Advancing New Hope for Fibrotic Disease featuring Gian Luca Araldi

How does finding hidden temples inside the body result in a cure for IPF? Listen today.

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Welcome to The Connect Current, the flow of innovation in San I'm your host, James Zanewicz, and this episode is being recorded at Kiln in Rancho Bernardo. When you're looking for coworking space, look no further than Kiln. Today, I'm joined by Gianluca Araldi, founder and CEO of Avanti Biosciences and one of Connect's 2026 Cool Companies. Avanti Biosciences is a San Diego-based biopharmaceutical company developing novel small molecule therapies for serious unmet medical needs. including idiopathic pulmonary fibrosis and other fibrotic diseases. The company's lead program, ABI-171, is being advanced as an oral precision kinase inhibitor designed to address disease biology in a way that could potentially go beyond slowing decline. Antea has built a strong preclinical package, received FDA orphan drug designation, completed FDA pre-IND review, and is preparing for its next stage of clinical development, When do you sleep?

That's a good question. Not that much, actually, like my wife would say.

And aren't you proud of me with my chemistry degree, able to pronounce things? I know.

That's crazy.

Probably most podcast hosts are like, what's this word? I'm like, I actually knew. But anyway, that makes this such a great conversation for the podcast because you sit at the intersection of deep science, drug development, translational medicine, non-dilutive funding, and the long road from patient discovery to patient impact that we're all trying to shorten. And most importantly, as a 20 2026 Connect Cool Company. You're also part of that next wave of San Diego life science companies working to turn that technical progress into meaningful clinical opportunity. And I'm so glad to have you on the show.

Well, thank you very much for the introduction, James. Super introduction. Thank you so much.

Excellent.

Well, let's dive straight in, Gianluca. For listeners meeting you for the first time and hearing about Avanti for the first time, what is the company building? What problem are you solving? And why does that problem matter so much right now?

Well, Avanti Biosciences is developing a new small molecule for the treatment of fibrotic disorders. We are mainly focused on lung right now, but we also have very good data for another very much unmet need, which is liver fibrosis. We started our long journey about 9 years ago, and serendipity really played a big role in where we are right now. Think about it. We started 9 years ago working in collaboration with Professor Bill Mobley at UCSD, working on Down syndrome and Alzheimer's disease. And after 9 years, here we are talking about one of the most promising drugs for idiopathic pulmonary fibrosis. And we are so glad that we will be able to help patients. And I don't think people are familiar with idiopathic pulmonary fibrosis, which—

Yes.

After all, it's an orphan indication, so probably less than 200,000 patients are in the United States. But it's a terrible disease, probably worse than cancer. If you have IPF, it's like after 2, 5 years, you will die of a terrible death.

Yeah.

Think about it. You cannot breathe. And actually, one of our collaborators, her mother suffered from IPF. And we just spoke with her to better understand the patient. And she said, it's like, for my mom, it's like breathing glass every day. So it's a terrible disease and there is really no cure. So that's why we are very motivated and we're very hopeful to find a cure for this terrible disease.

Yeah. And as you're on the path to that cure, you bring a long background across pharmaceutical development, medicinal chemistry, manufacturing, and project leadership. So What did you see in fibrotic disease in that area that made you believe Avanti had an opportunity to approach that problem so differently than had been done before?

I think in many journeys, serendipity plays an incredible role. Think about it. Like I said before, we didn't start with fibrosis. I'm not a pulmonologist. I'm more like a generalist. I'm a medicinal chemist. You give me a project, I work on it very much. Therapy agnostic. But what probably set myself and my company apart from many other companies is that we are very much determined to find a therapy, whatever that is. So in our journey, we were developing drugs for Alzheimer's and we found a drug that was a good drug. We thought that has drug-like characteristics. But it was not exceptionally active for Alzheimer's. So we said, so what are we going to do? We have a molecule. Now we need to find a use for this one. And we look around, we look at what the class does and which therapy the same class of molecule is active. We found that actually IPF is actually a very interesting indication and we dive into that. So what set us apart as a small company, and I can speak for all the small companies that are in San Diego, Versus the big pharma is, and I have a lot of experience also working in a big pharma. So in a big pharma, if you have a molecule, a project, if it doesn't work, that's it. You stop and you move on. We as a small company, instead, we are hardheaded with much creativity. And if we have something, we need to put it at use. And that's what we did.

Mm-hmm.

So we start testing the drug in different animal models. We found that the molecule actually is very, very potent in IPF. And so we dived in and we are now Very close to clinical trials.

Well, and your lead program is being developed as an oral precision kinase inhibitor for idiopathic pulmonary fibrosis or IPF and the related fibrotic conditions we talked about. But what should our listeners understand about what makes this approach different from current treatments?

Yeah. So right now the current treatments are really not good. We have 3 approved drugs. that they're just slowing down the disease. In the words of the mother of a patient, she said, I gave this drug to my mother. My mother is worsening. And we don't know if it is worsening because the disease is worsening or because the drug makes her worsen because of all the side effects. So that tells you really we are not close to find a perfect cure for these patients. These patients, they need to have a new cure that actually stops and reverse the disease. Right now, the therapies that are available, they just slow down the disease, but the inevitable end is right there. You might make— it's like a cancer therapy. Usually right now, you don't cure cancer. You just increase the lifespan of the cancer patient. The same here is YPF patient.

So you started to dive into this a little bit, but for our non-scientific audience who's wanting to learn more about this, when you're talking about the difference between slowing disease progression or addressing biology in a way that could reverse the disease itself. How do you explain that difference and what the impact is from that?

Right. I mean, until now, the current therapies, they were born from developed for other indication. They found their usefulness in animal model and they've been developed, but they're far from being optimal. And usually what we do in drug development is we are targeting One pathway, one enzyme, and we find a good inhibitor and we see, and then we check what's happening in the— first in the animal and then in the patients. We are actually, I think in our case, we've been very lucky. Like I said, we were developing this Abi-171 for Alzheimer's targeting one specific protein. Along the development, we then start looking at the selectivity and we found out that actually the molecule inhibits not only that particular protein that is useful for Alzheimer's, but also another protein that is useful for the treatment of IPF for fibrosis. That's, I think that's where we explain, that's how we explain how the molecule works so well in IPF animal model. It's a molecule that different from the standard of care therapy, not only slow down the disease, but actually is able to reverse the disease.

Hmm.

Think about it. The animal actually They are able to increase their lung volume. They're breathing better. They are happier. I remember what my technician said, you know, if I go in the vivarium and I look at the animal, I can spot the animal that are on our drug compared to the other because they are the only one that are happy. They're jumping around and they breathe. So that was a very important statement that makes me realize how important is the drug.

Right.

That we are developing right now.

And it's more than the science and the drug, it's the regulatory strategy. So what have been some of the significant steps in that regulatory journey, the funding, the manufacturing, clinical planning that you've taken to move towards the clinic?

Well, we did all the steps that are necessary for drug development. Like I said, I have about 35 years of experience in all the different aspects of drug development. So the most fundamental one was about a year ago, We got the orphan drug designation from the FDA that kind of, it's a testament of how good the drug is. And also we just complete all the safety and toxicological study. And remarkably, we didn't see any adverse event. So that's also, it is extremely important because like I said before, the drugs that we have right now, they're not really efficacious, but also they are devoted of a lot of side effects. So At the minimum, if you can develop a drug that has the same level of efficacy, but it doesn't come with all the side effects, it's a win. It's a win for the patient. And we are now at the position that at least in preclinical, we have no side effects and we have very strong efficacy. And so that's why we think we are very well positioned to develop a very effective drug for IPF. So efficacy, as I said, orphan drug designation, efficacy, all the GLP studies are done. So the next milestone, be filing the IND and then jump into clinical trial to see how the drug behaves into first healthy patient and then patients.

And speaking of being well positioned, Avanti Biosciences is part of Connect's 2026 Cool Companies. And that's all about highlighting the startups with the strongest potential to help them build visibility, relationships, momentum, and hopefully raise funds. As you look towards that next stage, What kinds of investors, pharma partners, clinical collaborators, funding, or strategic relationships would be most helpful for you right now?

Yeah, that's a good question. That's why what we did about 3 or 4 months ago, we hired a chief business officer, Jeff Trickett, which is going to help us to raise awareness and raise funds to pay for the clinical trials. Until now, I was able to develop the drug simply using a non-dilutive fund through the NIH SBIR grant, which is extremely, extremely Unfortunately, we are all aware that since summer of last year, the SBIR grant program has been stopped. Hopefully it will restart again in September of this year. So that will still be an option. It's going to delay, however, our progression to the clinic. So while we are waiting for the clinical trial to become— sorry, while we are waiting for the grant to become available, we are looking for investors, you know, venture capitalists with experience in funding clinical trial and biotech company like ours. And also we are hopefully to find partner in the pharmaceutical industry that help us like co-develop the drug. They bring the expertise and also the fund to basically move into the clinical trial. At the same time, we are also very fortunate that we have already established strong collaboration with clinical site. We are on our scientific advisory board, we have Ganesh Raghu, who is almost like the father of IPF. He's the first one who studied the disease, is the first one who actually was able to market pirfenidon and nintedanib, who are the first standard of care commercialized for IPF. Along with Ganesh, also we are collaborating with Brigham Young University doing all the preclinical work on animal models to study how the molecule works into the animal and understand the mechanism of action. And also we are working with Giovanni Ligresti at Boston University, which is one of the opinion leaders in PIM-1, the protein that we are chasing for IPF, and he's doing all the in vitro work using human tissue. So basically to translate the work that we are doing here to the patient on that side too.

Well, and we have one last question for you. It's the one we ask all of our guests on the Connect Current. Closing on our very Connect Current quote— or closing on our very Connect Current note, what drives your innovative flow? What stirs your creativity?

I would say the desire to find something new. It is something like the fire that I have inside me is really to search something new, like an explorer. I'm not an explorer that go out in the jungle looking for the lost temple. I'm not that kind of guy. When I am in the lab, there is a fire inside me, something that may be small or something that you might say it's irrelevant, I found it very interesting and that's what moves me. I mean, like a week ago, Giovanni gave me some very interesting news about an in vitro study that he ran and I said, oh my God, this is great. And I start going out of there and basically I spend the whole day working on that information and try to think about what's next. So definitely is the desire to find something new and hope to find a cure for these patients that I came to appreciate. And I know how important it is. And so that's also what moves me, finding new therapy for people that are in their need of a new therapy.

So you're looking for the hidden temples inside the human body.

Exactly.

I love that.

Yeah.

But don't ask me to go out in the jungle. I'm not that kind of guy. So—

Oh, excuse me. Luca, I want to thank you. This was a really valuable conversation. I learned a lot. And it was a great reminder That bioinnovation requires both scientific imagination and disciplined execution. Avanti's work shows what it takes to move from a deep understanding of disease biology towards a potential therapy that could make a meaningful difference for patients facing serious unmet medical needs. We're excited to have you as one of our 2026 Connect Cool Companies, and I really appreciate you joining us today.

Thanks for listening to the CONNECT Current. If you want to learn more about CONNECT and explore resources across San Diego's innovation ecosystem, follow us on LinkedIn or visit connect.org. We'll see you next time on the CONNECT Current, where San Diego's innovation story keeps moving forward. Thanks for listening to the CONNECT Current.