Viraj Mane, PhD - Co-Founder at Lactiga

Welcome to another Founder Wisdom podcast. We have Viraj Main with us today. He's an entrepreneur, scientist, focused on building teams and technology at Lactega. We're gonna talk about that one, it's very unique. Viraj is the PhD, and, uh, yeah, Lactega, how can I explain that? It's a biotechnology company committed to pushing the boundaries of medical science, improving the lives of immunodeficient patients through innovative mucosal therapies. Um, Viraj is going to explain us a bit more about what that means. So welcome to Pod, Viraj. Tell us a bit more about yourself.

Great to be with you, Charles. Thank you for this opportunity. Yeah, in terms of, um, who I am, I'm a science nerd. Now it's kind of cool to be a nerd, but back in those days when I was a kid, it was not cool at all. But I did love the sciences regardless, um, from a pretty young age. And just one piece of you know, background, something I did as a kid that really brought me to where we are today talking to you is I remember Time magazine in the '80s. My parents would buy these magazines. You had paper magazine subscriptions in those days. And something, a topic that was in Time magazine way back, again, this was in the '80s, was the idea of gene therapy. And one person, one patient they talked about was a young boy named David Vetter, who was nicknamed the boy in the bubble because he lived his life in a sterile bubble because of a severe immunodeficiency called severe combined immunodeficiency, or SCID, S-C-I-D. He could never live an actual life outside that sterile bubble because of how vulnerable he was. And he actually died before I think he even hit his teens. So it tells you something about how severe that disease was. And I remember thinking as a kid, like, scientists could unlock something that could help a kid like David Vetter someday in the future. And fast forward many years, I did my PhD in human genetics at Baylor College of Medicine. Literally studying diseases including immunodeficiencies like what the boy in the bubble had. And then fast forwarding even more, I became a father many years ago, and many new moms are pumping breast milk and keeping them in pouches or bottles because they're pumping late at night or at work and they're not using it at that time, but you're keeping it to put it in a cooler bag and bring it to your freezer and keep it for when you need it. And I remember looking at those pouches thinking, these are full of antibodies, we know that scientifically, What if those antibodies could be functionalized into a new therapeutic medicine for immunodeficient patients? And that is the direction and the origin story for the company Lactiga.

And that is crazy. And what was your background before you launched the company?

So I had worked with entrepreneurs for years, actually in the Toronto ecosystem. We were just talking about Canada. And I had different roles at the types of organizations that fostered public-private partnerships and bringing startups and governments and large companies and academic partners and bringing them into grant-funded projects. So that was some of my role. And because of that, I was meeting entrepreneurs all the time. And as I'm sure you have the same feeling, when you're around entrepreneurs all the time, it's stimulating and it's, it's inspiring. So then you want to take that plunge yourself. So I'd had roles like that for many years before Lactiga. But even before that, I did grad school, as I mentioned. I did a postdoctoral fellowship at the FDA. Then I did another postdoctoral fellowship at the University of Maryland. And then I actually spent several years supporting the Department of Defense in their medical countermeasures portfolio as a technical analyst. So in all those roles, I was still deeply involved in the sciences, but I realized that I could take a different approach towards ventures and innovation, not being on the lab bench, but rather by putting together ventures and building strategy and outsourcing some of the earliest R&D experiments, which is exactly what the early stages of Lactigo were like.

And tell me specifically, like, why breast milk? Uh, we know it has antibodies, and is it because it's always like readily available? Why not cow milk, for example?

Like, yeah, that's a great question. So now we get into the biology. And so cows don't get the same germs that humans do, right? Like cows didn't get COVID-19, for example, or they don't get the annual flu strains that we humans get. But mothers who are lactating, they are getting those germs. And so those antibodies are representative of the germs that actually afflict humans. Whereas cow milk, first of all, you'd have to sort of drink like a raw unpasteurized version, because if you heat treat it, which is what pasteurization is, you would degrade all the antibodies that are in cow milk. So you wouldn't get that benefit anyway. But the species mismatch is the more significant issue, right? Cows aren't getting COVID, they're not getting E. coli strains the way we are. So human antibodies can protect humans from those pathogens.

And the breast milk is— has antibody for any human? Isn't it just like from mom to children? Is it like a custom milk for bad children, or can it work for pretty much all? And I'm guessing you extract the antibody from it. So tell me a bit more about the science in itself.

Yeah, I love these questions. You're exactly right. So a mother's milk, you can think, is optimized for her own child because they live in the same house, so they're facing the same germs. So her protective antibodies would be maximally effective for her own child because they're going to be protective against everyone in that family unit. But there's a long, long history of wet nursing, which just means a mother that is lactating is providing breast milk to a baby that is not her own. And that is safe, and it's been in use among humans for, you know, thousands of years. And so those antibodies can be effective even if the recipient is not the baby of the person that was producing the milk. And so that's pretty well understood. You know, there's been an informal market of sharing milk, but more importantly than that, there's a much more formal ecosystem of milk banks. So everyone has heard of blood banks, but not everyone has heard of milk banks. And this is a network of over 700 centers all around the world, with about 32 of them here in North America. And they function to secure the extra milk that mothers who generously have extra and very generously donate that to the milk banks. The milk banks can then collect that, pasteurize it, make sure it's obviously safe to be delivered, and then it can be provided to medically fragile babies. And they could have infections that they need to fight off, or they could be premature where they're just very vulnerable in general. For all these different reasons, medically fragile babies can benefit tremendously from human milk or breast milk. We started— meaning we at LactEga— we opened these discussions with milk bank directors, which I'm so proud of because it was such an early shot in the dark that we had to take. To reach out to these milk bank directors and say, we know that there's samples you cannot use for your purposes for a variety of reasons, which we can cover if you like. But since there's all these samples you cannot use, what if we use them to do the antibody extraction, just like you said, and to package them and formulate them into a novel biologic, a therapeutic that can be used for those immunodeficient patients? And that created this linkage between the milk bank and milk donation world and the rare disease community, which had never had this linkage before. And so of the many things of Lactiga I'm proud of, this is a big one because that just didn't exist. You know the phrase zero to one for entrepreneurship? That's very much what that was.

Right. And antibodies, how are they vested? Like, what's the alternative?

Oh, do you mean like how were they generated?

Yes, yes. Where do antibodies come from naturally? Because there are other sources and other end products that include antibodies? What's the classic way to do it?

Right, so we— if we're healthy and we're immunocompetent and we don't have an immunodeficiency, then we're all producing antibodies all the time, and they come from our B cells. B cells and T cells are some of the core components of our immune system, and B cells in particular produce antibodies. Those B cells can only do that if they're educated against pathogenic or environmental threats that your body's actually facing. So if you were never exposed to COVID, you wouldn't have COVID-fighting antibodies.. But those of us that had it or had the, you know, that's the point of the vaccine is to stimulate robust antibody production against whatever that target of the vaccine may be. Now, in our general lives, we're coughing on each other at the bus stop or on airplanes. So this is happening always in real time. And all the antibodies we are producing, it reflects that. It reflects all the germs or toxins or contaminants that we have fought off in our environment. And that's why human milk is already naturally abundant in those antibodies because the mother is facing those. Threats, and she's generating antibodies accordingly, and those antibodies are being passed to her baby through breastfeeding.

Okay, and you take that milk, and is the end form of your product a vaccine?

No, it's not. So the difference with what a vaccine does is it's meant to provoke and induce a strong immune response in your body that stays as a memory response. So if you face that same pathogen again, COVID-19 being a good example, your body will already have circulating antibodies. We are talking about immunodeficient patients who typically have poor response to vaccines in the first place because their immune system is already compromised. So they can't mount that strong immune response that the rest of us would get when we receive a vaccine. So to your question, what we're planning to do instead is to purify the antibodies out so it's no longer the milk starting product, it's purified antibodies. And you can formulate that into different compositions that can then be delivered to a person. The lead asset we're working on is a small nasal spray. So if you think of a Flonase, a small bottle, you just give it a squeeze and it shoots a small volume into that nostril. Then you do the same thing on the other side. And we project based on our early pharmacokinetics data that by doing that just twice a day for these immunodeficient patients, they can reconstitute the missing antibody mucosal immunity that they're not generating on their own because of their disease.

So these things, antibodies, they're separate from their immune system. They don't involve their immune systems. They're like natural B and T killer cells, like from your product in itself, and it doesn't involve their immune system whatsoever.

So the antibodies are purified from milk, and then they're delivered into patients with antibody deficiencies. And depending on the disease, they can be deficient in some antibodies or all antibody subtypes. The boy in the bubble, David Vetter, that I mentioned before, he had a very severe form called severe combined immunodeficiency. So he really had a very weak response of any antibody production. Some of the patients we're talking about, including those with common variable immune deficiency, they're also missing multiple antibody subtypes. And so that leaves them very vulnerable. So their immune system is severely compromised, especially at the points of entry that pathogens would most frequently get into your body. So number one, that's your nostrils, because now they can access your respiratory tract. Or number two could be the oral route, because then they can infect your gastrointestinal tract, the stomach and the intestines. So the vision here is to really replace using an immune replacement modality to get those antibodies from these pooled milk samples to reconstitute the missing immune layer in these patients because they cannot produce that on their own.

Got it. So you have like an army of soldiers ranking up in the nasal tracts and protecting from bad pathogens to enter. They get killed right at the gate, sort of is the logic. How can this scale Uh, what would be an industrial operation of this? Like, would you have to process, I don't know, hundreds of liters of maternal milk on a daily basis? Would you pay these mothers? Like, how can you scale this?

Yeah, the scalability comes from being very careful and deliberate and respectful in our outreach to the milk banks. As I said, there's around 700 worldwide, about 32 of them in North America. All of them have percentages that they cannot use for their own purposes. And that represents a scalable supply that we can divert into a biomanufacturing workstream to produce the biologic that we're talking about for our company. So we've been very fortunate to be successful in those early discussions with this small number of milk banks. But as our needs grow, meaning the volumes we would need, our need to build additional partnerships with those milk banks will also grow. And so we talked to them literally years ago about what that could look like. And our early advocates and champions and partners said, yeah, when you're ready for that, we'll together and we'll recruit additional milk banks so you can scale your supply up accordingly. So that puts us in a really unique and interesting position where we have all the milk we have needed for all the R&D we've been doing for the last couple years. And as we're getting ready to scale, which is happening very soon, we will have these partners to support that increased supply. And again, we're talking about 0 to 1. That's a relationship that has never existed— sourcing from milk banks to enable a novel biologic.

Can you mix all of these milks, or it's just like one pouch at a time?

They come from individual donors from the lactating moms, but we would then mix them, pool them basically. And the reason why is— it's a great question— is that you want to maximize the antibody repertoire that's in any given product. And the way to do that is you pool them at the top end, so every formulation that's derived therefrom is representative of this large master batch. If one pouch became one product for one patient and a different batch became a product for a different patient, they can be getting something a little too different, right? Because the antibodies are from totally different mothers with different exposures. So to smooth out those inconsistencies, the way you do that is by pooling them into a large batch so all the products are derived from that master batch.

But what, what if one is just like not— doesn't have like much antibodies, just dilutes the full quality of the batch?

Well, lucky for us, human milk, and especially earlier milk when the baby's very young, has a high concentration of antibodies. Exactly. Colostrum has extra high concentrations of antibodies. But all the samples beyond colostrum, you know, for the next months and years, they still have well-known, pretty high concentrations of antibodies. So there's no risk that this sample had no antibodies, so it was a waste and it was dilutive, because we would do an extraction anyway based on the methods we've already developed and patented such that the final product is a concentrated form of antibodies anyway. So the fact that the samples at the top end were diluted, if that were the case, that wouldn't matter at the end when you're concentrating them anyway.

And how much milligram per ounce of antibodies would there be in milk?

You can get about a gram per liter in terms of the natural concentrations of antibodies that are in human milk. Again, it can be much higher than that. If you were testing colostrum. And depending on the donor, it could be lower than that. But that's a rough average, which has been borne out by, you know, literally decades of literature studies looking at milk antibody concentrations. So fortunately for us, we don't have to guess too much about that. The average values are well known.

And antibodies, I guess— I'm guessing— I mean, they're proteins, but technically they're living things. So you need to refrigerate, right? And Um, what are the, the specs to keep them active and alive?

Yeah, so antibodies are molecules. They're not living things on their own. They are secreted by B cells, and B cells, you know, are living things that could be cultured in a, in an incubator if you were interested in like that element of biotechnology. But the B cells produce antibodies, which are large macromolecules. Once they're purified, at that point, as with typical biologics, as long as you have sufficient storage conditions, they can be effective and potent for a long time. And we've done studies leaving them at room temperature deliberately to see if they were stable, and they had a favorable profile at that. That was some of our earliest work that we put into our granted patents. And we've since looked at freeze-thaw cycles because many medicines, they wind up in the fridge at some point, or at -20°C, or even -80°C for really sensitive proteins that need to be stored in very sensitive conditions. And when we looked at freeze-thaw cycles, it actually didn't harm the potency and the efficacy of these antibodies. So they're durable in our hands, and we knew that. And it makes sense because milk antibodies are also very durable because they're literally being expressed through the mammary gland, fed to a baby where it's winding up in the baby's gastrointestinal tract and the stomach, which is literally full of acids and proteases whose job is to break down molecules and food components. So the fact that these antibodies are naturally resilient in that environment, based on that, we knew that we probably had a very durable form of antibody in mind when we did our own extractions, and that has been true.

You have to pay these milk banks?

We are structuring supply agreements with them because of course it's important that they are compensated for the contributions that they're making to us. And so that's one of our first discussions we had with them.

And can't you shortcut them and go directly to the milk producer, or are there laws behind that?

There is kind of a— I guess you could call like a gray market economy of— actually, some of them are bodybuilders that seek to buy milk samples from mothers who have extra, like on a Facebook page, for example. And the reason why is because many people consider milk, human milk, as a superfood. It's full of antibodies, it's full of nutrients. No, we are not going that route at all, just to be clear. But I wanted to give you that context that there are—

they pay for it, right? That's the point. Like, they—

that's right, that's right. So that system, which is totally different than what we're doing, you know, mothers who may have extra can meet people who have that interest because they think it's like almost a luxury food, or they're doing it for fitness reasons, such as the bodybuilding community. Uh, that's not our framework. Ours is to, again, what we're when we first reached out to these milk bank directors, we knew it was important to be, um, very enthusiastic and respectful of the very important work that they do. I mean, they're doing life-saving work for vulnerable babies.

So yeah, but the potential of paying pregnant women, that's— I think that's, uh, incredible. Um, why? Because some produce extra and they need money to put food on the table, especially like, uh, single mothers, right? And that would be like a means for them to survive economically. That very hard period of their life to buy diapers and food and all the baby stuff. I, I think that that would be— and I, I've talked with an entrepreneur actually that's going to be on my podcast for that. If you want, I can connect, uh, you to her. But she has an app basically in which, yes, uh, women sell their— it's like a breast milk marketplace.

Marketplace.

Yeah, I think that's, uh, that's super intriguing. Um, I'm just trying to see like the economics of it, right? So paying the breast milk, converting it, right, and putting it at scale, what would be the end price of the product, like that nasal spray, right? Let's say a nasal spray could last me a week or two, like what would be the cost of that?

Yeah, this is a great question. And I'll give you an industry benchmark in just a moment. In terms of our own pricing, this is like rapidly evolving information. We've been speaking to vendors and biotech manufacturers and formulations experts for many years now to understand these. It's very complicated because this hasn't been done. Like, everything I'm telling you, like the sourcing, the purification, the formulation, and delivery to these specific, uh, patients with these very specific diseases— all of this is new. So to price that, like, you really don't understand that until you actually start the manufacturing, right? We've gotten estimates or quotations from multiple vendors, so we have a ballpark, but it's very complicated, which, which I've learned over these last couple years. The really important benchmark that has helped us in some of our assumptions is that there is a product that delivers polyclonal antibodies to some of these immunodeficient patients I've been talking about, but they are derived from blood. And so the blood comes from blood donors, right? We've been talking about milk donors, but there are blood antibody products sourced from blood donors in blood collection centers. Those are already operated by the plasma biologics companies that exist around the world, some of the States, a lot in Europe. Um, some in Asia and some other countries. And we've actually spoken with a lot of them because they understand what it's like to start with a mixed human fluid— in their case, it's blood— to extract out the antibodies, to formulate that for performance characterization and stability, and then to deliver that to immunodeficient patients. So they understand that some of the different areas that we have to solve for our vision as well. And so that's the benchmark.

It's—

it was actually approved by the FDA back in the mid- 1960s. So there's literally decades of precedent behind the sourcing, the purification, the formulation, and the delivery. Those are injection and infusion products. Ours are not. So we're doing very, very different things with different antibody types.

And immunotherapy, right? Like, is that a market that keeps on growing? Like folks that are immunodeficient, because there was the HIV/AIDS crisis, which I think we've got like fixed mostly, right? Like it was a gigantic problem in the 1980s, '90s, '70s, right? But is it still a growing problem? Isn't this market currently served, or is it still drastically underserved and growing?

Yeah, the unfortunate truth is the number of recognized and diagnosed severe immunodeficiencies is growing over time. It's not decreasing. In fact, as of today, And this is according to some of the immunodeficiency patient foundations that we work with and we have strong partnerships with. If you look at some of their latest statistics, there's over 550 different recognized immunodeficiencies. Many of them involve antibodies, some of them involve T cells or other elements of the immune system. But the short answer is there's really no shortage of conditions that afflict these people and render them highly susceptible to infectious agents, even if let's say we're healthy and we're experiencing them all the time, you and I, we're not even noticing because we're fighting them off so effectively. We're not feeling any of the symptoms of those infections. But for these patients, that's not the case. They're more likely to have severe infections, for those infections to last a very long time, and for them to become so severe that the person may need hospitalization or specialty expensive medications. So that's the reality for patients with these conditions.

And it's not HIV/AIDS, it's like they are born with these, these deficiencies, right? Like, and why do you say it's a growing market? Like, can you point out to some specific cases or they're all pretty much quote unquote rare, rare diseases?

Yeah, good question. They're not all rare diseases. Some of them are. And we actually started with a rare disease called common variable immune deficiency. But the reason for that, especially because The Odyssey is this, you know, very famous movie in theaters now, there's the concept of the Trojan horse. So, CVID, or Common Variable Immune Deficiency, from a financial and regulatory perspective for a biotech company, is very interesting because it is a rare disease. So, it triggers certain incentives that a company like ours can obtain from the FDA with respect to potential expedited reviews when we get to those regulatory actions, as well as a— it's like a certificate called a priority review voucher, which has a significant market value. That biotechs can actually trade with each other. And only companies that are launching products for rare diseases can obtain this voucher. And so those can then be sold on the biotech market to companies that are seeking that type of voucher. And those can be very lucrative transactions. So those are some of the reasons to pursue a rare disease. But— and I know as a founder, you always hear people pitching like, this is a platform. Well, in this case, this is actually a platform because the same core technology of starting with milk, extracting the antibodies and then formulating that for patients, this can apply to multiple different disease types. It's not only for common variable immune deficiency. So that's why I said that's the Trojan horse that establishes a really clear go-to-market pathway. And then that, you know, that land and expand cliché that founders like to use— well, once that's approved, we know that there's all these other disease states that would benefit from, uh, similar technology. And therefore you're repurposing something you've already paid to develop, so you're amortizing and de-risking the early development steps that you've already invested in, which was your point about how costly will it be to stand up a new technology like this. So that's how you, you de-risk the venture and amortize the cost over a much, much longer time period.

Yeah, I saw allergy and asthma conference you've been at, so I mean, this can be applied to a bunch of things. Can it also be used in healthy patients for optimization purposes? Don't we risk weakening our immune system and making it like Lazier?

Oh, if you had a product like this?

Yeah, I mean, I would use it as a biohacker to not get sick like ever. And it's not about just get sick, it's like even in the process of having some of your immune system fighting something, it takes my energy away from work. Um, so could it be used like from an optimization perspective?

We have been approached about this a lot from the like the optimization and longevity, right? Yeah, exactly. So we get these inquiries a lot. So one way that we are— we have put a lot of homework into is exploring if this could lend itself to a supplement strategy, um, such as the nasal spray, such as, you know, oral droplets, something like that. Makes a lot of sense. We've done a lot of homework, and, um, you know, we're not ready to share exactly where we're going to take that direction, but we're very fortunate that my co-founder spent many years at the FDA as a regulatory policy fellow. And so these strategies of like like, could you launch it as a biologic? Could you launch it as a supplement? What's the sequence you need to do that? We've thought through a lot of that, and so we've built some really compelling strategies to do that.

And what's your very next, uh, priority? Is it fundraising? Is it starting to build your client pipeline? What is it?

It's really just two things. It's, uh, securing the financing, which we're working on, and we've made most of our progress in our current round already, but there is additional capital that we're seeking. And then really what that does is to go from flow number 1 to number 2. And number 2 is to position the company for clinical trials. So all the studies we've done so far have been in vitro, so cells and dishes, you know, cuvettes, tubes, things like that. We've done a large series of animal studies in both mice and rats to establish pharmacokinetics, establish efficacy in multiple different models. We've published studies, one in COVID-19, and the other one is set to be published any week now, you know, in a top-tier journal. And so we've established all of the preclinical datasets that are vital for any young biotech company. What you do when you hit a certain threshold of nonclinical studies is you wrap that into a package for presentation to the FDA so that you can position the company to open clinical trials. And that's what this financing is really about, to position the company to create product at clinical grade and then to deploy that into the clinic via clinical trials. So that's all of what's happening from now till the end of 2027.

I love it. Thank you, Viraj, for coming on. Where can people find out more about you?

So I'm on LinkedIn. I'm very easy to find. I'm very proud of our website as well. It's just www.lactiga.com. And, you know, this has been a great opportunity. I look forward to hearing from your fans.

Was Viraj and Charles for another