved, but let's just say someone were interested in. So the 300 or 200, how could we think about that? Not. I mean, obviously it's not the same as an injectable.

[Shalin Shah]

Sure.

[Dr. Gabrielle Lyon]

But would that be, for example, when we think about giving testosterone to a woman based on an injectable. Right. It would be maybe we would give them maybe 5 milligrams, whereas a male, we might give 100 to 200. How would we. Or is there a way to think about it?

[Shalin Shah]

Sure. So usually see like a tenth of a dose. Right. That's kind of the rule of thumb. So, you know, right. If we, we have 800 milligrams is a common male dose. You do have 100 milligram capsule. That is, you know, so it's 1 8. It's not exactly. But it's 1/8th of a 4. You know, that could be, I guess a female dose. We are again supporting a study that is actually going to look at a 50 milligram dose. So that's going to start as well.

[Dr. Gabrielle Lyon]

That's amazing. And then would that be coming from, would that come from a compounding pharmacy?

[Shalin Shah]

How so? No, no, Kaisertrex is not compounded, full stop. Right. Kaisertrex, you know, again is FDA approved and we have our manufacturer partner for the last 12 years. Right. Since our early studies. That makes Kaisertrex, I guess a good way for the listeners to think about it is it's a soft gel. So it's kind of like a fish oil capsule. Yes. Right. I wish I had one in my pocket.

[Dr. Gabrielle Lyon]

You probably have some upstairs. Let's just check Matthew's bag.

[Shalin Shah]

Exactly. But again, it's like a fish oil capsule, so it would not be compounded. I think that's a good, you know, important point. Important point for patients to understand. It comes directly from us. Whenever it's coming from the pharmacy. You're coming in a one month supply, 120 tablets in that bottle. And that's a one month supply. So very simple.

[Dr. Gabrielle Lyon]

And if someone was interested in getting a smaller dose, like a 50 or 100, they would contact.

[Shalin Shah]

So the 100 milligram dose is commercially available. Exactly. 50 milligrams.

[Dr. Gabrielle Lyon]

Oh, I see. So the 200 is 100 twice a day.

[Shalin Shah]

Well, so no, there's actually a 200 milligram capsule. There's 150 that you take twice with that and then there's 100 milligram capsule. So we have three different capsule strengths to get to those doses.

[Dr. Gabrielle Lyon]

Oh, I see. Oh, amazing.

[Shalin Shah]

Okay, so there's a lot of flexibility there for the provider. Right. Again, depending on how people respond. What we do see anecdotally, often again, injection switches tend to be at that higher dose.

[Dr. Gabrielle Lyon]

So can you give me an example of what it would look like to transition someone from if they were taking 200 milligrams a week?

[Shalin Shah]

So, yeah, if they're anywhere from. If we've seen anywhere from 100 to 200 milligrams test sip a week. Right. Often still, that 400 milligram dose works. So what I'll, what I'll share is actually, so this is again being published in October 2024, but it looked at patients on all on 400mg bid twice a day. And if you look at the efficacy parameters, whether that's total T or free T, you see again the rises that you would expect. But interestingly enough too, on the hematocrit side or the LH FSH side, you don't see hematocrit spike. I think the data will show it won't get above 50 in this patient.

[Dr. Gabrielle Lyon]

Group, which is great.

[Shalin Shah]

It's really reassuring. Right. For both patients and providers. And then again, your LH and FSH don't drop to zero.

[Dr. Gabrielle Lyon]

I mean, that's amazing.

[Shalin Shah]

So they're active.

[Dr. Gabrielle Lyon]

The elevation of fertility we haven't talked.

[Shalin Shah]

About is also the conversion to estrogen.

[Dr. Gabrielle Lyon]

Oh, yes.

[Shalin Shah]

Because that's a big concern for injection patients. Yes.

[Dr. Gabrielle Lyon]

What is the average conversion of testosterone to estrogen if it's injected? I think it's. Do you know the number of estrogens?

[Shalin Shah]

I don't know offhand what the exact conversion is.

[Dr. Gabrielle Lyon]

I have to look. I want to say it's between 6 and 10%. Not sure.

[Shalin Shah]

Right. But often what again comes back to super physiological levels. You have this, you're going to convert more to estrogen. So for us, our testosterone to estrogen levels stay in line. So you don't see folks taking anastrozole. Right. That's often, honestly, with injections. Right. In a lot of places, that's like, comes automatically with your testosterone script and we don't see that. Which I think is quite nice because at the end of the day, estrogen is also an important hormone for the male. It's also a male hormone.

[Dr. Gabrielle Lyon]

Yes, it is.

[Shalin Shah]

Right. So we don't want to take that down or block it.

[Dr. Gabrielle Lyon]

I didn't realize that. That there is less of an estrogen conversion would. Do you think that the oral may be better for people? And I'm just speculating here with body composition issues.

[Shalin Shah]

Absolutely. I think it's a good point. Right. Because again, if you have body composition issues and you're taking a gel, for example, Right. Adipose is filled with that and it's going to convert. So I think that's why we see a lot of sort of obese folks struggle on therapy and then on AIs and whatnot. So. And just the variability in sort of absorption. Right. Yes. I think this provides a great solution.

[Dr. Gabrielle Lyon]

For them because whether sub Q or im, you still have to get through that tissue. I also think that it provides a great solution. Where do you think this is going in the future? Where are you guys hoping that Kaisertrex gets to? Are you hoping that, I don't know, that there's some for men, some for women, that it is easily accessible? Where is it going?

[Shalin Shah]

Yeah, no, good question. So I think it's, it's, it's a bit of both, for sure. Right. Again, we were definitely, you know, we're committed to the research for sure.

[Dr. Gabrielle Lyon]

Which is, you know, Mo always says, follow the science. Follow the science.

[Shalin Shah]

Yeah, absolutely. Because I think we, you know, honestly, in our, in our, we know it's down the right path. Again, the literature, there's no shortage of.

[Dr. Gabrielle Lyon]

Good data, which is why I wanted you to come on and talk about it.

[Shalin Shah]

So we just need to continue to show the story with Kaiser trucks, to be honest. Right. So if you think about the male side, you think about future research in women. And a lot of people ask me this, they actually ask, okay, hey, what's your next product? And I just kind of, I just pause and I say, look at all the things testosterone does. We don't need another product. We need to educate and make sure that, yes, we are doing the research and showing what that is in these different products, populations or different comorbidities. Right. I think that's really where the greatest good will come to the public, is understanding that and then thinking, okay, hey, and also, again, we Want to show it? I'd love to have it on our label for a type 2 diabetic. Or you look at like.

[Dr. Gabrielle Lyon]

I mean, that would be amazing.

[Shalin Shah]

Yeah, I mean, look at that. Look at the sheer number of type 2 diabetics we have in this country or the dollars that are going in healthcare spending because of, of this. Right. So if we could, you know, T4DM. I'll bring up this study. It was done in Australia, probably published in 2020, now, maybe 21 again, thousand patients, randomized controlled trial. And it, and it looked at the progression of prediabetes to type 2 diabetes and it was almost nil progression of that. And then you also look at the reversal of type 2 diabetes down to, you know, a normal glucose, A1C. Actually they used OGTT, which is even.

[Dr. Gabrielle Lyon]

A better metric, which is an oral glucose tolerance test.

[Shalin Shah]

Yeah, exactly. And you kind of scratch your head and you say, well, why is this not being talked about when we have this massive, massive issue? That's why we've actually gotten great interest from countries around the world, or even in places like Saudi Arabia or uae, who have higher diabetic rates than the us, believe it or not, which is hard to fathom, but they have this very high or keen interest on testosterone therapy.

[Dr. Gabrielle Lyon]

Is testosterone therapy, Is Kaisertrex available outside the us?

[Shalin Shah]

So we are available in the UK under early access programs. We have.

[Dr. Gabrielle Lyon]

What does that mean?

[Shalin Shah]

So early access programs are effectively like named patients, so single patients. So say your doctor is aware of Kaisertrex and he says this is the best. He or she says this is the best solution for you. They can, they can get access to it. Right. So it's, I guess, similar to an approval, but there is access. It's actually already, we've already applied for approval, so that's underway anyway. So there will be a full approval likely. In the United Kingdom, we have approved, we've applied for approval in Canada already. And then we're looking at these other countries that again, we've receive strong interest for.

[Dr. Gabrielle Lyon]

And we know Kaisertrax, the only oral available of its kind.

[Shalin Shah]

So in the US there are two.

[Dr. Gabrielle Lyon]

Other products, but they require a lot of. They require, I think, double the dosing.

[Shalin Shah]

So the dose, so the bioavailability.

[Dr. Gabrielle Lyon]

And it has to be with a fatty meal, which I don't really want patients on multiple high fat meals.

[Shalin Shah]

Correct. So, yeah, I think they have their own dosing issues, if you will. And then again, it comes down to.

[Dr. Gabrielle Lyon]

And that's what I've seen. I mean, so that's what I've seen. I've seen barriers to entry in two ways. Number one, the absorption for other forms of oral testosterone require a high fat meal, at least 50 grams of fat multiple times a day. So that's. That's too high. Sure, because then it kind of crowds out for other nutrients, especially dietary protein, and then access. So it's not necessarily easy.

[Shalin Shah]

It cost over a thousand bucks a month for us.

[Dr. Gabrielle Lyon]

I mean, that's insane.

[Shalin Shah]

Exactly. I mean, it's insane. You're not going to get coverage or again, you're going to get.

[Dr. Gabrielle Lyon]

You're not going to get coverage. And I can't ask patients to spend over $1,000 a month.

[Shalin Shah]

Exactly, exactly. That's when, again, you say, okay, you have to use an injection, which is fair and fine, but. So we have these other things. But again, frankly, for us, we think the market is so large, there's just. This is just a massive problem. So we want, you know, the awareness to grow, and I want everybody to do well in that sense. But I think we just have developed, you know, what should be the standard of care for those multiple reasons.

[Dr. Gabrielle Lyon]

Where do you want to see it going? So you want, obviously you have the testosterone project where you want there to be patient advocacy. You want testosterone deschedulized. I totally agree with all of that. You want there to be more research on women in five years from now. Where do you want Kaisertrex to be?

[Shalin Shah]

So I think. And I want it to lead with the science. Right? I think in five years, in five years, if we are successful with that science and education, you could see 10 million men in the US on Kaiser Trax and more globally. But what you're going to see is actually, I love to, over time, show some of the curves that we have around metabolic disease, and I love to start correcting them right through not just Kaiser tracks, but also this mindset of foundational health or preventive health. And I'd love to start correcting those curves. And that, to me, will be tremendous, tremendous success.

[Dr. Gabrielle Lyon]

So meaningful. Well, Shailen Shah, CEO of Marius Pharmaceuticals. This I'm hoping that you'll be willing to come back on when you get some of these papers published and out. What you are doing, I think, is tremendous. I think, number one, you offer a solution. You offer a solution to a healthcare crisis. It is very commonly talked about, this obesity epidemic. It is, you know, very commonly discussed. Cardiovascular disease and Alzheimer's disease. There are two, in my opinion, there are two core problems. This is the problem with metabolism and muscle and feeding into that, whether it's the chicken or the egg, is this problem with hormones. And if we can combine the two, which I think Kaisertrax makes things very accessible. And you guys are so dedicated to education and science that I'm so grateful. So thank you so much for coming on.

[Shalin Shah]

Thank you so much. I'll leave your listeners with a bit of a cliffhanger because you mentioned Alzheimer's. And so the research actually will show testosterone deficiency will lead to an increase in tau proteins. And tau proteins are one of the best indicators we have to the development of Alzheimer's, beyond, you know, obviously the genetic typing and so forth. So this is some area that we are also going to pursue. So I'll leave that as a cliffhanger because we're going to get into it and hopefully by the next time I'm on, we have something to share.

[Dr. Gabrielle Lyon]

Thank you. Thank you so much.

[Shalin Shah]

Appreciate it. Thanks for having me on.

[Dr. Gabrielle Lyon]

The Dr. Gabrielle Lyon podcast and YouTube are for general information purposes only and do not constitute the practice of medicine, nursing or other professional health care services, including the giving of medical advice, and no patient doctor relationship is formed. The use of information on this podcast, YouTube or materials linked from the podcast or YouTube is at the user's own risk. The content of this podcast is not intended to substitute for professional medical advice, diagnosis or treatment. Users should not disregard or delay in obtaining medical advice for any medical condition they may have and should seek the assistance of their healthcare professional for any such conditions. This is purely for entertainment and educational purposes only.