Press play to listen, or check it out on your favorite platform:

About Dr. Maria Maccecchini

Dr. Maria Maccecchini has dedicated her 30-year career to the study of neurodegenerative diseases and their possible treatments. Her experience in biotechnology, the pharmaceutical industry, healthcare, and biomedical research has laid a strong foundation for addressing complex problems in life sciences focused on the development of breakthrough therapies.

Presently, she is founder and CEO of Annovis, her second biotechnology company, having sold the first one. Annovis is a clinical-stage specialty pharmaceutical company committed to developing therapeutics with novel approaches for the treatment of cognitive impairment, Alzheimer’s disease (AD), Parkinson’s disease (PD) and Down syndrome (DS).

Dr. Maccecchini has extensive experience as a public and private company board member, as an executive officer, and as a member of scientific advisory committees, and is skilled at investor and scientific communications. She speaks and write four languages – English, German, Italian and French.

Episode Highlights

How innovation works in pharma and why it matters to life sciences entrepreneurs
How success and wealth play out in life sciences and what it means to founders
The unexpected lessons from repeat entrepreneurship in life sciences
Why VC funding is challenging to raise in life sciences startups
How unexpected shocks from bad actors in the system can derail your startup, and how to tackle them
The nuts of bolts of getting FDA approval, and the factors that make it challenging
Why life sciences entrepreneurs decide to IPO
The challenges of being a public life sciences company CEO, and tips on handling the job
Personal lessons from a lifetime of curiosity and play that anyone can follow.

Links and resources

Annovis: The life sciences company that Dr. Maccecchini founded and runs
FDA: The U.S. Food and Drug Administration
Delaware Crossing Investor Group: An angel network that was one of the early investors in Annovis
Robinhood Ventures: A leading mid-Atlantic angel investment group
Ben Franklin Technology Partners: Leading technology-based economic development program based out of Pennsylvania.

Interview Transcript

Shubha K. Chakravarthy: Hello, Maria, we’re so happy to have you here today. Welcome to Invisible Ink.

Maria L. Maccecchini: Well, thank you so much for having me. I’m really happy to be here.

Shubha K. Chakravarthy: So we have a bunch of exciting things to talk about, but just to get started, can you just tell us a little bit about Annovis and what your company does?

Maria L. Maccecchini: Yes, so I know this company is kind of my teenager. In the meanwhile, I’ve been nursing it for 15 years from inception all the way to here, and they’re getting close. Interestingly enough, the analogy of teenager works really well because I think we have three years from graduating, so we are one study away to get FDA approval to be on the market for Alzheimer’s and for Parkinson’s disease.

Shubha K. Chakravarthy: That’s fantastic. Congratulations. And we’re cheering you on for that eventual graduation. So, clearly, life sciences is challenging, it’s got its own quirks.

I want to talk a little bit about how you found your way to a sustainable business model. So, first of all, you have a PhD. You come from an academic setting.

What triggered the move from academia? What made you decide, “Hey, I’m gonna pursue this on a commercial basis”?

Maria L. Maccecchini: Yeah, that is a very good question because when I studied, I was first going to be a professor. Okay. So I did two postdocs, a PhD and two postdocs, and then I said, I don’t think that’s really what I want to do, because when you do research – basic research, you find very novel things, but you don’t develop them.

They don’t become drugs. They remain on the research level. And then 20 years later, somebody else develops them and they may become a drug, but it’s 20 years later. And so I went to pharma and then I go, “Ah! This too big. It’s too many layers, It’s too slow”. So I went to a small pharma and I was really good.

I did really well for this guy and so I go, “ah, maybe I should do it for myself”. And that’s really how I started the company. And of course, I didn’t pick anything easy. I picked nerve cell death. I wanted to protect nerve cells from dying in stroke. And so I’m still at it.

Challenges and Vision in Life Sciences

Shubha K. Chakravarthy: So, clearly you have experimented with a bunch of different paths. So when you started this company, you already knew what it could become, right? So what was your vision? Did you have a concrete vision? Like, here’s where I want to be, here’s my end game playing out?

Maria L. Maccecchini: Yes and no. I thought we were doing Alzheimer’s disease. And I thought that I was protecting nerve cells from dying, which really is what I wanted to do in Alzheimer’s disease. What turned out as we did more and more research is that we were also protecting nerve cells from dying in other diseases in animals.

I can tell you we do it in stroke, in traumatic brain injury, in glaucoma, in Alzheimer’s, in Parkinson’s, and in fronto-temporal dementia. In humans, it’s hard to know whether your brain cells die because I would have to kill you and count them. That’s not very doable. But it’s interesting that the drug that we invented is expanding into neuro-degeneration, which is wonderful because it really helps a number of different diseases.

Shubha K. Chakravarthy: So, is it fair to say – I’m not a life sciences specialist, but what I’m hearing you say is you wanted to prevent the nerve cells from dying, but then you kind of moved upstream a little bit and said, before they die, they have to get sick. So why don’t we catch them and prevent the damage from happening so that they don’t die, as opposed to just preventing death at the end point. Is that accurate?

Maria L. Maccecchini: No, that is exactly right. The earlier you catch ’em, the less they die, because you’re right, you get a little sick, then you get more sick, then you’ll get more sick, and then you die. So yes, the earlier you catch them, the more you can recover them, and they do well.

Shubha K. Chakravarthy: So I want to expand on that a little bit. So you’ve been working in big pharma, then you move to small pharma and then you quit, and then you say, I’m going to do this on my own. And then you also talked about all this research. How does that timeline play out? Like, did you do all this research while you were in your startup? Or how did it all kind of come together?

Maria L. Maccecchini: Well, when you work for pharma, you are not allowed to do research outside of pharma. Whatever you think, whatever you believe – all your ideas belong to pharma. That is not unreasonable because we do that in my company. If you work for us, whatever you think, or your inventions belong to us, so that’s normal, which means I had to quit.

I had to quit my job and do it on my own because otherwise I would have infringed on my employment agreement.

Shubha K. Chakravarthy: Exactly, and I understand that you have to assign IP like the day you start working because you’re using their resources, their knowledge, all that good stuff. So you start, now you are on your own. At that point, were you clear that you wanted to prevent the death of nerve cells

Maria L. Maccecchini: I always wanted to prevent the death of nerve cells.

First Company and Lessons Learned

Shubha K. Chakravarthy: So starting out, let’s say day one, you’re off in your new office. You don’t have money yet? I don’t know. Like what are you thinking about?

Maria L. Maccecchini: Well, I, we jumped a little. Okay.

This is my second company, my first company that was the same. I quit and I wanted to protect nerve cells from dying in stroke, not in Alzheimer’s, in stroke. I wanted to protect nerve cells from dying – in stroke, not in Alzheimers. And so after nine years, that didn’t work. Needless to say, there’s still no drug that protects nerve cells from dying. But we sold the company to a genomics company, and so we made money and then I retired for eight years. Then I got bored and I started this company and I wanted to protect nerves from dying in Alzheimer’s disease. Now you said no money. The first time around I had $150,000. The second time around I had a bunch of millions, from my first company.

So it was a little easier, but a lot longer because – I spent the first 10 years of this company making a salary of $40,000 a year. I put in more than $3 million in cash into the company. So by the time we finally had some human data, I was pretty broke.

Shubha K. Chakravarthy: Wow. So it looks like we should have a whole other episode on the first company, but we’ll try to make it an omnibus conversation. So you had this earlier company for nine years that was a successful exit. What were the biggest challenges in your first go around that you found that you could better handle in your second, at bat?

Maria L. Maccecchini: Do you want to know the truth? It was the other way around. My first go around was a lot easier. The investors still believed in biotech and they still thought that if you have a few mice, they’re worth something. Now nobody believes anything. Too much has failed.

Mice are not considered a model for anything. Especially in Alzheimer’s, everything fails. Why would I not fail? So actually the second time around was a lot harder. A lot harder. I really didn’t think so.

Shubha K. Chakravarthy: So it was against, like, it, it surprised you, it sounds like, in terms of how hard it was going to be.

Maria L. Maccecchini: Yeah, I’m running into walls all the time. Like two weeks ago, the New York Times had an article on cheating in Alzheimer’s, and a guy who was in charge at the NIH had to retract over 50 patients. A guy who was the dean of Stanford had to retract papers. A company had to retract papers. They actually manufactured their Alzheimer data. The people that invented over 15 years ago that oligomers are toxic. The papers were found to be fake. So if all these great people, great positions, very famous names, if they all cheat, why wouldn’t I cheat?

Shubha K. Chakravarthy: Wow. So it feels like you were living in a more trusting, optimistic time the first time you built

Maria L. Maccecchini: Much more.

Shubha K. Chakravarthy: And then what happens?

Maria L. Maccecchini: Nobody believes a word.

Shubha K. Chakravarthy: So, we’re talking like 15 to 17 years between the time you started your first company and the time you started the second company. And by the time this rolls around, things have dramatically almost changed 180 degrees

Maria L. Maccecchini: We still have bubbles. Remember, people jump into AI, people jump into, yeah, mostly AI now. Okay.

Shubha K. Chakravarthy: Before it was crypto or Web3.

Maria L. Maccecchini: But, AI is good. Remember every time we have a bubble, it’s not that what is in the bubble is bad, it’s just that it gets hyped up and then it crashes. We still have bubbles, but Alzheimer’s is definitely not a bubble.

Shubha K. Chakravarthy: That I can agree with.

Navigating the Funding Landscape

Shubha K. Chakravarthy: So, you sell your company, there’s an eight year gap where you said you were retired and you still decided to take a leap into this other company. Now clearly you had some resources were you aware of, like how were you keeping track of what was happening in the landscape during this time that you were retired, and what triggered the move?

Maria L. Maccecchini: That’s a good question. It wasn’t easy to come back, to be honest, because as you just said, you kind of lose track. But the other thing is also how people perceive you. If you have not been around for six, seven years and all of a sudden you show up, they say, what are you doing here? And, we have a brain. We have, hopefully the brain still works. You learn and you move. I just at some point realized that I was getting really bored retiring then was just too early.

Shubha K. Chakravarthy: And so you basically came back to your first love and said, Hey, I’ve done something. But there’s still big problems here that need to be solved. You think you have a shot at solving it?

Maria L. Maccecchini: Yeah. And I didn’t succeed. Remember that I did not succeed in protecting their cells from dying. I succeeded at making money. That’s two different things.

Shubha K. Chakravarthy: It’s a very good point. So what was different? Was there anything different about your strategy or your approach that you learned from your first time around? How did that whole experience inform what you are going do with Annovis?

Maria L. Maccecchini: Well, number one, I learned that having a laboratory is very expensive and is not practical. We had a large lab in my first company. As I said, it’s very expensive. You need more than a few people because if you just have three chemists, it’s not enough. You need a team. So we didn’t. We are farming pretty much everything out. We have several offices here, a bunch of offices, but we don’t have labs. So number one, I’m a lot more virtual this time around than the other time around. Number two, I was wrong. I thought it was going to be easier. Instead, it’s harder.

Shubha K. Chakravarthy: And what would you say is unique about how you are approaching this versus maybe how the rest of the industry is approaching it? And secondly, how are you addressing this cheating aspect? This, the headwinds that are coming up where there’s more suspicion?

Maria L. Maccecchini: Well, the cheating aspect, I try to give people real good data and what is really disheartening is the FDA believes it and the street- Wall Street -doesn’t, which is totally bizarre anyhow, so you know about the cheating. We just have to let it blow through and show good data. There is really no other way. I don’t lie. Doesn’t make any sense.

So we just need good data, so we need to raise money and move forward in terms of how we are different. Yeah, that’s an interesting thing. So when a brain gets injured, a nerve cell gets injured, what happens is that it forms toxic proteins. They try to fight off the injury, but because there is really nothing there, the brain is intact. It just gets hit, but there are no bacteria or something. All these toxic proteins accumulate and they become toxic to us. They turn against our own brain. There are several toxic proteins.

Now, most people have heard of plaque plaques in the brain. That’s Alzheimer’s. It’s part of Alzheimer’s, it’s not Alzheimer’s. Some people have heard of tangles that’s also part of Alzheimer’s, and again, it’s not Alzheimer’s. And then some people have heard of Lewy bodies. Lewy bodies are part of Parkinson’s. We are separating. We’re saying, this is here and this is there.

It’s not true. Everything is everywhere. So we have plaques, we have tangles, we have Lewy bodies in an Alzheimer’s brain, and so you have to remove ’em all. What pharma has been doing is being very specific for plaques or tangles, or Lewy bodies, and that gives a very small improvement. Not a big improvement and what we are doing and the preliminary data proves that – by removing all three, we actually also remove TDP 43 aggregates. By removing all four, we have much better data.

Shubha K. Chakravarthy: So in other words, you are kind of hitting at a much more root cause remedy.

Maria L. Maccecchini: Yes.

Shubha K. Chakravarthy: So the delta of improvement is much more than just maybe a downstream affecting a downstream effect like a plaque, is that a fair statement?

Maria L. Maccecchini: Exactly, because when the brain gets injured, it makes all these proteins and we take them away – at the beginning, when it gets injured. We don’t wait until they form these aggregates.

FDA Approval and Commercialization

Shubha K. Chakravarthy: So you made a very interesting remark earlier, which is, FDA believes it and Wall Street doesn’t believe the data that you come up with, which kind of suggests to me this tension between commercial and the scientific, which you have to deal with head on. Just given what you do, how do you experience that and what’s your approach to tackling that conflict?

Maria L. Maccecchini: I’m not sure it’s a conflict except that it’s a cognitive dissonance in some ways because ideally you want to develop a drug that works and give it to free for the whole world, right? Now, realistically, I need millions of dollars, hundreds of millions of dollars to make the drug, to get the drug approved, to get it through the FDA, to test it, and that costs a million dollars.

So the people that give you the money don’t do it so you give the drug away for free. They do it so they make a return on investment. And so I think these are two totally different things. One is you want to develop a drug because you believe in the mechanism. You believe it protects nerve cells from dying.

That’s why I want to develop a drug. I want the nerve cells to be alive because then people don’t get demented, they don’t lose their function. That is my goal. But realistically, the people that give me money want money. Pharma is not going to make it for free if they sell it. That’s why usually the scientist is not the one that sells it. The scientist invents it and then somebody else does the sale. Like, they’re two different modalities.

Shubha K. Chakravarthy: But you bridge that, right?

Maria L. Maccecchini: I’m not selling anything. I don’t have a drug yet. We are still developing it. Yes. However, the sales I have to do is sell the company and the drug – to get the money to do the studies. Yeah. That’s the sales I have to do.

Shubha K. Chakravarthy: So that actually brings up an interesting question, and you mentioned this I think briefly earlier. In what way does your life sciences company differ from, does it differ from a typical other company that is in life sciences and is actually trying to sell drugs? Is there a fundamental difference in the business model and approach?

Maria L. Maccecchini: Not really. Basically what we all do, independent of what we do, we go ask people, give money so I can do the next step, because it’s a long process. Just today we had a news release that said we enrolled two first people into a 750 patient 18 month study. That takes forever. It costs a ton. But today we enrolled the first two patients, so we are very happy about that. For that I need money. So what is different about me and a whole bunch of other companies is more the length. I have survived for 15 years and we are close to commercialization. We are three years from commercialization.

Usually, companies if you try to come, they’re much earlier on. And the trouble is, and that’s why the street is right about not believing a word. The trouble is that 90 to 95% of us die. They just die.

Shubha K. Chakravarthy: The companies, you mean the startups that are trying to commercialize the drug and take it through the approval process so it just ups the risk, which means that it’s ups the return that they’re expecting from them?

Maria L. Maccecchini: Yeah. Well, I think it lowers the risk because we have done a thousand patients already. We have a ton of data. But the FDA wants, one and a half thousand patients total for Alzheimer’s and one and a half for Parkinson’s. So we are still 3,000 patients away from – 2,000 patients away from both diseases.

The problem with smallish, our studies are not that small, but with smallish numbers, is that they could be skewed. You could see statistical significance where there is none because of chance.

Shubha K. Chakravarthy: So, you’re laying out a torturous path. It’s an arduous path to getting to commercialization, but it feels fairly well known. You have to go through these toll gates. there are risks at every point where you might have to go back and redo things. Has any of that changed or did any of that evolve or turn out to be different than what you expected when you started? For example, did you have to enroll more patients than you expected? What were some of those?

Maria L. Maccecchini: Well, the FDA wants one and a half thousand patients. You can stand on your head and wiggle your toes. The only way you don’t have to do that is if it is an orphan indication. That’s why a lot of people do orphan indications, but in large indications, you just need a lot of people.

Shubha K. Chakravarthy: And what is the difference between the two?

Maria L. Maccecchini: Orphan indications, they’re less than 250,000 people in the United States. So if it’s a rare disease, but you know, 250,000 people is not a lot of people. And very often small companies go for indications that have 40, 50, 60 patients. So they are easy in some ways they’re not easy because you have to get every patient in the world

Shubha K. Chakravarthy: So, so it sounds to me, and correct me if I’m wrong, it sounds to me like you knew what the path was and you knew that inherently the outcomes were very widely distributed. The FDA could come up and say whatever, and you really couldn’t control it. You couldn’t really predict it too much, and you are bound by whatever they say.

Maria L. Maccecchini: I think the FDA can say whatever. The FDA is actually quite consistent. The FDA wants you to do a lot of people. Because of safety. Remember, biops or even talcum powder, for heaven’s sake, if not millions of people hadn’t used it, people would have never figured out that it could cause cancer, right? If just three people use it, it would not cause cancer.

So the FDA has always said you need to do a lot of patients. That has never changed. The FDA has always said you need a study that shows efficacy. That has not changed. I don’t, I didn’t think it was going to be that hard. That is the difference. It’s maybe my underestimation of reality.

Shubha K. Chakravarthy: So the hard part was finding the patients, or the hard part was?

Maria L. Maccecchini: No, the hard part is finding the money.

Shubha K. Chakravarthy: finding the money.

Maria L. Maccecchini: Finding the patients is not hard. They’re so thankful because we give them an option that is simple. We give them a one a day pill, that’s it. Whereas other indications, they have to come in for infusions. They have to come in for a lot of machines, like MRIs, like CAT scans, and we just say, come in once, one a day, a pill. Then you go home and you come back when you have no pills left.

Shubha K. Chakravarthy: So we’ve talked a lot about how important funding is and the huge numbers involved here. Can you just say high level, walk me through like what was your expectation of how much you would need at different points in the journey, and how did that actually relate to what turned out to be the real need? Was there a difference there?

Maria L. Maccecchini: I think I, I underestimated the cost. Because I thought you could do it with 20 to $30,000 a person, when in fact it costs a hundred thousand dollars a person. So a 750 patients study costs $75 million.

Shubha K. Chakravarthy: That’s a lot.

Maria L. Maccecchini: The way that you pay the doctor, you pay the nurse, you pay the statistician, you pay the medical monitor, you pay – whoever you pay, the nurse that weighs you, you pay the person that collects your urine. You pay the person that asks you all the questions and, I calculated it. It takes one person in staff to treat two people. So for total, for a 750 patient study, it takes over 300 people to service that study. And I never knew how many regulations there were, how many people it takes, because also the responsibilities are very slim. One person does this, one person does this one person. You don’t have a person that just does everything.

Shubha K. Chakravarthy: Is that different from the last time around that you did this?

Maria L. Maccecchini: I did not progress that far. I started much earlier. I only went to phase one. Now we are in phase three. And phase three are very complicated studies even when they’re simple.

Shubha K. Chakravarthy: So it is more a question of you’re now progressing much further than you went in your last startup, and you’re discovering a lot of these facts for the first time. So now clearly the funding need has multiplied, right? Compared to what you thought it was going to be. So what do you think you were going to do?

What was your fundraising strategy before you kind of discovered all these new realities? And then how did you evolve your strategy over time?

Maria L. Maccecchini: I just take one step in front of the other. I mean, look, we just closed on financing and we start the study the next day. What do you want me to do? It was really kind of, sure – we could, if we had money in the bank, but you know, the money in the bank was not enough for the study. So, no, you just do what you have to do.

Shubha K. Chakravarthy: And from that, from a perspective of life science founders, that means just going to the traditional VCs and other funders.

Maria L. Maccecchini: No, VCs don’t pay me at all. See, that was when you are private, you have VCs. We need too much money because, Delaware Crossing or Robinhood, the small funds. Okay. They don’t have enough money to do a $50 million study. So at that point I had to go public. We went public and now I can raise money on the Street, but that’s why the Street is much less kind. They are really brutal. And after they read this article in the New York Times, they were really brutal.

Fundraising Journey and Going Public

Shubha K. Chakravarthy: So, okay, so now I know you raised angel funding early on. Can you walk us through what your fundraising journey was and how you made the decisions at each point?

Maria L. Maccecchini: Yeah, I think my very first money came from Ben Franklin in Philadelphia. And then we had a little from Delaware Crossing, we had some from Robin Hood, we had some from some others. And then I put in a bunch of money and then we started getting slightly bigger investors, but still individuals. And then at some point I realized that in order to do human studies, not animal studies, I needed a lot more money.

And so six years ago we decided to go public and we did.

Shubha K. Chakravarthy: What was that process like? What kind of preparation did you have to do personally as yourself and what kind of changes had to go, through in the company for you to be kind of IPO ready? What was that process like?

Maria L. Maccecchini: If I had known how much it took, maybe I wouldn’t have done it. Because my board, when I said we are going public because I can’t raise enough money as private, they told me, you are a PhD. You can’t go public. And I go, okay, fine. And so we went public, but that was my board. Okay. So sometimes not knowing what you get yourself into is good.

Because you know everybody’s going to tell you, turn right, turn left, jump up, jump down, jump sideways, jump to whatever. The most important thing was to find a good chief financial officer with public knowledge because I could have never – never, in my wildest dreams done all the financial paperwork that he did.

That was the most important thing. And then you need the lawyers. You need the bankers, you need the auditors. You need more lawyers. You need more auditors, you need more bankers, you need more consultants. It’s not per se, difficult. You can handle everything. It’s just a lot of stuff you don’t think about, dotting every last i and crossing every last t for the last three years because they had to go back and audit all the financials of the last three years , digging out all the data, all your correspondence with the FDA, because they want to make sure that what you say your correspondence was.

So it was just a lot of work. And yeah, I think the financial is the most important.

Shubha K. Chakravarthy: How long did that whole process, from the day you decided that you’re going to go public?

Maria L. Maccecchini: About a year, maybe a little less, I would say 10 months.

Shubha K. Chakravarthy: And was that pretty much what you expected in terms of this is how much it would take?

Maria L. Maccecchini: No, I thought it was gonna take three months (laughs).

Challenges of Being a Public Company

Shubha K. Chakravarthy: What was the biggest learning from the whole IPO experience for you?

Maria L. Maccecchini: Well, it’s really what I’m still kind of trying to learn.

Now, as a public company, we have to file with the SEC every three months. We have to file a ton of paper and I go, but we just filed and not much changed. Well, forget it. You still have to file it. It’s a lot paperwork. It’s just that, they have been trying to keep people from cheating, right? And so they keep dumping more regulations on the people that don’t cheat because the ones that cheat, they figure out how to get around it anyway,

Shubha K. Chakravarthy: So it just increases the cost of compliance to everybody else

Maria L. Maccecchini: The cost of compliance is ridiculous if you ask me.

Shubha K. Chakravarthy: So there’s the administrative burden, which is you have to hire people and they have got to go through all these reams of paperwork. What kind of a demand does it place on you as a CEO in terms of being public versus being private? How has that changed your life?

Maria L. Maccecchini: I have to read it all, but because I have to sign it, but that’s not the burden. The burden really is that I’ve become a public company and people think they can criticize me for everything. I give out data and some person who has no clue says I don’t believe it.

Shubha K. Chakravarthy: So, and I’m trying to understand this because you’re one of the few CEOs we have here who has gone public, so I’m going to make use of it. So, there’s a piece around, you’re answerable to investors. You have your report outs, you have your board clearly, and you’re answerable to them. So there’s that level of scrutiny and that level of accountability, for transparency. I get that.

But, all this data is public. So you’ve kind of exposed yourself or your data to other kinds of criticisms, other kinds of scrutiny, which, when you say people feel like they criticize you, like what part of the people are you talking about? Are you talking about like other medical experts?

Maria L. Maccecchini: No. The medical experts don’t say anything. It’s the Street. It’s the people that buy 10 shares. They compare me to another company and says this, and this company said that and that. Then why? How could you possibly do this? Some people have said the drug is too good to be true. It has to be snake oil. It’s tough.

Future Plans and Trials

Shubha K. Chakravarthy: So you mentioned that you were three, just a short three years away from graduation and completing the successful trial. We’re definitely behind you. What is, what’s the next step then after that? What happens once you complete that?

Maria L. Maccecchini: The next step is really being done with this trial. The study we just started today, actually started it yesterday, but we had the news release. Today is an 18 month study that we look at the data at six months. At six months, it’ll give us short term efficacy. Because what we saw in our small study, smallish study is that our drug works beautifully short term.

So people ask me, what does it work long-term? Well, I don’t know. In mice does, but in humans, I only tested it short term, right? So the first six months confirmed the short term efficacy. Then it continues for 12 months. And the 18 month study will then tell me if it works long term. And so this is, as I said, the 750 patient study 18 months, which takes three years.

And after that we will know short term and long term. If it works short and long term. That’s amazing because right now there is no drug that does that, not.

Shubha K. Chakravarthy: And then you become a very attractive acquisition candidate.

Maria L. Maccecchini: Yeah. But yeah. But then I will be a very attractive acquisition target. Yes.

Shubha K. Chakravarthy: And hopefully become very rich, which we’re again rooting for.

Maria L. Maccecchini: That’s not what I’m shooting for. And then I want to do the same for Parkinson’s.

Shubha K. Chakravarthy: Yes. So you can go on and do, conquer more diseases and save more nerve cells, whatever floats your boat!

Maria L. Maccecchini: Yes. I tell you I want to do Parkinson’s. I want to do Lewy body dementia, and I may want to do ALS and MS.

Shubha K. Chakravarthy: That’s fantastic. I had a relative who passed away from ALS, so I’m definitely rooting for you.

Fundraising Journey and Personal Growth

Shubha K. Chakravarthy: So looking just to round out this whole fundraising journey. It’s been a long journey. You had your first startup, now you have this startup. What are some of the big takeaways in terms of funding journey for you personally?

How did you transform yourself from a scientist who speaks scientific language to a business person who’s a business person who speaks the financial and commercial language?

Maria L. Maccecchini: Maybe I’m not, I’m still not that good at it. I really try to simplify things and I’m told I’m good at that. However, where I’m really not stellar is in selling. Because I see other people that have less than we do. They’re better at getting money than we do, and I’m not sure why exactly, but there are definitely people that are better at getting money than I am.

Now that doesn’t mean I don’t get it. I got it and our accountant has been with me for 15 years. In the meantime, she knows that I’ve always gotten the money. She was always paid no matter how bad things were. At some point the money just comes, but I really think that some people are better at getting money than I am, and it’s credibility. It’s maybe being able to hype better.

It’s not explaining better. I’ve gotten very good at explaining, but somehow I’m also told I may be too honest. I will tell you it worked here, but it didn’t work there. In fact, I just told you it works beautifully short term, but I don’t know what it does long term. I would have to say it works, but then I would feel that I’m dishonest.

Shubha K. Chakravarthy: And to what extent has your, having this really experienced CFO helped you make that sale and translate any of this stuff to the Street that maybe you didn’t feel, as comfortable doing or wanted to do?

Maria L. Maccecchini: Still honest. I still say it works here. It doesn’t work there. So I don’t think I can change and see – the way I see it is in the end. Okay, I may have more problems raising money now. Okay. But in the end, what counts is will the FDA approve the drug or not? So if I tell you it works and then it turns out it doesn’t work at 18 months, well, it didn’t work right?

Shubha K. Chakravarthy: So it’s a question of what’s your timeframe and you’re shooting for a long enough timeframe where your words are going to get proven out and, they kind of go hand in hand versus, here’s what I’m telling you, and therefore I can get a higher price for whatever that means. Awesome.

Personal Background and Entrepreneurial Journey

Shubha K. Chakravarthy: So now I want to just talk briefly about your personal journey.

We’ve talked a little bit about you having to make multiple transitions. I know you’ve also had to move countries, so what are the biggest transitions that you had to make personally, going from your initial academic focus to where you are today, and how did you make those transitions successfully?

Maria L. Maccecchini: I think it came from me wanting to do something all, not by myself. I have a great team. I can’t develop a drug, but having my own project and taking it all the way to fruition, and that’s really what I’m doing. It’s going to take me 18 years, God forbid, but it’s starting with a drug, doing all the animals, doing all the humans, getting it through the FDA, and then actually getting it on the market.

I think I always wanted to do that. I always wanted to take something from the beginning to the end, and it just took, it took me longer than other people. You look at the people that make money in AI or in chips or whatever, they’re all much younger. But yes, it took me, whatever it took me.

Shubha K. Chakravarthy: It sounds to me like you, what really kept you going was this immense clarity about, I want to take it from point A to point B. I know it’s a challenging process. I know it’s a long process, but whatever curve balls get thrown at me, I’m going to just handle them in service of this North Star. And that’s it

Maria L. Maccecchini: Yes, absolutely. The second company, I was very determined to take it to the end. The first company – I wanted to protect nerve cells from dying in stroke, but I didn’t have a very strong feeling about how, where to go. And then it didn’t work and it didn’t work. So that made it kind of easier to stop.

But in this case, I really said this is my second chance of protecting nerve cells from dying, and I want to do it.

Shubha K. Chakravarthy: That makes sense. And to what extent has your personal background shaped your entrepreneurial journey? How has it shaped what you’ve done?

Maria L. Maccecchini: I grew up in a conservative family where my mom thought that the boy was gonna study and the girl was gonna get married, and mom had two miscarriages and two boys. They were both dead. so I was kind of the wrong sex, okay? Because she wanted this boy to, to be grandiose, and she was gonna shine in his limelight.

And so I somehow took over just very different from the way she thought. I was very good at math and I was the ultimate nerd. I was the nerd at school, was the best person at school. I always had A’s and my mom kept telling me that men don’t like intelligent women. I was never going to find a husband. I said, I don’t care.

So I in some ways took over what her son was going to be, but differently. I didn’t want to be a lawyer. I didn’t want to be a doctor. I wanted to be a scientist. That’s not shiny, that’s grubby. When I was 21 or so, I decided to grow cockroaches and termites. Okay. I took home big glasses, jars full of termites and stuck them in my room.

She freaked out. What could be more grubby than that now? They didn’t escape. They were very well contained in this glass jar and there was Vaseline around and I would feed them and she freaked out, so she never came into my room. So I, in some ways, I took over what she wanted. She wanted a very successful son, but I took over in the field, which she didn’t understand,

Shubha K. Chakravarthy: Was she ever in your way?

Maria L. Maccecchini: Oh, all the time she always told me to stop studying and find a husband. That’s why I came to the United States. It was much easier.

Shubha K. Chakravarthy: So you essentially ignored it. You decided to craft, but how did you pick up this message that’s what she wanted from a son?

Maria L. Maccecchini: She told me all the time. She kept saying if I had a son, he would be a lawyer or a doctor.

Shubha K. Chakravarthy: How did that make you feel?

Maria L. Maccecchini: So I didn’t want to be a lawyer or a doctor, but I figured it out.

Shubha K. Chakravarthy: Did it ever upset you?

Maria L. Maccecchini: All the time.

Shubha K. Chakravarthy: And you just, you decided to don’t get mad, get better.

Maria L. Maccecchini: Oh no, I got mad. We fought all the time. My mom and I fought a lot. A lot.

Shubha K. Chakravarthy: But a great outcome came up and I love it.

Maria L. Maccecchini: No, but see, I had a dad who was a lovely person. My dad supported me with the termites, with the cockroaches.

Shubha K. Chakravarthy: I love it. I absolutely love it. I think it’s the best story we’ve heard so far on this podcast.

One other thing you mentioned is, you know how important it’s to be a contrarian. I’ve heard you say that in the past. Can you talk a little bit about, how that has played into your journey and into your life, especially, with this, entrepreneurial journey?

Maria L. Maccecchini: Well look, if I wanted to have an instant success Alzheimer company, okay, which would have never developed the drug, but had a pharma deal, I would’ve done Alzheimer antibodies because all the companies, all the small companies got funded by pharma to do Alzheimer antibodies.

Now they don’t work. That’s a minor detail. But it’s what pharma was, right?

And I’ve always seen, I think it’s because I’m very curious. I just like different things, cockroaches, whatever. contrarian, I’m not sure. Maybe it’s, contrarian is the wrong word. It’s just that when people all believe in something, I go dig.

I say, “why does everybody believe in that?” And then I form my own opinion.

So it’s intellectual curiosity yes, it shows curiosity more than contrarian But then I don’t mind saying, no, I don’t believe it. I believe something else.

Shubha K. Chakravarthy: But what drives you, it feels like is not the drive to be a contrarian, but it’s the drive to know the real answer regardless of where that may land?

Maria L. Maccecchini: Yes, because I just looked up high fructose corn syrup. Okay, it’s sugar.

It’s sugar! What are we talking about!?

Shubha K. Chakravarthy: Well, that, that’s always known, that it’s sugar.

Maria L. Maccecchini: Yeah, but we say it’s so unhealthy. You know what the difference is between high fructose corn syrup and sugar?

Shubha K. Chakravarthy: I don’t.

Maria L. Maccecchini: I didn’t either until I, I don’t know why I looked it up. It’s somebody said that syrup was healthy and I don’t look it. Sugar is two molecules. This is sugar, right? Fructose, glucose. Goes into the stomach and in the stomach enzymatically split, and you have the two molecules separate in the stomach, but in the mouth it’s two molecules. Okay, well, high fructose corn syrup is two molecules. You stick ’em into a solution where they get split and then you ingest them. In the stomach, they’re identical. You know why they do that? Because it tastes sweeter.

Shubha K. Chakravarthy: So there’s no difference?

Maria L. Maccecchini: Before it goes into the stomach, if you split it in the mouth, which the mouth cannot do by itself, it tastes sweeter. That’s why they split it. But in the stomach it’s exactly the same.

I am not diabetic or anything. So stuff like that doesn’t really attack. So I think I looked at it because somebody was talking to a bit how healthy a cough syrup is. And in fact, a cough syrup is very unhealthy. It’s very unhealthy, it ruins your liver, and you know why

Shubha K. Chakravarthy: I don’t.

Maria L. Maccecchini: told you sugar is two molecules, one fructose, one glucose.

But it’s half and half. Syrup is 80% one and 20% the other, and the 80% of that attacks liver.

Shubha K. Chakravarthy: Oh, so there’s more of the stuff that attacks deliver than the other stuff. I learned something else today.

Maria L. Maccecchini: That is healthy. The other is unhealthy, and nobody knows why.

Don’t eat a cough syrup.

Shubha K. Chakravarthy: So then coming back, you painted a really fascinating picture of how both your personal upbringing and your own mental makeup helped draw your path.

Is there anything you’d say to your younger self today that you would do differently or that you know now that you didn’t know before you started all these, doing all these things?

Maria L. Maccecchini: Yes, I will tell myself I was pretty. Because, no, honestly, because of the fact that my mom thought I needed to be beautiful to attract this wonderful guy and get married. I walked like this. I wore an apron all the way until I was 17. I was the ultimate nerd. You can’t be more nerdy than that, and I thought it was ugly.

Instead, I look at my pictures, I was pretty.

Shubha K. Chakravarthy: You are for sure.

Maria L. Maccecchini: So, it’s just, it just took me forever to come out of this because I knew I was intelligent. I knew I was going to make it with my brain, but I did not think I was attractive. I did not think I could talk. Well, talk physics, okay, but not talk. Do you know what I’m saying?

And I would tell myself going back, you were a hell of a lot better than you felt.

Shubha K. Chakravarthy: How would that have changed your life if you had done that?

Maria L. Maccecchini: Would I’ve been more secure, maybe I would have worked less.

Shubha K. Chakravarthy: And maybe we won’t be here today, so who knows?

Maria L. Maccecchini: Exactly. Exactly.

Advice for Women in STEM

Shubha K. Chakravarthy: So, today you talked about some of the challenges already, right? In terms of the field being harder to break into with all of these challenges coming up. There are other issues as well in the current environment that may be not as friendly to women in STEM and life sciences. What do you think will help a woman founder in STEM and life sciences be more successful in the face of all of these challenges?

Maria L. Maccecchini: Now, especially where we have a new administration and we are cutting back on helping minorities and women. I’m not sure we are a minority, but anyhow. It’s really hard because I can slice it any way I want and it’s not helping. Let me explain what I’m saying. If you help me, because I’m a woman, I may not be that good.

I may be that good, but I may not be that good. And if I’m not that good, then you help me and you shoot yourself in the foot and I shoot myself in the foot because in the end, I’m going to fail. If you don’t help me because I’m a woman, I may not make it even though I’m really very good.

So the question is, what’s the right way to empower, promote, and help minorities? Because just saying we need 10% of this and 20% of that is not helping. Then you hire people and they fall through. Then you say, oh, they’re all stupid. No, they’re not all stupid. You hired the person that they don’t quite fit the job.

And that is a really tough question. And I don’t have a good answer. I really don’t. Because no matter how you do it, you would want to help a little bit, but not too much. And you would, you don’t have a crystal ball when you help people. You may help somebody who is clueless.

If you let them develop themselves on their own, then at the end, whether they were clueless or not. But you may have lost a few on in, in the way because they got no help. So, I don’t know.

Shubha K. Chakravarthy: It’s a challenge between false positives and false negatives.

Maria L. Maccecchini: Yeah.

Shubha K. Chakravarthy: So you talked about the other side, which is helping women founders. I’m wondering if you have any thoughts on the flip side, which is you being a woman founder. Is there anything you do differently in today’s environment or that you would advise people who are starting out companies in life sciences or in stem?

Maria L. Maccecchini: Well, first of all, I will tell them do not ever base anything on being a woman or a man. It doesn’t matter being gray or blue or yellow. It does matter. I’m not saying it doesn’t matter, but if you put your emphasis on that, you already single yourself out as different, so that doesn’t help. The other thing I would say the younger generation is more self secure.

I appreciate that. I see a lot of girls that have more self-confidence. Even if they got it from sports, it doesn’t matter. I couldn’t even do sports. I could only read books. So it doesn’t matter where they get it from, but it really helps to be more self-confident to put yourself out there.

I would also say one of the things that my generation had a harder time with is failing is okay and now today failing is okay. In fact, you say, it’s my experience. The other thing is we are a rich society. I know we’d say about this, that, and the other, but we are a rich society. You can afford to fail.

Even if the government changes, there’s always going to be money out there for startups.

Shubha K. Chakravarthy: So what I think I’m hearing you say, and correct me if I’m wrong, is, you focus on the substance of what you’re trying to do. You get yourself confidence from whatever source works best for you, whether it’s sports or whatever the else the case may be. But stand strong in your own competence, ensuring that you’ve earned that competence, and then be prepared to fail.

Because in this society, chances are you’re still going to survive and live another day to fight another fight.

Maria L. Maccecchini: Yeah, that is a very nice way of putting, be prepared to fail and don’t take it personally. And of course you’re going to take it personally, but move on.

Maintaining Curiosity and Youthfulness

Shubha K. Chakravarthy: Awesome. So, you gave us a lot of insight and amazing amount of, rich observations, from our life well lived. Is there anything I should have asked or anything else you want to add that we didn’t talk about?

Maria L. Maccecchini: The interesting thing is that in a lot of ways, and we never really, we talked a little bit about curiosity. I’m still a kid,I went, to Portugal with my brother and his wife and his little girl. He has a young kid, and we went on a trampoline and here I am. Okay. Seventy years old. I jumped, I did somersaults on the trampoline.

I did flips backward and forward with the 10-year-old kid. You think anybody else did then?

Shubha K. Chakravarthy: I can’t see myself doing it.

Maria L. Maccecchini: It was fun. Who cares? Yes. You look like an idiot. So what? To be a kid. that’s the most important thing.

Shubha K. Chakravarthy: Awesome. Fantastic. This has been an amazing conversation, Maria. I really appreciate it. Thanks very much for taking the time. I’m sure you’ll inspire a whole bunch of other women. Thank you so

Maria L. Maccecchini: Well, thank you so much, Shubha. It really was fun talking to you.