Overcoming antibiotic resistance. Interview with TAXIS CEO Greg Mario

Greg Mario, CEO of TAXIS Pharmaceuticals shares his dynamic journey from a childhood of constant relocations to spearheading the fight against antibiotic-resistant infections. Greg opens up about his immigrant grandparents' profound influence and a transformative experience with a captivating professor at Trinity College that shifted his academic focus from mechanical engineering to chemistry. This pivotal change set the foundation for his career in the pharmaceutical industry, highlighting his adaptability and dedication to human health.

Discover the fascinating evolution of Evogen, a company initially centered on bio and chemical threat detection, which pivoted to tackle central nervous system diseases under Greg's leadership. We also explore the creation of as revolutionary blood-based epilepsy diagnostic test, as well as the pressing issue of antibiotic resistance. 

Greg provides a historical perspective on antibiotics and underscores the urgent need for innovative antimicrobial treatments to combat the relentless rise of superbugs, emphasizing the resilience and adaptability required in the healthcare industry.

In the final section, we explore the relentless pursuit of funding in the biotech world through Greg's experiences with TAXIS Pharmaceuticals. Learn about the company's early days and the recent $2.7 million NIH grant for their promising efflux pump inhibitor, now on the brink of human trials. 

As of March 2025 HealthBiz is part of CareTalk. Healthcare. Unfiltered and can be found at the following links: 

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Host David E. Williams is president of healthcare strategy consulting firm Health Business Group. 

Episodes through March 2025 were produced by Dafna Williams.

Transcript

0:00:00 - David Williams
Before the dawn of antibiotics, infections were often death sentences. With the rise of antibiotic-resistant bacteria, some fear that we could return to those scary times. Fortunately, at least a few organizations in the private and public sector are mobilizing to meet the challenge. Hi everyone, I'm David Williams, president of strategy consulting firm Health Business Group and host of the Healthbiz Podcast, a weekly show where I interview top healthcare leaders about their lives and careers. My guest today is Greg Mario, CEO of TAXIS Pharmaceuticals, which researches and develops treatments to fight antibiotic-resistant infections. If you like this show, please subscribe and leave a review. Greg, welcome to the Health Biz Podcast. 

0:00:52 - Greg Mario
Thanks so much, David. Pleasure to be here. 

0:00:54 - David Williams
We're going to talk about taxes, but first we're going to talk about how you got there and winding it back to the start and ask about you know what was your childhood like? Any particular childhood influences that have stuck with you? 

0:01:08 - Greg Mario
Yeah, well, we moved around a lot following my dad on his career path in pharmaceutical, the pharmaceutical industry, but I think the key influencers obviously my mother and father. We came from pretty much nothing and he worked his way up and he taught us about work ethic and being true and honest. Very important His parents, his mom and dad. His mother came from Holland she emigrated in 1910, I guess and his father came from Osti, Italy, and interestingly, just as an aside, his name was Lidio Amerio. Doesn't that sound beautiful, David? 

0:01:58 - David Williams
Yeah, very nice. 

0:01:59 - Greg Mario
Lidio Amerio. But no, they changed his name at Ellis Island to Jerry Mario. That's why I have two first names. And also church. They were very religious and we went to church three times a week twice on Sunday because that was supposed to be the holy day where family, you know that part of your life would be really focused on. And then on Wednesdays we'd go for a short service and choir practice, and I loved singing in the choir and I must say that I'm not a real religious guy. I believe in God we're not going to get into that topic right but it was so important to me because I was a bit of a troubled child. I had a lot of skills and abilities that I didn't know how to handle and hone, and throughout my life I've learned how to turn them to positive drivers, and that's why I'm here, that's why taxes is here. 

0:02:54 - David Williams
That sounds very good, you know. Speaking of names and name changes, of course, that's, I think, a common part of the American experience. I had a guest recently, the CEO of FibroBiologics, and his name is Pete O'Heeron. O apostrophe H-E, e-r-o-n. Which I'm trying to figure out, like where is that from? And he said it was. He met somebody. I don't know if it was immigration, but it was actually originally a Hearn from Ireland and someone heard it completely differently and they spelled it like that and wrote it down differently, and they didn't even know how to write. 

He's still using it. So say, through that apostrophe and so anyway, all right. So you, um, you grew up and then you, you did go to college, so you're in business school, so you're, you know, conventional enough by. You got to that point. I think you went to trinity, studied biochemistry. What was that all about? 

0:03:42 - Greg Mario
Yeah, that's right. So I actually in high school I never really cared much, except for sports, yeah, and girls. Ok, just be honest. But I had a professor of physics that really captured me and I fell in love with mechanical engineering and a chemistry class and I was good at the hard sciences and math chemistry class and I was good at the hard sciences and math. And so I went to Trinity and I was thinking about being a mechanical engineer and I didn't like the professors. 

I was hanging out second semester, freshman year, and Dr Henry DePhillips, who is the chair of the Department of Chemistry. I took a class with him first semester. He saw me on the quad, beautiful sunny spring day, second semester, and he came up to me and said Greg, what are you doing? And I said well, dr Phillips, I am playing Frisbee and later I'm going to play hacky sack, because that it was gone, physics was out. He comes up to me. He says no, what are you doing? I said I don't really know. He said, okay, here's what you're going to do. He's a left-handed, super high energy guy. He puts his left finger into my chest and he says Greg, who's your advisor? I said I don't know. He's okay, from henceforth I'm your advisor and you will be a chemistry major. And it was almost like that Jennifer Aniston office space moment with a Kung Fu, if anyone knows that. Yeah. 

0:05:19 - David Williams
Okay, okay, okay. 

0:05:21 - Greg Mario
And if it wasn't for Henry I don't think I'd be here right now. I love him. And he pulled me into chemistry and so biochem. And then I was pre-med. I wanted to be a doctor. I was very interested in life sciences. I want to make an impact and use my skills to do something that improves the human condition. That just was in my veins. And I didn't want to go right to med school. I wanted to get a job. 

So I sold drugs yeah, not the kind you want, the kind you need. I worked for Burroughs Welcome and I was very good at it. But I saw that managed care was really coming in. You know, this is like 1990. I'm sorry, 1988, 99. And physician autonomy was being lost and I didn't want to work for some pencil pushing, you know, finance person or accountant. 

So I went to business school, I went to Fuqua, nice, and at Fuqua I was motivated by fear, because I always skated by. I have enough God given skills, decent amount of intellect that I can figure a few things out and put the minimum amount of effort in and get a B. That's all I was going for, just B. And I got to Fuqua and I was like, oh my gosh. You know, these are some of the brightest people on the planet and I was afraid. And fear can be a great motivator for short periods of time, and fear can be a great motivator for short periods of time. It'll wear you down if it's strong. But it got me focused and, you know, I graduated top 10. And I'm very proud of it. 

But, like my dad had told me once, he said you're only as good as your last performance. If anyone says to you, do you know who I am? Yeah, I immediately think no, I don't care, yeah, and then the Janet Jackson song kicks in Dude, dude. What have you done for me lately? And that's the way I lead my life. I'm proud of what I've accomplished. I'm, you know, confident, not cocky. But what's next? Yeahy, but what's next? Yeah, and taxes is what's next. That's what I'm doing. That's what I've dedicated my life to over the last 12 years. 

0:07:34 - David Williams
Sounds good. Well, you know your description of Trinity sounds about. What I remember I was down the road in Middletown while you were up there. 

0:07:41 - Greg Mario
No way yeah. And they called it I think Camp Trin Trin was the nickname for it at the time, by the way, I climbed that chapel probably 100 times. Yeah, interesting A bit of a risk taker. 

0:07:55 - David Williams
Yeah, yeah yeah, so before taxes. I saw a couple of things on your resume MFP and Evogen what were those? 

0:08:05 - Greg Mario
Yeah, so before taxes, I mean this goes back to 2004. I was in pharma. You know a bunch of different companies. Mfp has been around for a long time and that's Mario Family Partners. That is a fund that my two brothers and I and my dad put together and it's primarily for life sciences targeted early stage investments, very high risk. You know portfolio approach, but all you need is one winner, and you know it can be a big winner, and so we've been doing that for a long time. That's MFP. Evagen is something separate. 

I picked up on it to help a friend who was running a business that had some cash flow. It was a threat detection system for bio and chemical agents. They had a contract with the US Post Office spinning off about two, two and a half million of cash each year and they weren't going anywhere with it and he asked me to get involved. I ended up joining the board, becoming chairman of the board. I fired everyone in the C-suite because they were just no good and there's a lot of depth to that discussion, but let's not name any names. It's fine, but I took care of what had to be taken care of and then I hired a guy and he came in and he put us back out of the ICU and stabilized the patient and then I said, ok, we have a choice. We can either milk the two, two and a half million a year, which no one's going to get excited about. We can reinvest it. 

Let's go into central nervous system disease, because that's the Wild West right now. Nervous system disease, because that's the wild west right now. Alzheimer's, you know, parkinson's, als, dementia, you know, it doesn't matter if you live to your 90, if at 80, you don't remember who you are right. So that's where the action is in pharma, and I said we should go there and we took our technology and applied it to some technology at UPenn and Cogbio was born and it's the first ever blood-based epilepsy diagnostic test Right now. It's just suction cups on your head, much like you do with the EKG. They do it on your head for an EEG, without getting too deep. It's very disturbing and the only way they can get a definitive diagnosis is if you're actively seizing and guess what, by the time you get to the emergency room, it's over. Yeah, so now we have something. We can take a blood sample. It has to be within about 48 hours of your seizure and it's very interesting. It's an algorithmic. This is artificial intelligence at its best, where you're looking at a, an array of proteins that are associated with inflammatory neurologic conditions, and and it works. And we're just trying to get to statistical significance. We've got a couple of studies set up. 

I think we're going to make an impact, and my philosophy, just to make it clear 20,000 foot, make an impact, positive impact, thereby create value. Then you get return on investment right. I want to use my God-given skills and talents to do something that, on the day I take my last breath, I can. I can look back and say I, I accomplished something of significance. I don't need my name on the building, like my dad's is Rutgers. I don't need that, but you know what I mean. It's just like I. I take risks that other people think you know is probably illogical, but I can't help it. I'm swinging for the fences and taxes is there and we're going to make it happen and it's going to be huge. 

0:11:52 - David Williams
Oh, that sounds good. Well, you know, when you're talking about epilepsy and the EEG, one of the few advantages of being a bald guy is that it's easier to get the. 

0:12:00 - Greg Mario
EEG reading no, it's true, because they have to shave your head a little bit. 

0:12:02 - David Williams
Yeah, exactly it's that's traumatic for people, but not for me. 

0:12:06 - Greg Mario
Oh, you're too funny. I didn't think of that, david, yeah. 

0:12:09 - David Williams
That's just daily maintenance for me, so luckily I don't have any seizures, though, at least at this point. All right, so let's talk about taxes. So at the outset of that, what is the? How would you think about the issue of antibiotic resistant strains of bacteria, like what? What is the issue? What does that mean? 

0:12:26 - Greg Mario
Well, um, you know, before penicillin that was the number one cause of death infections and it was from bacteria. Um, our average uh life expectancy was 45 to 50, right, and with good antimicrobial control, the wonders of modern medicine were found and advanced. Now our average life expectancy is about 80 something. When penicillin was introduced, you know, we got the ball rolling and there was a lot of activity and a lot of new drugs. But the thing about bacteria is that they were here before us. They'll be here after us. 

They're incredibly resilient creatures and they can live in volcanoes. They can live in anaerobic, no oxygen environments. They are tough and the reason they're so tough is they they mutate. So when they're attacked by something like an antibiotic, they freak out and they start almost a cancerous process and they mutate and most of the mutations kill the cells. But one mutation allows them to be viable in the environment of threat with the antibiotic and then the antibiotic doesn't work anymore. So you need another one, then you need another one and we're always going to need new ones, because you know they evolve and we're running out of them and in some cases, entirely like super gonorrhea, which it's called, there's only one drug that still works and it's at very high doses. 

It's almost outside of its therapeutic window. It's almost like watching baseball, which is back in season season, where they show you the rectangle where that's a strike zone and you got to get in that strike zone and if you're outside of it you're outside. So if you go to too high a dose toxicity, put it on the shelf, it's over. Super gonorrhea is almost untreatable. Pseudomonas and hospital acquired and ventilator associated pneumonia is a 50-50 chance of survival. We got to change the game and that's what we're doing at Texas. 

0:14:34 - David Williams
So it sounds like you know there's a couple of anecdotes that maybe paint the big start to paint the big picture, and we've been hearing about these things for a while. Are we at, are we hitting a crisis point? I mean, if we if I, you know come back next year, is it going to be going to have a bunch more examples as it starts to hit sort of like the mainstream? Yeah, I have, you know, cellulitis or something, and I'm just the antibiotics are just not going to work. How is it going to come upon us if we're not successful in dealing with it? 

0:15:01 - Greg Mario
Yeah, I think, if we use COVID, a virus, as an example. So COVID and viruses are like Santa Ana winds they rise up, burn and they go away. Bacteria are insidious they creep up and they keep creeping up and they keep creeping up. So in a year from now it might not be a whole lot different. It'll be worse. Yeah, brick by brick. 

But the projections have it that by 2050, if we don't make a game changing move here, tens of millions of people will die every year and make COVID look like a walk in the park. It's COVID times 100, perhaps 1,000. But it's sneaking up on us and it's been doing that for a while and you can see all the literature that shows the projections of death. We have to do something about it. We have some time, you know, and that's why we've been working on this for 12 years and we're getting close to the finish line and it's going to change the game and it's going to help us win, because we can't live without bacteria, the biome, we can't digest our food right, but we can't live with them. When we're immunocompromised, it goes from symbiotic to parasitic very quickly. It's a balance. The whole idea with bacteria. It's a balance. We live with them or we. You know, we can't live without them. So, to answer your question, within a year it's not going to be much different. Within five, yeah, very much within 10. 

0:16:38 - David Williams
Big time, that's the wave that's coming so so you say, been working on this for some time now. So what? What are you trying to do in this space? What's Taxis doing here? 

0:16:47 - Greg Mario
So, unlike a lot of historical antimicrobial development efforts, we're not really developing antibiotics, we're developing anti-resistance solutions. So there hasn't been a transformational change in the technology since the early 80s. Two things one, the beta-lactamase inhibitors and everyone has gotten amoxicillin for an ear infection when they were kids right, and your kids probably got them. And then you know, for 40 years it worked and stopped working. And then researchers at GSK determined that there was an enzyme that these bugs were producing called beta-lactamase, and the first beta-lactamase inhibitor was released in the 80s and that was clavulanic acid, not a household name, but when combined with amoxicillin, voila Augmentin was born. Same exact drug. That didn't work. But knock out a resistance mechanism and it works. 

So it's like you know someone comes to cut your lawn, trim your tree, it's going to grow back. They got to come back. And you have these incremental innovations over the last 40 years that are meaningful. The third, fourth, fifth generation fill in the blank monobactem, cephalosporin, tetracycline, et cetera. But it's not the root cause. We at Taxis, we're trying to rip it out from the root. I don't want the landscaper to come back. The problem is gone and that's what we're doing. That's what we're focused on. 

0:18:33 - David Williams
Now, you recently got a grant in this space and I want to ask you a little bit about that. The way you've described antibiotic resistance, it's definitely a public health threat, and so it's not shocking that you would have some organizations maybe both on the public side and private side that would be seeking to address that with some dollars. Who is providing grant funding on this topic? 

0:18:56 - Greg Mario
Well, so the primary sources of grant funding at least non-dilutive, it's coming from the National Institutes of Health, nih, and in this case we got a grant from the NIAID National Institutes of Allergy and Infectious Disease and they're very focused on certain disease areas and they have different ones that come and go and it's a great source of funding, but it's very competitive, very difficult. The private side is different. Private is about pure profit, you know, return on investment, which is fine. We're in a capitalist society and they expect that they're going to get equity or they're going to get, you know, get some value. And upside the public funding sources, all they care about is are you viable and you're not going to go out of business? And if so, we'll give you money because we believe in your science, technology and your team and it's been proven for taxes. 

That Carbex, which is a quasi-public-private fund. That Carbex, which is a quasi-public-private fund, a bunch of big government agencies German, us, british and also high net worth individuals like the Gates Foundation and others because they see the writing on the wall and this is a big problem. So they started a fund. We got funded for a very interesting combination therapy. That, I think, is a knockout and we hit all of our milestones, but they'd run out of money. So then we shifted gears, didn't wait for them and we went to the NIH. So we're actually getting the same project funded for a second time, just moving it toward the clinic, and after this NIH grant of 2.7 million, we'll have our first e-flux pump inhibitor in the clinic in the clinic. 

0:21:10 - David Williams
And so what are the requirements that you have to hit in order to you know? 

0:21:12 - Greg Mario
to fulfill the requirements under this grant. Well, it's basically a small business plan, right? So you know, in science there's a hypothesis. This is what we think. There's a plan. Here's how we're going to approach it. There's a project timeline, there's a budget. That's pretty much what it is. And if they think that, first of all, the objective is something that's meaningful to us, okay, next step. And then let's talk about your team and your people capabilities. Okay, next step. And then let's talk about your team and your people capabilities Okay, next step. And let's talk about how are you going to do it and how much time is it going to take and how many resources and how much money. 

So it really is like building a mini business plan. It's very rigorous, it takes a lot of time, a lot of effort and early in the days of this company, we went after a bunch of grants that I had a good feeling we wouldn't get because we didn't have everything. But it was a great way to organize the team of scientists. Ok, here's what we're doing. Here are the objectives. Let's get focused. You know, we're not academicians just looking for a publication. It's important to have a publication, publish or perish. But that's not the objective. The end game is get a drug on the market. So it's a great exercise, but, boy, it takes a long time, I got to tell you, and it's a very competitive space. So you have to have something that catches their attention, they believe is relevant, high in unmet need, and they believe in you, your science, your technology, your team, that you can get it done. They believe in us. Now We've been recognized. That's something that's a feather in our caps and I'm very proud of. 

0:22:59 - David Williams
I like the idea and you mentioned the term before non-dilutive funding. You don't have to give up a share of the company in order to get the grant. That's correct. What's it like in practice, you know, is it better than having an investment? Is it just different? 

0:23:17 - Greg Mario
Well, on the one hand, it's certainly better for our investors. Right, as a fiduciary, I'm trying to max out the return on their invested dollars and this doesn't take anything. It's like free money, but it's not really free. No, because you have new people who are going to be looking over your shoulder and you have to respond and report to them. But you know what, as long as you're executing on the plan that they approved, they're cool and the data drives the bus, we can't force it to work. I can't guarantee that we're going to win, but I can guarantee that we're going to figure it out and we're not going to have a false negative. Right, that's the critical. False positive you figure them out after a while. False negative is like missing the bus. 

0:24:08 - David Williams
Yeah. So you come across something that that could have worked, and you and you miss it. 

0:24:14 - Greg Mario
Yeah, that's the only thing that makes me a little afraid. 

0:24:17 - David Williams
Everything else I got under control, but that you know so you mentioned you've been at it for a dozen years or so. How has the company that's not that long Right? How has the company evolved since you started it? I mean, was the vision very much to be where you are today? 

0:24:37 - Greg Mario
No, totally different Life business. You know it's an iterative process, and especially in science. You know Aristotle had some theories. They were all wrong, right, but it builds on itself. 

So we started out heading in one direction and it just didn't look like it was working. And after about two years into it I was ready to wind the company up and I was really kind of down. You know, I had so much energy and I was so excited and my scientific founders were excited and the stuff we were working on just wasn't working. I was ready I had to kill it. And then, hallelujah, our chief scientific officer, dr Ajit Parhi, who's the engine of our science, and our team. He came up with this idea. He said I see something that's hitting the same target we're working on. That looks interesting. I have an idea and it just turns out it was a formulation play, a solubility play, and that's the drug that is now an oral anti-MERS drug candidate that's gone through the first step of phase one with healthy volunteers, no serious adverse events, no dose limiting toxicities, and we're pushing that through the clinic and it's a very important drug. 

Oral bioavailability is critical. Most of these drugs are based on plants and they're big, so they have to be IV Anyhow. So I was ready to shut it down. Keep your eyes open, stay on your toes. You know don't get wedded to anything, but you know don't get down. You know the data drives the bus and if the data is good, we push forward. I operate by the it as fast as I can to a critical milestone and if it's not working, cut it off, jettison, move on. And we've pivoted and moved and now we have a portfolio of drug candidates that are all novel and cutting edge technology that hit six of the CDC's top 10 deadliest bacterial pathogens. So we're going after a big net. 

0:27:04 - David Williams
It's a portfolio Sounds great. My final question for you, Greg, has to do with reading and if you have any opportunity to read any books and, if so, anything you'd recommend or recommend that we avoid. 

0:27:20 - Greg Mario
Well, I don't have as much time to read as I will when we're done saving the world, but I've always been into spy novels and sci-fi, so I just re-read Asimov's Foundation series, which I love. I mean, this is a guy in the 50s used to get on a train and they had phone booths on trains. This is a guy in the fifties used to get on a train and they had phone booths on trains and he would sit in a phone booth and he would spend the whole day. He'd go round trip, or maybe twice. Very strange man but incredible. 

Um, and some of my favorite authors Ken Follett uh, spy novels, key to Rebecca eye of the needle needle. His best work, though, was something in a totally different genre. He wrote pillars of the earth, which you might have seen on tv, and it's one of my favorite books I've ever read and I sent it to every person I knew back when it came out. Robert ludlam, the born series we see the movies right, but that guy had, he had a vocabulary like William Sapphire. It was brutal, and I had to read his books with a dictionary and a thesaurus next to me, but it taught me the English language. And, of course, stephen King. 

0:28:37 - David Williams
Enough said Sounds good. Well, that's it for yet another episode of the Health Biz podcast. I've been speaking today with Greg Mario, CEO of Taxis Pharmaceuticals. We've been talking about drugs to fight antibiotic-resistant infections. Greg, thanks so much for joining me today on the Health Biz podcast. You've been listening to the Health Biz podcast with me, David Williams, president of Health Business Group. I conduct in-depth interviews with leaders in healthcare, business and policy. If you like what you hear, go ahead and subscribe on your favorite service While you're at it. Go ahead and subscribe on your favorite service While you're at it, go ahead and subscribe on your second and third favorite services as well. There's more good stuff to come and you won't want to miss an episode. If your organization is seeking strategy consulting services in healthcare, check out our website, healthbusinessgroupcom.