On a trip to Basel, Switzerland, Philip catches up with Stefano Portolano, CEO of the European firm Azafaros.

They chat about Azafaros’ massive $147M Series B round in May 2025, which is being used to develop a small molecule treatment for rare diseases known as lysosomal storage disorders.

Stefano also explains how rare diseases went in and out of fashion with big pharma, the revival of small molecule drugs relative to gene therapies and biologics, and his extensive experience in big biotech firms.

⭐️ ABOUT THE SPEAKER

With more than 20 years of experience in orphan diseases under his belt, Stefano Portolano joined Azafaros in 2021. He previously served as Vice President, Strategy & Commercial Operations at Celgene and Head of Europe at Ultragenyx Pharmaceuticals.

Stefano first received his Doctor of Medicine from Università degli Studi di Napoli ‘Federico II,’ Italy and carried out research in autoimmunity as an adjunct assistant professor of Medicine at the University of California, San Francisco, USA.

🔗 LINKS MENTIONED

• Azafaros website – https://www.azafaros.com/
• Azafaros Series B round – https://www.azafaros.com/news/azafaros-secures-132m-in-oversubscribed-series-b-financing-to-advance-phase-3-clinical-programs-of-innovative-therapies-in-lysosomal-storage-disorders/l211c14
• Joris Pezzini, Alira Health | Hottest Biotech Insights – https://flot.bio/episode/joris-pezzini-alira-health-biotech-trend/
• Marc de Garidel, Abivax | How to make two Billion-dollar exits (“smoothly”) – https://flot.bio/episode/marc-de-garidel-abivax-exit/

Transcript

[00:00:00] Intro

Philip Hemme: What’s quite amazing in the round that you had only, or mainly European investors? 

Stefano Portolano: I think in a way, this testifies to the fact that Europe is finally playing quite a big role in this type of environment. That’s, that’s to me great news at the moment. I think that’s maybe a bit of a revival of small molecules.

The gene therapies have clear challenges and biologics usually only target one disease. Small molecules such as niag, that actually have the potential to serve more than one disease. What has changed over the past maybe 15, 20 years, and even if it’s a rare disease, you need to come with good data. It’s a longer enough to say, Hey, I treated a few patients.

They seem to be doing well. It’s a rare disease. That that doesn’t fly anymore.

Philip Hemme: I’m your host Philip, and I’m the show. I’m doing the best European biotech to help you grow of the more than 10,000 rare disease that are affecting 400 million patients. Only 5% of them have a treatment. The European company, as Harris, reached the headlines recently with almost $150 million series B to treat a rare dismal disorder with a small molecule.

So I caught up with Stefano while in Basel. I didn’t know him personally, but I’ve heard many good things, especially through his investors. JO We talked about the recent progress in treating this disease among storage disorders. We also talked about Stefano’s background in Italy and big biotech, and why now is the best moment to build the biotech in Europe?

So here’s my conversation with Stefano, and please hit the like of follow button if you’re enjoying it.

[00:01:45] Azafaros’ origin and $147M B round

Philip Hemme: Oh, welcome to Stevan. Thank you. Thank you for having me. Yeah. So I wanna start with, well basically what makes Za first quite unique, at least in my opinion. I mean, you’ve raised a, a massive series B, almost $150 million, which is very rare in in Europe. And at the same time you have launched like two global phase three, which is also very rare.

So I’m just curious if you can just tell me how you feel about it, how it, how it went. 

Stefano Portolano: Yeah. Well, obviously it feels great and it feels like a big reward for the team and all the work that the team has done in the past few years. It’s, it’s not been easy. The market is selective, but if you have a good program with a good plan then investors will, will reward as they did with data farro.

And one thing I do wanna mention, I think it’s our lead asset in iob Star really comes from more than 20 years of research in the Netherlands down at Amsterdam Medical Center and Laden University, professor Hanza Stan Van Boel and Herman Cleft worked, worked on a library of molecules. And so the Nuba was actually engineered to have the features that it does, it, it’s not a serendipitous fine.

We feel the responsibility to take this to patients and make sure we demonstrate its efficacy and safety. 

Philip Hemme: Okay. That’s fair. I saw that. Even when it was spun out, it was already quite advanced program. Yeah. But also interesting that I think bio generational for the FBS early stage was very involved in the company creation or something.

Can you like go a bit more into the, the story of like how it actually came about? 

Stefano Portolano: Yes. So I mentioned Professor Hans Arts. So Hans was at in Amda Medical Center. They moved to Laden and he dedicated his entire life to lysosomal diseases and developing small molecules that could impact these diseases.

So and he knew Edward Van Vail at the bio generation Venture, BGV because also they had prior attempts to actually, you know, develop companies based on this, which didn’t pan out. And so ultimately, when he got to Niag stat and he realized that this was really quite a unique compound as a potential at, at that time, he went back to Edward and BGV actually put the seed money for, for the compound and to start building the company.

And this was in 2018. And then later of course, fion joined in the Series A together with biomed partners VC based as of here in Basel. Correct. Schrader. And, and so that was the initial series A investment, which took us all the way to basically starting the phase three. 

[00:04:39] Developing nizubaglustat

Philip Hemme: Yeah. And then the.

The series B I’m curious because that’s, it’s a big amount. I mean, I see it’s, it’s Fabian growth and, and Jato and Jato likes to do also also big, big rounds like this. But it’s, it’s quite a jump from the series A to the series B, like, yeah. But at the same time, I guess it’s what you need to run the two phase three as well.

Correct. But can you give a bit of the background of the CV? Of Yeah. How you 

Stefano Portolano: Sure. So, yeah, and we, so the series A allowed us to basically perform phase one and phase two studies. Phase one has the volunteers, which we showed safety. We showed target engagement. Specifically we showed target engagement in the central nervous system because we had some of these healthy volunteers, we took lumbar punctures and we could look at the cerebral spinal fluid CS, F, so we could see that the drug penetrates the brain and engages the targeting the brain.

So the phase one was successful. We then moved into a phase two where we actually treated some patients with GM two Gangliosidosis and the PNE PC. And this was the core study was actually a, a dose selection study to really identify the right dose for a phase three study. And obviously then patients after the core initial three months rolled over into an extension phase where all patients are receiving drugs.

And now we’re also looking at the clinical outcomes. In an open label fashion in these patients. So all this really poised us to start the phase three studies. And we had basically moved forward. We had selected A CRO, we had initiated regulator interactions, and we had approval already by the European authorities for the clinical trial.

This was end of last year. Okay. So at, you know, the inflection points were there. And then of course, to run two global phase three studies, you do need quite a significant amount of money. So that’s, that’s how the whole came about. Now, this was an oversubscribed, as you know, okay. And that was because J two and four, beyond growth believe in the potential of this drug.

The asset actually could based on the biology, could actually impact a number of different lysosomal diseases. And so that’s why J two and four bium growth decided to actually provide even some additional funds to expand to additional indications beyond the ones of the phase threes. Several questions on what 

Philip Hemme: things I wanna jump in on what you, what we just said, but what the first one is, I guess as it’s a que, I mean, it’s a rare, this disease, I guess you also can run with, with quite a, a few number or like a, like few number of patients I guess.

And you can run it a bit faster as well. I can imagine. How fast Yes and no. Yes. 

Stefano Portolano: Faster. No. So, so I can tell you the phase three studies are they will enroll 75 patients each Yeah. Right. And us Europe, I guess if it’s US, Europe, and man, it’s actually global. So we’ll include Canada, Latin America Turkey.

We’re actually also looking at India. So we’re not running in Japan. Okay. So Japan, we’ve not explored yet how we, we are doing it right now. Yeah. If by including Japan, we can actually get a face registration there. So so it’s, it’s two global studies. And that’s why we still have a, a quite an ambitious target in completing enrollment.

But 75 patients for a rare disease is actually quite a large study. Okay. One of the largest actually in the end will be for these indications, or I should say the largest large these indications, 

Philip Hemme: but still way smaller than oncology or correct cardiovascular, whatever. Yes. Yeah. Okay. And okay. And actually you mentioned also on like expanding through disease.

What, what I saw in the pipeline, you’re, you basically have, it’s a single compound, single asset, very focused on those single assets. But then you’re trying to go to several indication. That’s correct, correct. Yeah. Correct. And why not? Like, expanding a bit or like, like having several assets. So you, 

Stefano Portolano: so we do have another asset which is in preclinical phase much, much earlier than, than Iub.

Alota. And that also comes from the University of Laden. Okay. And this is actually a clinically validated target in bone diseases. And so we, we have funds in our series B to also take that asset to a, to, to the clinics. So yes, 

Philip Hemme: mold disease as well for the bone 

Stefano Portolano: It, it we’re not disclosed. So it, but let’s say could be, that’s why not it’s stay tuned.

Indeed. 

Philip Hemme: Okay. And, and going a bit deeper into the, the indication itself, because I mean, small molecule in the brain is always a bit, I mean, for, for things it’s always a bit tricky as well. Or can you just talk a bit about the disease itself and how, how the compound, like what’s the mechanism action?

Stefano Portolano: Yes. So let’s, and I think you can lump together in a way. Congo, COSI is, and Mann peak type C. So what happens, there’s a missing enzyme in the lysosome, and that drives this enzyme is supposed to break down, you know, large molecules. So because the enzyme is missing or deficient, then you have an accumulation of these molecules that don’t break down.

So the, the compound actually acts as a dual mechanism of action. One mechanism is actually to reduce the production. Of these large molecules. So even if you cannot break them down, you still don’t have such an accumulation. The other mechanism is actually by inhibiting a second enzyme in the pathway, and that has less of a mechanistic approach by simply reducing the production as an impact on the downstream effect of the disease, such as, you know brain inflammation and not, and you know, the synthesis of certain compounds that are toxic to the brain.

And that’s really what makes this unique. So, and these two different mechanisms which are together in Mitags stat, they both actually have been clinically validated because there are drugs that are either inhibiting one or the other already on the market. And so our working hypothesis that by combining the two we’ll be able to actually have a better efficacy and ultimately also better safety.

[00:11:17] Competition in Niemann-Pick disease type C

Philip Hemme: Okay. That’s what I was about to ask actually, because I think. How, how differentiate because some, some drugs are on the market. I think, I mean, I’m not exactly which one, but I think I know Al you have quite a lot of competitors and S disease. I think Alion is one of them. I think 

Stefano Portolano: Al former reform, they were Italian and JJ Yes, 

Philip Hemme: is one of them.

And I saw for, for NKC, you had quite a few approvals as well after the rest here. Correct. So I feel like that there is quite a few things. Yes. Yes. So how do you see it? I mean, except that the dual acting mechanism, how do you differentiate and can you actually have like a significant benefit compared to the against?

That’s all we expect, we said. Oh, so 

Stefano Portolano: there’s, there’s been on the market for quite some time, MIAD, which is the formerly now j and j drug. Now it’s generic. And we do share some similarities in the mechanism of action with Miad. However, NI Tobar studies. Several orders of magnitude more potent than Migos stat, and very important, it does not have an off-target effect that is typical of Migos stat.

Migos stat inhibits GI enzymes and therefore causes diarrhea in the vast majority of patients. It’s actually quite a you know, poor tolerability profile. We don’t have that off-target effect in Itta. Therefore, we, what we have, have observed so far and what we expect is a much better safety profile and a much better efficacy because it’s, it’s a much more potent compound.

And 

Philip Hemme: I guess it’s something that you take chronically, I guess if 

Stefano Portolano: Yes. Yes. So it’s our nsbi site is being administered once a day and we have developed an a presentation of oral dispersable tablets. So these are the very small tablets that you put on the tongue and they disintegrate on the tongue.

Okay, so also quite convenient. Yeah. Now this is important because many of these patients actually develop difficulty swallowing. So this is more than a nice to have organized presentation. Now, you mentioned that some recent approval for pxi in the US and also recently the CHMP provided a positive opinion to another drug.

Our clinical study will actually deliver much better data dataset if positive because we have actually an 18 months randomized placebo controlled study, and none of the other drugs have such a solid and, and strong design, which has been agreed with the agencies as well. So why, why not?

Why they don’t have it? Yeah. It’s a long story. So if you should ask them, so because one drug was by Zyme and their, their, their study 

Philip Hemme: zy didn’t really work, right? 

Stefano Portolano: That’s, that’s the one that didn’t work. And then they went back with additional, you know, real world data and then ultimately FDA approved.

And, and then the other one is is based on a three month study only placebo controlled. So that’s why if our phase three is positive, it will deliver much, much superior dataset to what’s out there at the moment. 

Philip Hemme: Okay. Yeah. Okay. Makes, makes it. Yeah. I like it. I like it. And I’m curious on the, ’cause on one thing, I mean, if, if we zoom out a bit also on Yeah.

On rare disease, it’s, I mean, it’s not that typical to have small molecules for rare disease, at least in my, I mean it exists, but at least from my, yeah. And what I hear more often is whatever, I mean, it says the gen enzyme, the enzyme replacement. Yeah. And then now more like gene therapy to fix some of the rare disease, and especially in the genetic.

So how do you look at it like from a even not just as a virus on the, on the field? Like how do you look at the small s in, in rare disease? Like 

Stefano Portolano: I think so it’s true that ZA replace me therapies. Is that what you know, where it all started? Right. And I’m, I was fortunate enough to be at Genzyme during the Zyme launch and so, and Frazzy launch and so on.

That’s of course a very straightforward concept, although of course it’s not very straightforward to develop and commercialize and produce. So, so and I think Actelion indeed was the first one to try to use small molecule to, to impact these diseases. And and it was relatively effective, although being the first it wasn’t, it wasn’t great to be all honest.

As I mentioned earlier, you know, CS still Blockbuster drug. I don’t think he reached bull blockbuster. No, no. And because the safety was really not that great. So and and then gene therapy was the other big wish. And I remember back in the days talking to any patient or family, they want the gene therapy badly because, you know, it’s, it’s a great concept as well.

One shot theory fix, and then it’s done. That’s, without going into it, the gene therapies, you know, it’s not being as easy as, as one may be expected. And so I think maybe that’s a bit of a revival of small molecules. And there, there are been, if you think about it, a few recent approvals with the small molecules.

And I think, again, it’s not easy either, right? You still need to, to be very penetrant and, and even manufacturing, which admittedly is easier than definitely much, much easier than gene therapy. That, but also biologics, you know, even small molecules have their challenges with manufactured. But I have to say that the moment, I think that’s maybe a bit of a revival of small molecules, and they are looking at it because the gene therapies have, you know, clear challenges and, and biologics the, the have also one limitation that biologics usually only target one disease.

If you do enzyme replacement therapies, that’s that one enzyme that substitute that, that enzyme that is missing small molecules such as niag, that actually have the potential to serve more than one disease. So from a, you know, business perspective, that may help significantly. Yeah. 

Philip Hemme: So, yeah. And I guess from also CNS type brain penetration molecules still way superior to biologics.

I usually still today, even today, like yes, I usually start having some brain carrier or whatever erect, but I think it’s still, 

Stefano Portolano: it’s like, you know, if it works, that’d be fantastic. But yes, even small molecules sometimes don’t penetrate the brain, right? So there are marketed drugs that only work on the visceral symptoms of diseases because they don’t cross the brain blood, brain barrier.

So but it’s usually easier with a small molecule. If you have a library, you can find one that penetrates the brain. 

Philip Hemme: So I guess that’s also one reason why you guys are also going after. I mean, why the small molecule, why you’re going after small molecules at the end, like, 

Stefano Portolano: yes, yes. Like I said, it was, that’s how it was developed.

The, you know, the researchers in Liden actually looked at what was the one that was penetrating our brain and had all the other features. So, like I said, we benefit of this like 20 plus years of research, and now we are, we have the fortune and the privilege to bring it to the clinics. 

Philip Hemme: I see.

[00:18:44] The small molecule revival

Philip Hemme: And, and how much is what I’m also seeing in, again, still a bit on the industry trend on small molecules, I see a bit more like, let’s see, whatever novel mechanism action with small molecules, whatever the, the protein degraders and a few things that I think didn’t exist.

Whatever, 10, 20 years ago or at least, yeah, it’s recent, which is quite amazing that even small mes when, I mean it’s been whatever, 50 plus years that you explore and that I would, I kind of assume that we’ve explored a lot of it, but you can still find a lot there. Novel things. Yes. So how, in your case, like how much, is it like kind of novel small marker discovery or is it, you could have done it before, it just was was like finding the right target and the right mechanism of action.

Stefano Portolano: No, I think you could call it novel. Very much so. And the, the mechanism was described earlier, right? So inhibiting one part of the mechanism was inhibiting the synthesis of this large molecule. That was, that was Actelion did back, back in the days. There was indeed a serus fine, by the way that molecule was initially developed as an antiviral, but then they realized was inhibiting this enzyme and they thought, huh, maybe we could use iter disease.

And that’s how it all came about. And then that, you know, led to a development of a number of these molecules that, you know, inhibits the, the, the, the substrate synthesis. The, the unique thing about nag, like I mentioned, that it also doesn’t, you know, inhibits an other enzyme which has an impact on inflamma inflammatory parts of the disease, which is very important.

So, and and actually when you look at animal models, the other compounds are functioning, maybe one model, but not the others. ZBA study is the only compound that could be, that was effective in animal models of both Mannix C and Gangliosidosis. So that’s why we, we know even from preclinical data that this is quite a unique, so in a way it’s, it’s not a novel mechanism, but in only another way, this we are bringing something new and which for investors is interesting because of course you, you manage some of the risks because you know the mechanism of action works.

Philip Hemme: Yeah. Okay. Yeah. Yeah. Okay. So you try, yeah. Yeah. And it’s okay. Now coming back to what you also makes sense to what you said is like your drugs approved that show that it works. But if you increase, I mean, but they have a tolerate profile that does not that high. So if you can show that something works as well or more potent and it’s motorable Okay, you can expand your, okay.

Yeah. That’s the concept. I like it. And then the, just the kind of the next steps, I mean, you mentioned the phase three is 18 months. Mm-hmm. Do you have what interim readout or is, is really like the out as a We don’t have a 

Stefano Portolano: planned, the interim readout. Okay. At the moment we, we could always add one with an amendment, with a protocol, but at the moment we feel that that’s probably the way to go to a really solid data point at 18 months.

And, and to be able to show and to demonstrate long-term effect of the drug, which is what we expect. We expect this to be a disease modifying agent. So in a way we want to see and follow these patients for 18 months to be able to say, look, you know, we have a long-term effect. And, and by the way, even in the phase two study.

We have patients that are stabilized for the first 12 months, which is already a great result in these diseases, but then they start improving after 12 months. So, and these are, these are small numbers of course, but what if you do see some effect like that, then we don’t wanna miss that by, by shortening the study to a lower, to a shorter duration.

So at the moment we’re looking at the 18 months. 

Philip Hemme: Okay. So this brings you to like early 20, 27, something like this, or first half of 2027. 

Stefano Portolano: Yes. End of 27. We should have we should approach readout. Okay, because you started, we start now we plan to complete enrollment next year. 

Philip Hemme: Okay. 

Stefano Portolano: Yeah. That’s last patient in plus 18 miles.

It brings you to M 27. 

Philip Hemme: Makes sense? Yeah. Okay. And then, and on the way, what’s the, I’m curious on the milestones, I mean, except just executing, executing unrolling. Yes. Doing all the clinical trial, but what’s the, the next milestones? 

Stefano Portolano: So we’re clearly enrolling the study. I mean, now there are what, what we need to do in the next three years.

The first, second, third priority is enrolling the study. So the milestones are complete enrollment. And once that’s done, you know, keep patients on, on study and make sure we get enough patients at the end of the study. So, and we’re in a very good place there. Now. We are more and more sites being activated.

Patients are showing interest. We actually receive patient’s inquiry from a number of different channels. So we feel quite confident that we will achieve our, our goal to complete enrollment next year. Now on the other side, we’re also looking at some more strategic view with the additional indications.

So, and we haven’t disclosed yet, but we’re looking at two or three different options of additional studies. And the idea would be to do to perform one slash potentially two studies to demonstrate with a clinical proof of concept that the drug could work also in additional diseases. So by therefore adding additional value to the, to the assets.

So, and that part is more strategic. We also wanna speak to the agencies to understand what, you know, FDA and EMA would be more open to consider. We’re talking to KOLs to understand where we can make the biggest impact, at least additional indications. But next year we’re gonna firm our plans that we’re gonna get started with additional indication studies.

Philip Hemme: Okay. 

[00:24:29] Keeping options open

Philip Hemme: It sounds, yeah, sounds like you’re busy. Oh, Suzy. And I’m curious on the, on the company also, like, I mean, again, when you’re a single asset company’s always, I mean, you go a different indication, but I’m curious on, on the plan also, what’s the vision of the company? Is it like to build a bigger biotech?

Like where you were at your, you know, whatever Tic Celgene you said you men Genzyme. Is it the goal to build like really a commercial company and you, I mean, you could go commercial probably with the funding you have, or is it to, 

Stefano Portolano: so the funding actually is up until a data readout and filing. So we, we can complete the studies, including the positive data, I guess.

Though we are, we’re open to a number of options. And I think importantly, the option of actually being dependent, it’s actually on the table because we’ve raised diseases, the funds you need to actually launch are, you know, within reach of an additional series or something. So we, at the moment, we don’t have a set option.

We’re focusing on enrolling the study and execution. The, the funds that actually back us are quite resourceful, if I can say. So that’s very much an option, like others on the table as well. So let’s, let’s enroll the study, get the data, and then we can make a decision. 

Philip Hemme: I think that’s, that’s one thing that, that came up quite a few types on the podcast.

Like in, in biotech, you want optionality. Correct. So you wanna see a fundraising one. Fundraising, I-P-O-I-P-O, even slash fundraising. You want have the fossil exits, you want, have deals, you want, you’re able to go commercial. I think you’re, you guys are probably in a pretty good position as well. 

Stefano Portolano: We are.

And, and I see my job as a CEO very much to what you said, to keep options open, make sure I don’t, I never have only one option, because if that fails, then you’re, you’re left to hang, hang dry. I think the other thing that is worth mentioning, like I said, the actually the option to launch and be independent is viable, is not out of you know, out of the real reality.

But also it’s important to emphasize that, you know, there’s quite a number of companies on the other hand of the spectrum, the ye and a deal that have committed themselves to rare diseases. And, and they, and they do need to reach their pipeline because they have limited or no internal research.

So there’s a number of companies, it’s not much more than a handful of companies that, that are, you know, fit the description are very much interested in these type of assets. And many of these companies are companies that actually. Prefer to invest additional monies for de-risked assets IE assets with a positive phase three.

So that’s why we’re in a very, very good place. I, I think I will be in a position to actually pick the right option together with investors because ultimately that’s the decision 

Philip Hemme: of course. 

[00:27:23] Europe’s growing role in biotech investments

Philip Hemme: And I guess I wanna talk a bit more on the rare disease market as well, but mm-hmm. One specific question is, so what’s quite amazing in the round that you had?

Basically, I think only, or mainly European investors. Only European investors, yeah. Only. Yeah. And no American investors, which usually at this fund size, you have one, at least one US investor coming in. So I guess you also can tap into this bucket for next round as well, later round. And why didn’t you go for a bit more like.

Or you looked, 

Stefano Portolano: but it just, it, it, that’s how in the end, the, the, the round came together, right? I mean, we were talking to US investors, but then j to came forward with the, to lead and then for beyond growth. And I think in a way this testifies to the fact that Europe is finally Yeah. You know, playing quite a big role in this type of of environment and making sure that even European companies don’t necessarily need a US fund to do such a big round.

That’s, that’s to me great news. Yeah. And it, it, it was just, like I said, it was nothing specific about US Europe. I think just when you. J two comes in for billion growth comes in then it, at some point it was hard even to find space for everyone who wanted to be in. So like I said, problem, a good problem to have.

It was not anything specific that we didn’t go after the US market. 

Philip Hemme: Okay. Yeah. And I guess that end is also, it’s a matter of fit with buying personal fit, but also a matter of terms. I 

Stefano Portolano: can so very much, 

Philip Hemme: which is not the, that discussed openly in, in biotech, you know, the valuations are not, it’s, I. Not disclosed, usually evaluations versus in tech where people always disclose, okay, I raised that, whatever the open AI at 300 billion and like truth which is funny, and biotech is never really disclosed that.

I never, we can talk about this after, but then I never understood exactly why. But I dunno, 

Stefano Portolano: as a sideline, I don’t know. Yeah. But it’s true. It’s, we don’t disclose. So, very true. 

Philip Hemme: You, you, I mean, not just for, for you guys, but like in general, you like what? Like 

Stefano Portolano: I don’t recall that they disclose evaluation, you know, 

Philip Hemme: nobody.

But why is it, is it for like to negotiate the 

Stefano Portolano: exit afterwards? 

Philip Hemme: You 

Stefano Portolano: don’t want to disclose or, it’s a good question. You, you, you got me there. It might be, we might be, because that drives clearly the expectation and people know what you expect at the exit, so they don’t wanna disclose the cards.

But, you know, that’s a good question. I’ll ask Gito for being growth next time.

[00:30:12] The rare disease fashion

Philip Hemme: That’s and on the, to what I said on, on going back into rare disease, I think, ’cause I, I feel like rare disease, I mean, you, you mentioned I guess some big biotech, big pharma that are very interested in, in filling up the pipeline and are still very active in rare disease. I mean, I, I don’t know who, who we are actually thinking about, but what I, I saw that some, I mean the big guys, whatever, the still the gen ano Genzyme, the what’s the ast, the Alex and AstraZeneca and, and many more.

I’m just curious on, on how, what’s the sentiment on the, on the rare disease market? Because I feel like, especially on like ultra rare disease, I mean, I’m not talking about oncology rare, rare oncology, which is a bit different, but ultra rare disease. Like what’s the sentiment there? Because I feel like.

Was like not, I don’t know if it was a peak, but was a gen acquisition and an act election acquisition was like really big and maybe like it fluctuated a bit or what’s the 

Stefano Portolano: No, I, I think what happened was that there, there was a peak, it became a bit of a fashion, in fact is a word. And so Pfizer had a rare disease unit and, and GSK had a rare disease unit.

Everybody had a rare disease unit. And then this big pharma realized that the business model doesn’t really fit their business model and the effort they need to make to mark to do proper marketing and commercialization of a rare disease. It’s, it’s not good in their strengths. Right. So they. Basically came out of the rare disease, ultra rare disease, like you say.

However, there’s still a few pig pharma that have a rare disease interest and committed. You mentioned election, AstraZeneca definitely Sanofi and Biogen as well has some rare disease interest. But then there’s actually quite a number of, of mid cap or, or even some private companies that have that very much, you know, that rare disease focus, ultra rare disease focus.

And that’s quite obvious because for smaller companies, that actually is a very interesting business model because you can actually do good business without huge investments. And it is actually quite motivational, I think, for the teams to work in rare diseases. So, so I think, I think some people believe there’s less of interest now, but what happened, it was really that a few companies that went into it.

Then back to realizing was in their business model. But there’s quite a few companies, I would tell you it’s, I I could list these in more than 10 that have focused on rare disease and they do need additional pipeline because they have limited or no internal pipeline. Okay. Yeah. So, and from a regulatory perspective, I think what you see is that there’s still quite a few being approved.

FDA now has made for, for a number of years and now even under the new administration, is continues to message that they want to accelerate and, and look at rare diseases approvals in a different ways. Recently they approved drugs without a control study, right, with an open label study. And they specifically said, because in rare diseases you don’t always need this.

Similarly, the MA does the same thing. So the regulator environment is still very positive. And I would add even from a pricing perspective, you know, what you see in terms of pricing, especially in the US is still makes it commercially very viable. So I think the business is there and it’s, you need maybe what has changed over the past maybe 15, 20 years.

And even if it’s a rare disease, you need to come with good, good data. It’s no longer enough to say, Hey, I treated a few patients. They seem to be doing well. It’s a rare disease that that doesn’t fly anymore. You, in fact, we are running a gold standard study, if you wish, with randomized placebo control long term.

Philip Hemme: Yeah. And how, how much is it like a. Fashion thing in big pharma. I mean, they always love to go about whatever this, and now it’s like all the GLP ones and was oncology. Yeah. There’s a bit of anti infect, anti antiviral. Was was, was COVID, how much is that? Is that part of it? Like just of like, you know, big pharma following the trends and following each other?

Yeah. 

Stefano Portolano: I, I think when big Pharma went into it was a bit a trend thing and, and that’s why they walked out of it. And I think they did the right thing. Not, not because there’s nothing wrong, it’s just that it was too hard for them to adapt their business model of large indications to very small indication.

You know, everything is different about it. The, the, you know, the clinical development is different. You need to. We ha we know every single site that is in our clinical study. We know how many patients we should expect, and we know other patients in the country, you know, how we can refer these patients dealing with the early eyes, especially organization as well.

We work very, very closely with patient organization, not for sometimes. And and I have to say we’re privileged because we have great relationship. We have a person actually dedicated to work with patient organizations. She, she’s great lint and and, and, you know, it becomes a true partnership because ultimately you are in it for the same.

We want to bring a drug to patients. Patients want a drug that can help them. And, and as long as you’re transparent and you’re, you tell them why you’re doing certain things, even if it’s sometimes things they particularly don’t like, like running the placebo controlled study. Patients don’t like it or we explain them why we do it, and ultimately they understand and, and, you know, they, they become.

Again, you’re a partner and they wanna help you enroll the study. So, and then commercializing such a drug is very different than what you do for cardiovascular or oncology or something. Right? It’s, it’s, again, there’s a much more personal touch with the physician and, and the decision to start treating a patient with a rare disease is a much more complex decision that needs a very different approach to commercializing.

So it doesn’t fit what, you know, these big pharma usually do. So I think it was, it was a bit of a trend at the time. 

Philip Hemme: And again, a bit, a bit not that challenging, but a bit also the, as a background. But what I remember is like, basically when I finished my studies, it was not that long ago. I was in Boston and was basically at the time of the GenOn acquisition.

And I remember it was like, okay, the whole like big pharma model is changing. The blockbuster model is gone now. It’s only like a lot of rare disease and more like the. Hundreds of millions versus blockbuster. And then we talk with, with one guest on the show with, with from, from Ali. And he, and we basically think, but now, I mean almost the opposite happened was whatever K truer, she, it was even Blockbuster is back.

Yes. Whatever this last year was, whatever, 20, whatever, like 25 plus billion revenues. So is it at the end, I mean, I’m just kind of thinking out loud, is it like 10 years ago there was kind of a less opportunity to do blockbuster drugs and so okay, we go more into rare disease, but actually what happens that there’s still a lot of opportunities.

Of course, as a big pharma, you’re chasing the bigger opportunities. Yes. Is it also a bit of this that happened? Like 

Stefano Portolano: maybe, I think so actually, because I think, look, nobody wanted to touch obesity until some time ago, and now everybody wants to be in obesity. Right. I think I, I think, I think you’re around to something.

I think in fact they, there was a bit of a. How can I say, you know, like, type of social responsibility during the rare disease, we help the rare patients a nice thing. Which, which is true. It’s, it’s beautiful. Yeah. And big pharma wanted to be there, right? So, but then they, like I said, they realized this was too much for them and additional blockbuster opportunity came about.

So it was maybe a bit of both that happened. And and yes, I think, I think in the end, this is much better suited for a mid com mid-size company that doesn’t wanna build a huge commercial organization to market a cardiovascular drug or a, or an obesity drug. And therefore it’s, it fits and, but they have, you know, resources, they have the the cash resources and the human resources to actually do this in rare diseases.

And it makes much more sense. 

Philip Hemme: And the, yeah. And one thing you mentioned also on like the, on the pool that is. Maybe facilitate it little bit easier. I’m curious on like, but then you mentioned you need to have good data and, and the pricing sometimes makes sense. I’m curious, can you talk a bit on the, the relationship between all of them?

Because I feel like in rare disease, quite a few biotechs, they have their approval, but then it just doesn’t fly commercially, maybe because the data are not good enough or because commercial is, is harder than expected or whatever. Like, yeah. What, like, can you talk a bit about this, like the relationship?

Yes. And, 

Stefano Portolano: and as, as you know, my past is a lot in commercial as well, so I, I carry some scars on it. So, so I think again, what happened since the very early days of rare diseases where, to be honest, nobody thought that this could become such a, you know, large, you know, investment you came with like. Few patients treated, they gained some open label studies.

People thought like, yeah, whatever. It’s a rare disease. And payers did the same. Payers said like, you know, I have bigger fish to fry. I have cholesterol loading agents and rheumatoid arthritis, whatever. It’s a few patients go ahead and get the price. That has changed dramatically now. So from a regulatory perspective, yes, they do wanna look at rare diseases in a different way.

And, and, and sometimes they actually help you. And, and for example, in our interactions with the agencies, they always stress the fact that they will look at the totality of data. So we plan to hit the primary endpoints and go with a positive study. But the agency has signaled that, you know, they will look at the, all the dataset and, and lack it done for other drugs.

They will potentially adopt flexibility in approving these drugs. However, after that, you need to deal with payers. And, and what has happened is that rightfully many companies have tried to work on surrogate markers or tried to work on innovative endpoints because by definition you have few patients, you have very little data on natural history.

So you need to be creative around your clinical development. And that may work with regulatory agencies. Sometimes though, or, or oftentimes when you go back to payers and payers say, like, this endpoint doesn’t really tell me that you’re impacting the clinical outcomes of the patients. So the, the, the pricing conversation becomes very, very difficult.

And I think, and that’s why I feel very confident about our program because we, like I said, having a randomized placebo controlled study 18 months. So we’re, you know, you can do any better there. Our primary endpoint is a clinical endpoint. We’re not using a surrogate marker, or we are using a, a, a validated scale that measures ataxia in these patients.

So with a fa, with a positive phase three, we can go to payers and say, we improve this patient’s clinical outcomes on a longer term. And we have showed with a placebo control study. And, and so the value with that, we will be we’ll have the tools to argue the value of what we bring to these patients, even with payers.

Yeah. And if that has become more and more challenging because payers now see more and more of these drugs coming and, and the price per patient is high, which of course it’s understandable because it’s few patients. You need to have a higher price per patient. But it has also a bit of a psychological package with it that payers say like, oh my God, you’re charging that much for one patient, and so on and so forth.

So, but if you have good data. With a well-designed study then, like I said, you have the tools to have that discussion and, and therefore, I, I’m very confident that ultimately with a positive phase three, we should be able to actually get a premium price. 

Philip Hemme: And, and I guess as a, as a biotech specialized, but even as a pharma, you, you want to have a rare disease, which is not too rare.

Easy. I guess you want to have a, like not, I mean, I dunno if you can call it a critical size of patient, but you want still have enough patients to make the business case basically. Yes, I can imagine. 

Stefano Portolano: I can. So yeah, of course we run, you know, revenue forecasts and I think in our case, the fact that we can target more than one disease helps a lot.

Yeah. Because maybe if you only had one of these, the commercial case will not be perhaps vi viable. But they are looking other companies at rare and rare indications and you’re now also hearing a lot about N oh one. So my personal belief, I think when you look at like this. Super alter, rare, I don’t know what we’re gonna call it, right?

End of one or like n of 10 worldwide, you need to think of as different ways to, to make it viable to investors. Or maybe it’s not gonna be investors. It is gonna be a different type of funding because I, I, that is impossible to make it viable commercially. But you know, with the current pricing environment and the type of epidemiology and prevalence we have for our diseases, this makes it actually a very interesting business case 

Philip Hemme: because how many patients are we talking per year or So?

Stefano Portolano: I’ll say Europe, us maybe prevalence in Europe, US for Niemann peak type C we estimate been about a thousand patients, US a thousand patients Euro. Okay. So it’s so crucial. It’s not very, very, and Ferando, COSI is about half of that. So about 500 in the US and 500 in Europe. Yeah. The other important things perhaps about what’s newly diagnosed per 

Philip Hemme: year, 

Stefano Portolano: this is prevalence.

No. This is actually actual prevalence operation. Yeah. And it important to note as well, that also other regions which, you know, the case is usually built around Europe, us, but for example, Latin America, it’s a place where you have large countries. We have lots of patients. Potentially maybe even higher prevalence because of some founder effect.

I haven’t found any scientific data here, but it, it, it may be a way, but regardless, and those are also good business opportunity and, and companies one, one after the other have shown that you can build a strong business in Latin America as well. It takes a longer Of course, yeah. Than, than US and Europe.

But ultimately and I’ve, you know, companies I’ve been at or other companies, they’ve all built some relevant business in Latin America as well. 

Philip Hemme: Okay. That’s what interesting. Yeah. So you can really go global again. That, and it makes sense also for you. I was also one, one thing I was wondering is like why, why you clinical for you go so global, let’s say Latin America or India versus focusing on whatever U five plus us.

But I guess that’s one of the reasons. 

Stefano Portolano: So one of the reasons, one is to make sure we enroll the study in a, a reasonable time, but the other one is to build. The, the knowledge in those countries so that once the drug is launched, then you don’t have to start from scratch with, you know, having experience in that particular country.

Philip Hemme: And I guess even if the approval, I guess. Latin Americas, they will probably follow the decision of EMA and and FDA. But if you have local patient data, and if, I guess, I guess it makes 

Stefano Portolano: also the, the pricing much easier. It helps. And having the PIs knowing the drug already and how it works and how we use it.

So, and, and yes, Brazil follows quite a bit. The FDA, there are, and there are also incentives in Brazil for rare diseases. If you file early, you can actually have some fast track. So the environment is actually very positive for, for rare diseases as well. 

Philip Hemme: Actually, that’s one thing I was wondering, which I guess you have also fast track already.

We 

Stefano Portolano: do have, we have very pediatric disease designation, so both Europe and, and, and us. So this has been recognized as quite an unmet need. 

Philip Hemme: I guess that’s not, I mean, I don’t know how easy it is to get, but I guess if, sure. If you ever. Let’s say a potent candidates n rare disease, I guess you get it quite easily.

The, the fast. Yeah. 

Stefano Portolano: You have to, you have to show some fast track and orphan designation and you show some data, but non-clinical data is, is enough. In Europe, when you apply for marketing authorization, you have to confirm the orphan drug designation. So it’s, it’s, it’s, it, the bar is lower than getting the drug approved.

Yeah. But it’s not like as easy, you just say, oh, I think it’s gonna work. And it works. So does, it does take some work. 

Philip Hemme: So there’s drug development still. Yeah. But I guess it’s just easier than to get it into, like in onco, in a rare oncology, I guess it’s harder to obtain fast track and, and rare disease ations and, you know, I, I would’ve more ultra aware.

Yes. And on the, okay, and on the pressing, I’m just curious on, because what you said also that payers now that look and there’s more and more rare disease, which I guess. If you look at the single rare disease, it’s still a small amount, but if you do the, the cumulative on all the rare disease, I guess the amount starts to be much more significant.

Right. I guess if you take just the Redis bucket, then it becomes, I guess similar to other like disease bucket, I guess not oncology, but some other, like, whatever. I don’t know. CNSI don’t know how big is the bucket, but I guess you start to have similar, like yes. I don’t know the range you 

Stefano Portolano: last I looked at it.

The rare diseases altogether were still a quite a small percentage of the drug expenditure in, you know, major markets. So maybe if you look at specific therapeutic area, maybe becomes compar comparable to all rated diseases. But at the moment it is not that this is becoming like 50% of drug expenditure.

Like I, last I checked was like single digit, a single single digit percentage. So like I said, it’s more that. You see so many that payers are now not so forgiving. And so they still wanna see good data, they still wanna see clear endpoints, they still wanna see clinical outcomes, and, and the therefore it, it is more challenging.

But like I said, if you have good data, good, more well-designed studies, then you will achieve a premium price. Yeah. 

Philip Hemme: I’m curious about it because we talk, and I have to ask kind of, but we talk quite a lot on the, on the podcast with some guests on basically where is the market opportunity. And basically there was kind of anonymous that most of the drug reimbursement is in the US I guess for where this is.

It’s also the case. So for you guys, how, like, I, I remember one was like, was Ivax actually before the the phase three data which I think he said, mark Dell said like. I think 70% of its market is basically in the us That’s also why you focus quite a lot on, on the us. For you guys, is that like a similar range or, I mean, I guess in pacing population it’s not but in in like Yeah, like a business industry, is it?

Is it ML? 

Stefano Portolano: Yeah, so US is still, you know, the leading market clearly now revenue forecasts. We expect the US to carry majority of the weight. But Europe and other countries, like I said, do, and I think that’s my experience when I was in commercial, what happens, you have us. It, it’s, it’s bigger and, and faster.

Yeah. Then you have Europe coming and it takes a bit longer, but then it delivers quite good results so you can get a good opportunity. And then you can have Latin America, so in other markets as well. So in a way, if you have the right commercial strategy, then you have a steady, you know, countries that bringing growth, because then when us get to a point and growing becomes harder.

And so that’s where if at that point Europe kicks in and then Latin America kicks in, you have a, a good commercial strategy. Now. Things may change if pricing changes and if, you know, Trump has been mentioning most favored nation and of course the details of that need to be understood and, and it’s a bit unclear.

But at the moment we, we, we are in a good place because we have time to adapt to whatever will happen in the next couple of years, and then make the right decisions based on pricing Europe versus US if, if needed. So and like I said, the base is always having good data and therefore in, I, I feel very confident about having those pricing conversations, you know, throughout the world.

I Philip Hemme: like that talking with me.

[00:51:20] Getting personal with Stefano Portolano

Philip Hemme: I think it’s a good a good time to also, tend to switch to a bit more personal. I mean, you talk quite a lot about your commercial experience than before. I saw you were at, you mentioned you were at Genzyme, you were Celgene Genics. So basically big biotechs, big US biotechs.

But you’re always on the, on the European teams. Right. And it’s based time 

Stefano Portolano: in, in the US as well, with Genzyme. It was a couple of years in the headquarter, in in gen in Boston. Yeah. Yeah. 

Philip Hemme: Okay. I’m curious on, yeah, just maybe top level, some of the lessons you took from, from there. Like yeah. Very general question.

Stefano Portolano: So there will be a long list alert, so much Oh, but maybe I, I can think of a few things. So, so first of all, I think from Genzyme, what was really valuable there was really this, really venturing where no one else would venture. Right? And very clearly with the initial er zyme launch, nobody would think of marketed drug for a few thousands of patients worldwide.

And then they did. And er me, CO at the time late Erie, of course, had that vision and he, and he thought this could be done. And, and he did it. And he basically, that started this whole thing. And so to really not being afraid to, to venture into places where, you know, nobody else has gone yet. And take calculated risks, right?

So that’s, that’s one thing. Not to follow the path of least resistance and the easy path. Then I think, I guess that’s also where you have less comp. I mean, you have an opportunity and less competition as well. Correct? Yeah. Correct. And, and investments are not as high. So there’s pros and cons and, but you know, it takes some guts to say, I’m gonna bring a drug to the market for 5,000 patients worldwide.

I can tell you, and Harry used to say this story, all of me, that when he went to investors with that, investors said like, you’re crazy. You should change your strategy. This is never gonna work. So it proved them wrong. 

Philip Hemme: On Gen Z, the Luis, ’cause I read the biography of Fan Tamir. Yes. Think is an amazing book.

You read the book, I go, how much is it like the book versus your experience? How much is it like 

Stefano Portolano: it’s, it, it is, it’s quite there. It’s it’s Harry was really quite a visionary and I think, and then I had really have had the privilege to meet him, have meetings with him, and have dinner with him.

I remember when I was in Greece. And I was starting up the Genzyme affiliate there was my first role as a gm and he came specifically to formally sign the documents of incorporation of the new affiliate. And that tells you a bit how he was, he was like, he, he liked this like, personal touch with the team or with the patients and, and for somebody that at that time was leading a, I don’t know, several thousands people company, it’s, it’s not so to be expected.

So yeah, quite, quite a relentless person Harry. So learned a lot from him for sure. 

Philip Hemme: So, and then you, sorry, I didn’t want to interrupt. I mean, it was just a sec. 

Stefano Portolano: That’s okay. No, I think one thing that I remember about Celgene, first of all, an amazing experience. I joined Celgene and we were maybe. 20, 30 people all over Europe.

Within a few years. We were a few thousands. The company was, you know, generating, I don’t know, 1.5 billion in Europe alone. So quite a, quite an experience on, on managing growth. And I think one thing I learned there was that actually I don’t think we did anything very innovative around building the company.

It was pretty traditional, if I can use the word, strong medical, strong marketing, strong commercial. However, I think we did it really, really well. And so it taught me that sometimes you don’t need to necessarily be new, as long as you do things really, really well and you coordinate and you make sure people talk to each other and the teams are, understand the goal and embrace the goal, which was very ambitious.

Anything we did was ambitious there. So I, it was a great learning experience and, and like I said, managing growth, it’s been a bit my. My mantra there since then, that you, you need to expect that growth will bring change. You can say, oh, we’re the same as we were four years ago here at Zara, or whatever sanji you need to, to expect change and manage that change.

And because if you don’t manage it, then it will go a direction that you may not like. If you manage it, then it will go where you want to go. So you need to be very alert to that. 

Philip Hemme: I like that. Yeah. And Celgene, because at the end was, there was a quite focus on oncology, but at the beginning was more, it was 

Stefano Portolano: a hematology, hematology, oncology.

So we launched a Revlimid in multiple myeloma and mild, this past mild dysplastic syndrome. And then we per, we acquired Abraxis with Abraxane, which was for solid tumors that branched into solid tumors. But I think up and, and then at the very. Towards the end of my tenure at Celgene also we launched in the, into the INI space with Apremilast for psoriasis.

And then after that, it was acquired by Bristol Myers. So 

Philip Hemme: was, 

Stefano Portolano: oh, it was a hundred billion, a hundred business, a hundred billion. It was about, was a, I think it was still a good deal for BMS because they brought in good pipeline, good products steady cash flow. So maybe one of the last biggest of that size, 

Philip Hemme: this is almost there.

Stefano Portolano: I don’t, I don’t recall any that sucked because then Seattle Genetics was what, 40 or something? So 

Philip Hemme: not, definitely not as big. And you could have had, what is it, the, the Pfizer Astros that then went through, but that’s, I think was what would’ve been above a hundred billion. But That’s good. It’s a big one.

And so you, but you left before the qui acquisition? Yes. And then Ultragen, it’s. You were the head of Europe then, like 

Stefano Portolano: I was the head of Europe. I went, I did that. So when I was at Celgene, I was num employee number one in the Italian affiliate a lot, great experience. And then when I went to Genics, I was employee number one in Europe.

So okay. I started into a temporary office and started looking at I offices, hiring people in sciences, a lot of fun, a lot of work. And, and that I actually enjoy it very much. I know some, some people may not because it’s very tense and you’re taking risks. But I like, you know, building an a a team is like the most exciting thing that one can do as a manager.

So I really enjoyed that very much. And Autogenics I, I again, feel privileged that I worked with Emil Kakis, who’s somebody that really knows about rare diseases, has done it on, on, you know, on on, on his dime, even. And the guy is really quite, I, I don’t use this word lightly. He’s a genius when it comes to clinical development of rare diseases.

He really understands it and, and, and always has. And I, I talk to him on a regular basis and I pick his brain all the time, and he always, within five minutes, he comes with some idea that I hadn’t had. So, very, very interesting guy. I’m very, very fortunate to have worked with him, but to still have you know, be in touch with him on a regular basis.

Philip Hemme: And ultragen then. In the Bay Area and Yes. Yeah. You, I in just next to bi Marin, right? 

Stefano Portolano: It is right next to BioMarin. So the original office is Invato, California, so north of San Francisco. They also opened an office in Brisbane, south of San Francisco by the airport. Yeah. And they have a very nice building there in Brisbane.

So yeah, quite a, quite a good company. Interesting company now. So let’s see what happens. They have a few new pipeline. They should pan out in the next several months. How, 

Philip Hemme: how big is it now? Is it 2000 plus employees or something like this? 

Stefano Portolano: I, I don’t recall how many employees maybe around the numbers.

So yes, it’s, it’s a, yeah, mid-size. 

Philip Hemme: Yeah, it’s, yeah. And but now I also, I also understand because I was curious on this transition that you made from. Let’s say bigger biotech already commercial to now. Yeah. Earlier stage biotech. But I guess this like team building is, is actually quite an entrepreneurial experience in itself, like Yeah, yeah.

Stefano Portolano: Is it, is it is. Yeah. It is, it is different. So there are some similarities, of course. You are on your own in an office, you shop up first date, there’s no one there. Maybe you have a laptop that was sent to you by mail. But of course both in the Celgene situation and the Ultragen situation, you have a, a publicly traded company with let me think.

Celgene definitely with revenues already, Ultragenyx was approaching the time where they were having revenues. So you know, it’s an entrepreneurial, but you have, you know, somebody with big shoulders back in ui. This is different in that respect. And I think. It’s, it’s, let’s say it’s not for the faint of art because you go through ups and downs and you have lots of challenges.

And and you don’t have that backup of like, the US generating revenues or something. Here is like, if things don’t go well, it’s, that’s it. So, but again, that’s what I like. I really, and I can see that there are people that actually thrive in such an environment and there are people who are really not more cut for this environment and they should go to a different type of company.

And that’s okay. And that’s great. So that’s why different people thrive in different environments. So, 

Philip Hemme: and you, when you took the decision to, to join Aza you, you, you felt it this, like you wanted to try and you felt like you were, you were ripe for 

Stefano Portolano: Yeah. Yes, definitely. I would say I was still enjoying very much what I was doing, but it was becoming a bit more of the same.

And so I thought this is the opportunity to really shape the strategy from A to Z and, and, you know, shape the future in my own destiny together with the team. And so, yeah, I felt this was the right thing and, and also I could learn and because it’s not that you don’t learn anymore, but after 20 years in publicly traded US companies, it starts becoming a bit repetitive.

Here I’ve had to learn a lot of new things from raising funds to, you know, really being you know, deeply involved in clinical development, which I was before, but more potential. Right, right. Okay. You seem to enjoy it. I do. I do. Very much. It is the best job in the planet, so 

Philip Hemme: that’s cool. And how, I’m curious on the, I mean, you talked about the story of the company, but can you tell the story of like how you got in touch with us first and why you joined?

Stefano Portolano: It was, it was serendipitous this time. I was, I knew socially actually, somebody who was on the board from biomed partner being in in Basel. And, and now he was in Basel and Andreas, well, no, and he was on the board before and now, and then he left the biomed partners, that’s why. But no, but Andreas then went to Jto and then he left Jato as well.

And you know, Andreas, he was long time in Roche and so we knew each other through my wife and so on. And and at some point they were looking for a small buzzer, small buzzer work. And they did MBA together, my wife Andreas. So just to be fully transparent. And so at some point they were looking for, for a new CEO.

And so Andrea said, I know this guy is in Basel. He has an experience in rare diseases. And I also happened to know our chairman Carti, because Carlo was at Genzyme forever. And so we knew each other there. I think actually interviewed me when I joined Gen Cycle. So, of course Carlos said, of course I know Stefano.

And that’s, that’s how it all came about. Okay. I spoke to, to the shareholders and they, they believed in me, although I had never been a CEO of a, of a biotech and and so far so good. 

Philip Hemme: So far so good. Yeah, I like that. I think I interviewed Andrea on stage with my previous company, lab Biotech, which I founded and I think was, but the interview was in Zurich, I wanna say 2018 or something.

But then, and they were still in touch. Yeah, I talked to him recently for the, the, what was the deal? I, I buy, he did the exit. Yes. Yeah. Yeah. We talked a lot. It, yes. The amazing story in Exit also. It’s cool. Yeah. I liked him. And I’m curious also because, I mean, in. In Europe, as you said. Now maybe we can look a bit at Europe as well as, as I said, like, and connect it to your personal story.

Because I think now you have a bit more like, let’s say the experienced CEOs who have done it, but I can imagine when you joined like five years ago, even like a bit before, you didn’t really have like the biotech CEO was available in Europe. Who has done it, has raised, you know, a hundred plus million was probably, probably less.

So I guess yeah. At that time, I mean, you were also, I mean, I get just thinking on like, you had to, I mean, all the investors had to take a risk as well on, on finding the best true level CEO. That 

Stefano Portolano: true. And I think definitely I would say, because that is the a, a chronic challenge, let’s say for a VC backed biotech that’s talent.

At all levels. And it’s funny, when I was talking about this job with, with the board, they told me this and they said, look, you know, this is a talent it drives this market so you shouldn’t worry even if it’s a risky business you know, once you’re in it. And, and I believed, I thought they were just, you know, sitting the pill for me and just making it, you know, try to comedi, try to convince me it’s actually true.

Because, you know, when you look at the number of biotechs that start every year in Europe, I’m talking only Europe. It’s, it’s, it’s a lot. And, and many of them are in like France, Switzerland, you know, Germany and like that. And so if you think about it, all these biotechs will need to be staffed. And like I said, not everyone is actually cut for this type of environment.

So, and I’ve, I’ve witnessed it. I mean, it’s not easy to find the right talent for this. So I, I, that, that’s true, I guess at any level. So perhaps at the CEO level as well. So yeah, that’s good for me. That 

Philip Hemme: was good for you. And I was curious also the why, why Basel or why you’re still in Basel. I guess that answers part of the question, I 

Stefano Portolano: guess ahead on.

So yeah, the company is a Dutch company. My predecessor actually lives in Basel, so they set up an, an affiliate here in, in Basel in 2020, I believe. Okay. And then the, the, the, the buzzer office grew without any strategic intent. It’s just that there’s so much talent available in Switzerland in general and buzzer in particular.

Yeah. That then we, we have actually, I would say half of our team is paid in Switzerland. Okay. But we do have a diffuse team. We have our chief operating officer is actually based in London. We have, you know, people based in Spain and the Netherlands. We have actually a few employees and we.

Take full advantage of remote working opportunities. I, I’m a big believer that especially when you’re at a small team with such a focused goal you don’t need to be in the office every day. For sure. We do meet, of course, on a regular basis in person because that’s still important. But but yes, that’s, that’s how we came about the whole Basel presence.

Philip Hemme: Yeah. And I get, I mean, I think that’s also one thing we discussed on the, on the show is with some guests, like in what you just said of like, talent is a, is a, is a bottleneck. Yes. So if you hire across Europe, you just have a access to a much bigger talent pool. 

Stefano Portolano: Correct. Some of the people, many of the people that, that are based elsewhere would’ve wouldn’t have moved to Basel.

And so I would’ve lost that talent. So, absolutely. And I think it’s a great, great opportunity to, to, to take the advantage on that. 

Philip Hemme: And I guess for you, you didn’t want to move out of Basel to, to now the, not to the Netherlands 

Stefano Portolano: necessarily. He, I mean the, the, the office, I inherited this office by the way.

And so there was no need to move. And so that’s, I did ask the shareholders like, is there any reason to do it in one way or another? And the show said, look, talent is the most important thing. You have to write the right people. So that’s, that’s how we’re going, going about this. 

Philip Hemme: Okay. That’s good. And before we do a, like a quick fire, the, the last one is, is more like on your, even before you started in, in like, let’s say your career.

So you were. I think you’re, you did a PhD in Napoli? I, I’m a physician, yeah. Yeah, a physician trained in Napoli, Nepal. You grew up there or? I grew up there. LA and, okay. Hi. And then, and then you, you actually did your postdoc in, in San Francisco? Yes. Yes. And how, like, maybe quickly, but how, like, how was it, and how was the, the transition then to, to biotech like?

Stefano Portolano: Yeah, so as a physician, I had this dream of go to the US and work in research and, and again, I was at the right place at the right time. I professor at the time in Italy said, I need somebody to go learn molecular biology and that’s you. And I said, okay. So I went to San Francisco. I spent, I was supposed to be two years there.

I stayed longer, and then I became a, an adjunct faculty. And then the the, I joined the industry. That was really against serendipitous. I was looking for another lab and I thought I would be a researcher for the rest of my life. That’s what I was good at, at the time. I I was, had been successful.

But then I found out that they were, you know, looking for somebody in a Met Affairs role and in, in, in an Italian company at the time. So I said, oh, well, I, I give it the try. And then I spent three years there, and then I went to Genzyme and there was my, I really understood that’s was, you know, that’s what I enjoyed.

I had a great time, great colleagues, wonderful business. We were helping people and I thought, I feel that I’m doing more for patients here than I had could do as a physician or even as a researcher. So that’s why I found my, my calling. I was lucky as well. But you need that as well in life. 

Philip Hemme: Yeah, it’s a, it’s a good one also.

The, and impact you can have it, it also, I mean, as MD you can maybe treat, you know, a few patients, right? Per year. And if you develop a drug, you can treat a few thousands of 

Stefano Portolano: patients a year. Right? And, and it is just, if you enjoy treating patients, you know, luckily there’s a lot of people who enjoy being physicians and Linux, but I thought that this is really what, what I have enjoyed most.

So, like I said, I found my calling. Yeah, 

Philip Hemme: amazing. 

[01:11:11] Quickfire

Philip Hemme: So do a quick fight, which is basically like some quick smaller question or questions and, and some smaller answers. And the f the first one was the FI had one about small molecules, but we, we answered this one. Maybe one. Who is one of your biopharma heroes?

Except, except Henry Te. 

Stefano Portolano: Then next to next to him, I would, I need to keep two names. One is Emil, which I mentioned. Yeah. Emil Kakis has really pioneered clinical development of rare diseases. Harry pioneered the business side. I think Emil has been really, you know, his deep understanding of these diseases and understanding how you can address them.

I’d also like to mention our chairman Chetty, because he’s, he was a Jensen for many, many years and, and majority of the rare disease drugs that were approved at Jensen were under his watch. So he, he’s an asset to our company as well. 

Philip Hemme: Yeah, that’s good. One thing Europe should do to promote more entrepreneurship in, in biotech.

Stefano Portolano: Oh, huh. A few, but let’s say the capital markets are improving. I still think there’s too much regulation. Across different countries. So what happens then? You have a few countries that are leading the way. It, it’s not a coincidence that Pharos as a Dutch of French investors because those countries are really helping.

There are others. I think that if they could streamline that type of capital market availability and then downstream, you know, deal regulations, that’s, that’s also that, you know, some investors have that baggage on their side in other countries. So I think, I think that’s one thing. If I need to name, 

Philip Hemme: no, let’s go on.

What’s one of the widely held, why widely held belief about rare disease amongst, let’s say, investors or entrepreneurs? What is not true? 

Stefano Portolano: Not all investors, but some investors believe that this is no longer of interest for potential acquirers. And that’s the reason why we discussed earlier, because some big pharma walked out of it.

And so if you take a superficial look, then you say like, oh, you know, GSK doesn’t have a rare disease, so there’s no longer interest and it’s just, there’s an interest from other companies. So but there’s a lot of investors who actually understand that this is a very good opportunity. Still quite a few investors.

Okay, 

Philip Hemme: that’s a good one. One, one mistake you made in the past 12 months. In the past 12 months, 

Stefano Portolano: huh. 

Philip Hemme: Let’s see. 

Stefano Portolano: Oh my goodness. Yeah, I guess it was yeah, I’m not sure. I’m not sure. I think I. I think on the clinical trial, you know, usually the mistake that I tend to do is to, that sometimes you need to get more of your hands dirty into the operations.

And I like it. I usually do it, but sometimes I have other stuff that, you know, like closing the, I don’t say Rob or like a podcast. And so sometimes you need to know when it’s time to actually get in in the operations and work with the team and make sure the team understands what’s need, what needs to happen and, and, and provide help sometimes.

Right. So, so maybe, you know, that’s, that may be something that I have done in the past 12 months. Okay. So the balance between what you, the balance between the two and usually I, I err on the fact that I don’t get involved because I think the team is great. The team is doing fantastic job, but sometimes my presence actually can, can help.

Philip Hemme: And the details are still like, right. Yeah. Correct. The. One new habit that you adopted recently? 

Stefano Portolano: One new habit I adopted recently has been to really have even more, I’ve always had ongoing conversations with investors, but I try to keep that going even more because what happens sometimes, again, talking about operations, you get so sucked up by taking care of execution, making sure everything is okay, that you forget that it’s good to keep them involved and keep them abreast of what’s going on, of the challenges, the opportunities, the good news, and also good news.

And so I try to keep this as a regular touchpoint. Sometimes just, you know, reaching out and say, Hey, do you wanna have a chat? And so on. So outside board meetings of course. So there’s less suffice for the board meeting as surprises for the board meeting? Very much so. Yeah. So I think you told me it’s this week.

No, it is this week. Yes. Day after tomorrow. 

Philip Hemme: Yeah. That’s good. And your last one, like one advice to young life science professionals. Yeah. Finding your calling I think is, 

Stefano Portolano: yeah. Yeah. That first of all, do something you enjoy because if you don’t enjoy what you’re doing, there’s no way you’re gonna do it well.

So, and this is not new. I think Obama had the same, so I think, but it’s a pretty basic, but pretty important they do something you enjoy with people you, you can work with. That’s the other thing. The asset, the company’s important. The program is important. Everything else, but the most important things that you actually enjoy what you do and you enjoy working with the people you’re working with.

If those two things are not there, then you’re gonna have the best asset in the world. Don’t go there. So, and also be, things will come and, and I, I’ve been in places sometimes where I felt like I’m never gonna achieve what I want to achieve, whether that’s career or something. Ultimately, if you’re persistent and resilience, then things will cut the environment.

And Europe right now is really the place to be, I have to say. So things are very different from like 20 years ago when I was a young physician as a completely different, so there’s even more opportunities now in Europe than, than they used to be. So I think this is a good moment to be in life sciences 

Philip Hemme: and that’s a great way to finish the conversation.

Excellent. Thanks, Stefano. 

Stefano Portolano: Thank you. Thank you, Phillip. This is very much enjoyable. Yeah, so we should do it again.

Philip Hemme: I’m impressed by Stefano’s dedication to helping rare disease patients over his career. I’m also impressed by Stefan’s transition to a CEO of a biotech and his execution so far. If you’ve enjoyed this episode, please hit the like follow of view view button. Any of these actions will help give more exposure to the podcast to more people.

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Thanks so much for staying until the end and see you in the next episode.