S2, E1: Mana.bio and programmable lipid nanoparticles with CEO Yogev Debbi and RNA expert Dr Barry Ticho

[00:00:03] Welcome to the Raising Biotech podcast.

[00:00:05] I'm your host, Surani Fernando and thanks for tuning in.

[00:00:08] This podcast has a mission of exploring biotech's raising impressive funds

[00:00:13] to develop ambitious medical breakthroughs.

[00:00:15] I speak with CEOs and founders to get origin stories, missions

[00:00:19] and future visions for the company.

[00:00:21] And I also talk with relevant medical and industry experts

[00:00:24] to get more context on the company's potential

[00:00:27] to really make a difference in healthcare.

[00:00:30] This episode is partnered with Mindgram.ai,

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[00:01:05] Now let's get back to the show.

[00:01:08] Today we're diving into Israeli lipid nanoparticle startup Manah Bio.

[00:01:14] It's a tech meets biotech story as the company is using AI and machine learning

[00:01:19] to develop novel and programmable lipid nanoparticle formulations

[00:01:24] that can deliver gene therapies too hard to reach organs.

[00:01:28] Something many gene therapy companies are struggling to do.

[00:01:32] The company announced an over-subscribed 19.5 million dollar seed financing in October 2023

[00:01:38] and is now partnering with gene therapy companies to realize their breakthrough vision.

[00:01:44] Joining me on the podcast is CEO Yorkev Debi

[00:01:47] to talk through the company's foundation, fundraising journey and future goals for Manah.

[00:01:53] This is also a very unique episode as Manah's official company launch announcement last year

[00:01:58] overlapped with the October 7th Hamas attacks.

[00:02:02] Yorkev gives us his first-hand account of what it was like to suddenly become a wartime CEO

[00:02:08] and how he navigated his team through some shaky beginnings.

[00:02:13] Also joining us is big-farmer veteran, RNA expert

[00:02:16] and chief medical officer of Stoic Therapeutics Barry Tico

[00:02:19] to give us his perspective of Manah's potential.

[00:02:23] I hope you enjoy the episode.

[00:02:25] Hi Yorkev, thanks for joining the podcast.

[00:02:27] Hi, thank you so much for taking time in this, Rani.

[00:02:31] So just to start us off, I always like to start off this podcast with this question.

[00:02:35] Can you explain the crux of Manah Bio and the problem that the company is trying to solve with its technology?

[00:02:41] Yeah, of course.

[00:02:42] So I think by that time, everybody knows that the next generation of therapeutic and vaccine is really nucleic acid-based,

[00:02:49] meaning RNA, CRISPR, DNA, etc.

[00:02:52] And if you ask the experts, the main challenge in unlocking this new therapy is really delivering,

[00:03:00] meaning how you take these molecules and put them into the human specific cell and specific tissue.

[00:03:06] So that's a challenging task.

[00:03:08] People are working from this task for thousands of years and with limited success.

[00:03:13] The main reason it takes a lot of time and money to really find a good solution for delivery

[00:03:20] is because the underlying logic of biology is not known to us.

[00:03:24] So we don't know why things work the way they are, and hence it takes a lot of time and money.

[00:03:30] So the thesis behind Manah is really to leverage the new approach of AI and machine learning

[00:03:35] in order to make sense of the data and by that to find novel solutions for delivery.

[00:03:43] So what exactly are lipid nanoparticles?

[00:03:47] Well, in brief, they're little fatty delivery shuttles encapsulating genetic material,

[00:03:52] and some of you may remember that they rose to fame during the pandemic

[00:03:55] for their performance in the award-winning mRNA vaccines.

[00:04:00] The lipid nanoparticle protected the mRNA strand from being destroyed within the body,

[00:04:05] carried it safely to cells to make that spike protein, at which point the lipid nanoparticle dissolved.

[00:04:11] Sounds simple, but the recipe to make these microscopic fatty shuttles was incredibly hard to perfect.

[00:04:18] In fact, it took over 30 years, and the pandemic was a major milestone and validator

[00:04:23] for these highly functional and nifty lipid nanoparticles.

[00:04:27] But even with this huge progress and milestone, currently lipid nanoparticles can only reach the liver.

[00:04:34] So they're now being used by companies developing gene therapies for liver diseases,

[00:04:38] but if they could reach other tissues in the body, this would open up a whole new world for gene therapies.

[00:04:44] So coming back to Manah.

[00:04:46] Manah is trying to create programmable lipid nanoparticles that can reach different tissues successfully,

[00:04:52] delivering whatever molecule it has inside mRNA, DNA, gene editing CRISPR to do its therapeutic magic.

[00:05:01] Sounds complex, definitely a tall order and bound to have challenges.

[00:05:05] But Manah's secret source is its own proprietary AI platform that is helping them crack the code

[00:05:11] or crack the recipe to get these lipid nanoparticles to the organ of choice.

[00:05:16] We'll come back to more of the science, technology and therapeutic potential later,

[00:05:20] but let's hear from Yorkev on what led him and his co-founders to start the company,

[00:05:25] which is particularly fascinating given he's more of a tech guy, not an original biopharma guy.

[00:05:31] So my background is actually computer science.

[00:05:34] After the graduating, I actually worked at Intel Corporation for many years

[00:05:39] in different software developing positions.

[00:05:42] And then I started my first biotech company back in 2011, which was software for gene editing.

[00:05:48] It was just when synthetic biology started.

[00:05:51] That company was called the Genome Compiler Corporation and less than five years after starting that company

[00:05:57] with other co-founders, the company was bought by Twist Biosciences in 2016.

[00:06:03] After that, Yorkev worked within Twist Biosciences for four years

[00:06:07] and saw it through its successful IPO in 2018.

[00:06:11] Then in 2020 he spent a short stint as VP of popular tech startup company Monday.com,

[00:06:17] but it was during COVID that Yorkev realized that his real passion was life sciences.

[00:06:23] And I wanted to do something impactful that will involve software.

[00:06:27] So at that time, my co-founder at Mana, Roy and myself, which we know each other for the past 20 years,

[00:06:34] we actually studied together.

[00:06:35] He got together with former co-founder of his previous company, Roy Nevo,

[00:06:39] who was also one of his classmates at university.

[00:06:42] And they decided that they wanted to start something new that would be impactful in the life sciences space

[00:06:47] but involved software because of their background.

[00:06:50] And so we went down for ideation phase where we discussed and we talked with many smart people

[00:06:56] and looked for the next challenge and really different areas.

[00:06:59] And then after a few months of ideation, we were lucky to meet two professors from the Technion.

[00:07:05] The Technion is kind of the MIT of Israel.

[00:07:07] So one of them, I wish there is a professor for chemical engineering

[00:07:11] and he is a graduate of Bob Langer's lab at MIT.

[00:07:15] Just a side note here for those not aware,

[00:07:17] Bob Langer is quite a renowned chemical engineer,

[00:07:20] most famous for being one of the founders of mRNA powerhouse Moderna,

[00:07:24] along with founding other biotechs which has essentially made him a billionaire himself.

[00:07:29] For Avi Shroder, that wasn't a bad mentor to be under.

[00:07:33] So anyway, Avi was working at the time with Israeli computer scientist and inventor, Kira Radinsky,

[00:07:39] who was a visiting professor at Technion and an AI and machine learning expert.

[00:07:44] So with the unique and curiously complementary backgrounds,

[00:07:48] Avi and Kira had this idea of using AI and machine learning

[00:07:53] to build a platform that would generate novel lipid nanoparticle formulations

[00:07:58] that can successfully deliver gene therapies to hard-to-reach organs.

[00:08:02] So that's how it all started and we met them literally by chance.

[00:08:08] That was like a total sudden deputy.

[00:08:10] So all of these chance meetings and ideations happened in 2021.

[00:08:14] After the co-founders did a tech transfer from Technion,

[00:08:18] the company's fundraising efforts was a little bit of an unorthodox journey.

[00:08:22] One of the interesting things that we did, Roy and I during the ideation phase

[00:08:27] was I call it reverse due diligence.

[00:08:29] Yorgev and Roy had already developed some relationships with investors

[00:08:33] from their previous journey as entrepreneurs

[00:08:35] and Yorgev said that they would often just casually pitch interesting ideas to these investors

[00:08:40] while obviously getting a lot of pushback and challenges on every idea.

[00:08:44] When we introduced this idea that, hey, there is a potential here

[00:08:49] to really unlock delivery of RNA using machine learning and AI,

[00:08:53] that was almost an immediate okay well in moment.

[00:08:58] So Manus first two investors were involved with Yorgev and Roy

[00:09:01] with their previous company and that's NFX and Lionbird

[00:09:05] and they financed Manus with a pre-seed financing of $5 million in 2021.

[00:09:10] Yorgev described this as a relatively easier journey to raising funds

[00:09:14] compared to the traditional slog of trying to find biotech investors.

[00:09:18] These investors knew the founders well and there was a mutual trust

[00:09:22] while the very clear objective was to get a team hired,

[00:09:26] develop the foundations of the technology

[00:09:28] and get some partner interest and excitement.

[00:09:31] So in the next 18 months, we build the team,

[00:09:35] build the lab and use the first money to really put the infrastructure in place

[00:09:40] meaning do the two main things in the company.

[00:09:43] One is generating data and the other one is really making sense of the data

[00:09:48] or really building the machine learning models that actually leverage the data

[00:09:52] to predict and to engineer novel molecules for delivery.

[00:09:58] So on the generating data side, we built a proprietary software tools

[00:10:02] that actually scraped the literature and take all the public information

[00:10:06] that was collected during dozens of years since this industry actually exists.

[00:10:11] We also started generating data in our own proprietary lab

[00:10:15] where we generate data on a weekly basis in a in a high throughput manner

[00:10:20] and using this data we're able to build models that allowed us

[00:10:24] to predict solutions and we showed nice in vivo data.

[00:10:28] And so this is on the on the on the actual scientific data.

[00:10:32] This data was protected by IP.

[00:10:35] So we we find that at that time it was two patents that we filed.

[00:10:40] And in parallel to that, we built relationship and started early discussions

[00:10:45] with potential partners that will actually leverage the business opportunity

[00:10:51] in the industry.

[00:10:52] So after 18 months using all this package and really hitting all the milestones

[00:10:57] that we put ourselves in the preceded round, we were able to raise additional round.

[00:11:03] Additional investors coming on board included Anderson Horowitz Bio and base for capital.

[00:11:09] So we call it the seed round, which was additional 14.5 million dollars.

[00:11:14] As Manor finalized its seed financing, there was set to officially launch

[00:11:18] the company on October 10th 2023 and present the company at an international conference.

[00:11:24] They had a press release and exclusive story planned for that day,

[00:11:28] but the company's launch coincided with one of the biggest terrorist attacks

[00:11:32] in Israel's history, the October 7th Hamas attacks,

[00:11:36] a horrifying event that has led to a full blown war, which is still very much ongoing.

[00:11:41] Now this podcast isn't a political podcast

[00:11:44] and we're focused on the story of the science and people behind it.

[00:11:48] But this unprecedented event has heavily impacted Manor's journey and mission

[00:11:53] and I asked Yorkev to take us through his first hand experience

[00:11:58] of handling this major company, Milestone, as a newly labeled wartime CEO.

[00:12:04] So the whole country was under some chaotic times

[00:12:08] and everyone literally was busy with dealing the situation.

[00:12:13] We weren't sure what the next few days gonna look like.

[00:12:16] In addition to the sudden attack, we got a rocket attack

[00:12:20] almost all of the country in the north, in the south,

[00:12:23] in the center in Tel Aviv area.

[00:12:25] So we ran to the shelter a few times today. It was really crazy.

[00:12:29] Crazy indeed, which seems like an understatement.

[00:12:32] So as everyone was in a state of unknown,

[00:12:35] Yorkev was dealing with his own conundrum

[00:12:37] of whether or not he should go ahead with the launch of the company.

[00:12:41] October 7th was Saturday.

[00:12:43] So I was about to fly the day after to the conference

[00:12:45] where I'm supposed to give an attack about the company for the first time.

[00:12:50] And we were like, okay, what should we do?

[00:12:54] Am I gonna fly out? I don't know.

[00:12:56] And then a couple of hours into the attack,

[00:12:59] and suddenly I got the notice that the flights are canceled.

[00:13:03] So that was an easy decision. I'm not flying.

[00:13:05] But then what should we do with the press release and everything?

[00:13:08] Every hour my mind changed.

[00:13:10] And I had three days and I remember that we had discussions

[00:13:13] whether what we should do because honestly,

[00:13:16] it felt almost inappropriate to come up with these news

[00:13:20] which are positive and exciting news for us as a company.

[00:13:23] But then it's like, almost like marketing activity

[00:13:27] in parallel to people fighting a war.

[00:13:29] Like that doesn't seem appropriate.

[00:13:31] And nobody had the answer

[00:13:33] because nobody obviously had this event before.

[00:13:36] So eventually my intuition was after considering all different aspects,

[00:13:42] I said, okay, we should actually go as planned with the release.

[00:13:46] Because eventually we wanna communicate that we keep pushing forward.

[00:13:53] I mean, it's not back to normal. It's not back to business.

[00:13:55] But we keep pushing forward. We don't give up.

[00:13:58] And I actually wasn't sure that this is the right decision.

[00:14:01] And I remember that the night before on the Monday night,

[00:14:04] my co-founder Roy called me and he said,

[00:14:07] Yorgev, are you sure we're gonna go out with this tomorrow?

[00:14:11] So I told him, you know what? I'm not sure.

[00:14:13] And eventually we decided like this is the decision.

[00:14:16] The decision is to move forward and to go out with the release.

[00:14:18] So we did that on the Tuesday.

[00:14:20] And I was really a tension, you know, what will the reaction be?

[00:14:24] And I was happy eventually that people were super positive about it.

[00:14:29] And they were really encouraged by that.

[00:14:32] And some people, many people actually, they actually thanked us.

[00:14:36] Like they thanked me and said, wow, these are great news in these dark times.

[00:14:39] Thank you for that.

[00:14:41] And so people...

[00:14:42] Like people in Israel?

[00:14:43] People in Israel, yeah, that was my main concern.

[00:14:46] Obviously people around the world were super positive

[00:14:49] because people that knew us, they were super positive about it

[00:14:53] and gave me dozens of notes around the world.

[00:14:59] They're really supportive.

[00:15:00] But yeah, people in Israel were really encouraged by that, which was great for us.

[00:15:04] But the announcement was just the first step in quite a topsy-turvy time

[00:15:08] for Manor's early days after its launch.

[00:15:11] They had to operate the company in a time of war.

[00:15:14] 25% of its workforce was called to reserve duties.

[00:15:18] Many employees were distressed and distracted by the war

[00:15:21] trying to help in ways they could

[00:15:23] while the daily rocket attacks meant the entire team had to work from home.

[00:15:28] Which is kind of complicated when many people needed to be in the lab.

[00:15:32] Manor had to make a lot of pivots with its business decisions during this time

[00:15:36] and was communicating on a daily basis to partners and investors

[00:15:41] that the company was very much still 100% committed

[00:15:45] to moving the project forward in every way possible.

[00:15:48] And then I think one important thing that happened was that

[00:15:52] people were really busy with volunteering

[00:15:54] and helping the actual physical war down in Gaza.

[00:15:59] Some mindsets in the country in the first few days or couple of weeks

[00:16:03] was that it's okay to give up work for helping the war, right?

[00:16:09] And if you think about it, it kind of makes sense.

[00:16:11] But then when I kind of thought about it, I decided, you know,

[00:16:14] the soldiers, the people that actually went to fight the war,

[00:16:18] that's like this is their job.

[00:16:20] But all the others, the workforce, okay, if you work in a company,

[00:16:24] then the real win is for you to move the economy forward.

[00:16:30] And if you're working, especially if you're working in science,

[00:16:33] working with overseas, working in innovation technologies,

[00:16:36] it's important for you to keep the business running,

[00:16:39] keep the technology innovation in Israel running

[00:16:41] because that's the real win.

[00:16:43] So I thought the thing, you know, this is important that you make the work here

[00:16:46] because we need to build the trust with our partners

[00:16:49] and this is for us the real impact.

[00:16:52] And so they got it and immediately everybody got to work with full motivation.

[00:16:57] So while Manor worked on getting its momentum back,

[00:17:00] the company still had to operate with five out of its 20 employees

[00:17:04] on the battlefield as army reserves.

[00:17:07] And to my surprise,

[00:17:09] Yoggav actually said that those employees were also trying to multitask on the battlefield,

[00:17:14] keeping up to speed on company affairs in their free time,

[00:17:18] dialing into Zoom calls and even coming into the office on vacation days.

[00:17:22] I think when you work with Israeli companies,

[00:17:25] you see that people really, really care about what they do.

[00:17:28] People are just juggling.

[00:17:29] On the day to day, you juggle between family and work

[00:17:33] and when you're in reserves duty,

[00:17:35] you juggle between reserve duty and family and work,

[00:17:38] which is it sounds crazy, but it's happened.

[00:17:42] I mean, yeah, they really tried to be involved,

[00:17:46] but it's really hard, you know, it's really hard

[00:17:48] because you can't be physical connected to the office.

[00:17:52] People made all the effort to from the minimum of a state connected

[00:17:58] and read the summaries,

[00:18:00] listen into the recordings of the internal meetings

[00:18:02] and make sure that they are up to speed.

[00:18:05] That was really some awkward situations

[00:18:08] of people taking calls from the actual from the field.

[00:18:11] And while the war continues and escalates on the broader front,

[00:18:15] Yorkev said that intense period of having 25% of the workforce

[00:18:19] being called to reserves duty lasted around three months.

[00:18:24] Each one has a different timeline,

[00:18:25] but more or less about three months of intense operation.

[00:18:30] And I say it's not really back to normal.

[00:18:33] It's not normal.

[00:18:34] Okay, we still have 133 people kept in captivity.

[00:18:40] So hostages, civilians again, most of them.

[00:18:44] So that's crazy.

[00:18:45] It's not normal.

[00:18:46] However, I say it's kind of stable for the past few months.

[00:18:48] So the past three months, things are stable,

[00:18:51] at least from professional or at least from the company perspective

[00:18:56] in terms of ability to push forward to have business

[00:19:01] to rely on suppliers locally and overseas,

[00:19:06] rely on infrastructure.

[00:19:08] So that things are operating really well in the past three months.

[00:19:12] Yeah. So stable under the circumstances.

[00:19:15] So we can still fly out or shipping cargoes.

[00:19:18] I mean, you don't have all the flexibility

[00:19:21] when you want to fly out travel,

[00:19:23] but you can fly like every day to everyone.

[00:19:27] So shifting from the chaos and sadness of a modern war,

[00:19:31] let's look at Manor's platform technology

[00:19:33] and its potential opportunity

[00:19:35] to make a significant impact in the biopharma world.

[00:19:38] This is Barry Tico.

[00:19:39] I am by training a pediatric cardiologist.

[00:19:43] I have PhD in biochemistry as well

[00:19:46] and was on staff at Harvard Medical School

[00:19:49] and Massachusetts General Hospital.

[00:19:51] Barry has a pretty extensive resume,

[00:19:53] so his medical and academic background stirred up

[00:19:56] a passion for translational medicine

[00:19:58] and he spent over 25 years in biopharma

[00:20:01] in companies like Merck, Biogen and Pfizer

[00:20:03] and has been more recently focused on RNA therapeutics

[00:20:07] spending a couple of years at Moderna.

[00:20:09] He co-founded Verve Therapeutics

[00:20:11] which is developing CRISPR-based gene editing therapies

[00:20:15] and currently holds the position of chief medical officer

[00:20:18] at Sturk Therapeutics,

[00:20:19] focusing on severe genetic diseases.

[00:20:22] Now given his background,

[00:20:23] he advises a lot of companies

[00:20:25] on cardiovascular diseases and RNA medicines

[00:20:28] and Manor is one of those companies.

[00:20:30] I asked him to really break down Manor's approach

[00:20:33] in developing programmable lipid nanoparticles

[00:20:36] and what makes this such a huge opportunity

[00:20:39] for the investors that got involved in the seed round?

[00:20:42] The potential for lipid nanoparticles is tremendous

[00:20:46] in this area.

[00:20:47] Multiple companies have highlighted

[00:20:51] that delivery of their technology

[00:20:55] is the biggest stumbling block that they have.

[00:20:58] For instance, you just talked to,

[00:21:00] to Alterna recently

[00:21:02] and they're using a lipid nanoparticle.

[00:21:04] They can only deliver to the liver right now

[00:21:06] and there are so many companies

[00:21:08] that have technology like that,

[00:21:10] TRNA, anti-sense RNA

[00:21:13] as well as mRNA

[00:21:16] that all could have tremendous use for other diseases

[00:21:20] but are being held back solely because

[00:21:23] they do not have a way of delivering to other tissues.

[00:21:27] And so what Manor is doing

[00:21:29] is addressing that specific need

[00:21:33] and taking it from the place

[00:21:37] where other companies have not been successful,

[00:21:40] taking it from a completely new approach

[00:21:43] and seeing whether that new approach

[00:21:45] can overcome some of the challenges

[00:21:48] that have prevented us from having lipid nanoparticles now

[00:21:51] that can go to almost any part of the body.

[00:21:53] He mentioned that Manor's approach

[00:21:55] of using machine learning NAI

[00:21:57] to screen the novel lipid nanoparticles

[00:22:00] separates them from the traditional approach

[00:22:02] giving them a unique edge.

[00:22:04] They are able to take learnings

[00:22:07] from many different other previous attempts

[00:22:11] at lipid nanoparticles

[00:22:13] and determine how to optimize

[00:22:16] the lipid nanoparticle design

[00:22:18] based on previous experience

[00:22:20] and that allows them to do

[00:22:23] an almost agnostic approach

[00:22:25] to design

[00:22:28] that optimizes

[00:22:30] the delivery for the type of tissue

[00:22:33] that is being targeted.

[00:22:35] Another key edge around what Manor's doing

[00:22:37] is related to intellectual property.

[00:22:40] There is a very complicated

[00:22:43] and dense intellectual property

[00:22:45] landscape for lipid nanoparticles

[00:22:48] and that has prevented some companies

[00:22:51] from developing novel lipid nanoparticles

[00:22:54] because of the concern

[00:22:56] about having freedom to operate.

[00:22:59] Simply put, all the different lipid nanoparticles out there

[00:23:02] are different concoctions of fat and fat-like substances.

[00:23:05] The outer shell is often a protective layer

[00:23:07] and the inner shell is often a combination of fatty substances

[00:23:11] like cholesterol, phospholipids

[00:23:13] and cationic or ionizable lipids.

[00:23:16] They design their lipid nanoparticles

[00:23:19] specifically to allow for potential

[00:23:23] filing of new patents

[00:23:25] that avoid conflict with other patents

[00:23:27] and so that makes these new lipid nanoparticles

[00:23:31] more attractive

[00:23:33] based on the fact that having patents

[00:23:36] for one's technology is a very important part of a successful company.

[00:23:40] Barry and I talked about what Manor has been able to show

[00:23:43] so far in its early animal models

[00:23:45] and what organs make sense for Manor to target first.

[00:23:49] Manor has already demonstrated

[00:23:51] the ability to deliver lipid nanoparticles

[00:23:54] selectively to belong, to explain

[00:23:57] and are working now on delivery to the brain as well

[00:24:02] as to T-cells and other blood-based cells.

[00:24:06] So these are all very important areas of need.

[00:24:11] So they have done quite a bit of work in mouse models.

[00:24:15] They have some experience in non-human primate as well

[00:24:18] and they are now developing partnerships

[00:24:21] with multiple other companies

[00:24:23] who have specific tissues

[00:24:26] or specific characteristics of the lipid nanoparticles

[00:24:30] that they would like Manor to develop.

[00:24:32] So they are at the stage right now

[00:24:34] where they've proven that they can develop

[00:24:38] these new lipid nanoparticles

[00:24:40] that have the desired targeting

[00:24:43] as well as the freedom to operate.

[00:24:48] And so now they're really going back

[00:24:51] and taking the recipes that the partners are developing

[00:24:54] or the recipes that the partners give them

[00:24:57] and designing lipid nanoparticles

[00:25:00] that fit those requirements.

[00:25:02] Talking about the potential diseases

[00:25:03] that could be theoretically

[00:25:05] tackled with these optimized lipid nanoparticles,

[00:25:08] Barry said that in the oncology field,

[00:25:10] lipid nanoparticles could perhaps be a vehicle

[00:25:13] to find T-cells to treat them directly in the body

[00:25:17] so that they can then fight blood tumors,

[00:25:20] something that right now, for example, with CAR-T therapies,

[00:25:24] happens in a very long, taxing and expensive process

[00:25:27] where cells are removed from the body, treated

[00:25:30] and then infused back into the patient.

[00:25:32] It's effective but could be a lot simpler

[00:25:35] if lipid nanoparticles were involved.

[00:25:37] Essentially off the shelf, easy to administer treatment

[00:25:41] that can accomplish the same thing

[00:25:43] as what's being done with CAR-T cells.

[00:25:45] But it also, as I said, has potential impact

[00:25:48] beyond cancer treatments.

[00:25:50] There are already companies working on in vivo ways

[00:25:53] to manipulate T-cells, for instance,

[00:25:55] to address diseases like heart failure

[00:25:57] or other fibrotic diseases where those cells can go

[00:26:01] and remove cells that are causing fibrosis

[00:26:04] or causing scarring and allow those tissues

[00:26:06] to heal normally or to rejuvenate themselves

[00:26:09] and have more of a normal cell base

[00:26:12] rather than a scar-based cell.

[00:26:15] Down the road, the treatments in the lung

[00:26:17] for cystic fibrosis where one could make changes

[00:26:21] in the DNA of the pneumocytes in the lung

[00:26:24] and change the CFTR gene back to its normal wild type

[00:26:29] or normal genetic structure.

[00:26:30] And that would be a potential treatment

[00:26:32] for cystic fibrosis.

[00:26:34] There are treatments for brain diseases.

[00:26:36] This is a little bit further down the road.

[00:26:37] But ultimately there would be quite a few brain diseases.

[00:26:40] There would be quite amenable and needed

[00:26:42] for gene editing to treat those diseases.

[00:26:45] So it seems like in an ideal situation,

[00:26:47] all going well, skies the limit for Manor

[00:26:50] with the amount of diseases its platform

[00:26:52] could offer value to.

[00:26:54] But while there is a lot of theoretical potential,

[00:26:57] these haven't been tested in humans yet.

[00:26:59] And there are always unknowns

[00:27:01] when it comes to first-in-man trials.

[00:27:03] But Manor does hold a unique advantage,

[00:27:06] a major de-risking event

[00:27:08] which was a little thing called the pandemic.

[00:27:12] The utility of lipid nanoparticles

[00:27:14] has been clearly stated

[00:27:17] through the development and availability

[00:27:19] of the COVID vaccine,

[00:27:21] which uses lipid nanoparticles to deliver messenger RNA.

[00:27:25] And that has obviously built up both the capacity

[00:27:29] to manufacture lipid nanoparticles,

[00:27:32] which is an important need

[00:27:34] as well as identify the utility

[00:27:37] as well as the safety of delivery using this method.

[00:27:41] In addition to the COVID vaccines,

[00:27:43] all the other treatments using lipid nanoparticles

[00:27:46] that target the liver

[00:27:47] also de-risk Manor's end of the bargain.

[00:27:50] That's where safety and utilities involved.

[00:27:52] But that said, Manor has a pretty steep road ahead

[00:27:55] and a lot to think about

[00:27:56] to get its various lipid nanoparticle formulations

[00:27:59] optimized for combined success

[00:28:02] with its partner's payload.

[00:28:04] The challenge of delivery is really huge

[00:28:06] in terms of you have to build

[00:28:08] these highly customized solutions

[00:28:12] for the specific payloads,

[00:28:14] for the specific cell type,

[00:28:16] for the administration routes,

[00:28:17] for the application,

[00:28:18] whether it's the vaccine or gene therapy, etc.

[00:28:20] So people today talk about

[00:28:23] targeting those specific cell type,

[00:28:25] optimizing for safety or toxicity,

[00:28:27] optimizing for stability.

[00:28:29] So how much time the particle is stable

[00:28:31] outside the body and inside the body?

[00:28:34] And many different things.

[00:28:35] There are also things like

[00:28:37] manufacturability and cost effectiveness

[00:28:40] and the protocol itself.

[00:28:41] So there are many, many things

[00:28:42] that can be optimized and changed

[00:28:44] using this approach of data generation

[00:28:47] and machine learning models.

[00:28:48] So in order to have a platform

[00:28:49] which you can efficiently engineer solutions

[00:28:53] for these highly tailored tasks,

[00:28:56] you really need the powerful platform.

[00:28:58] And this is what we're focusing on.

[00:28:59] This is why I'm looking to leverage

[00:29:02] the platform technology through partners

[00:29:06] and to achieve preclinical

[00:29:08] and advanced preclinical and clinical data

[00:29:10] with partners.

[00:29:15] We're living in some pretty unique

[00:29:17] and advanced times now

[00:29:18] where tech guys are starting biotechs.

[00:29:21] And while 10 years ago,

[00:29:22] some veterans in the industry

[00:29:24] might have been skeptical

[00:29:25] about this type of founder profile,

[00:29:27] Barry believes they have a unique advantage.

[00:29:30] Yeah, I think their background

[00:29:31] is a huge advantage

[00:29:33] because it allows them to develop

[00:29:37] the algorithms

[00:29:39] and also come with a different perspective,

[00:29:43] a different approach

[00:29:44] to how lipid nanoparticles could be designed.

[00:29:47] So instead of coming from the lipid side

[00:29:51] or the chemistry side,

[00:29:53] their view is more on the design side.

[00:29:57] Barry added that down the road,

[00:29:58] Manor will also be in a good place

[00:30:00] to design the robots

[00:30:01] and test them more along the tech way of testing

[00:30:05] rather than some past methods

[00:30:06] within the industry,

[00:30:08] especially on how to identify sources of data

[00:30:11] for new lipid nanoparticle designs,

[00:30:13] but also testing those new designs

[00:30:15] in a more predictive manner

[00:30:17] to optimize the next versions.

[00:30:24] At this stage,

[00:30:25] Yoga of Sale Manor has three things

[00:30:27] it wants to accomplish.

[00:30:28] One is to validate more delivery assets

[00:30:30] in more advanced preclinical studies

[00:30:32] and prepare them for partnerships.

[00:30:34] The second is to unlock more tissues

[00:30:36] in the body

[00:30:37] that it can deliver its novel lipid nanoparticles to.

[00:30:40] And the third is to mature business discussions

[00:30:42] and early partnerships

[00:30:44] into more meaningful collaborations

[00:30:46] that realize the potential of Manor's technology

[00:30:49] with a clear path to market.

[00:30:52] And then, you know, what we're looking to achieve

[00:30:55] is some non-dilutive cash

[00:30:56] plus validation to our platform.

[00:30:59] And then we're in a position

[00:31:00] where we actually leverage the platform

[00:31:03] and build our own pipeline.

[00:31:04] I think this is down the road.

[00:31:06] This is the vision for the company

[00:31:07] because we'll be able to do that.

[00:31:09] We'll probably be able to build our own pipeline

[00:31:12] by in licensing payload

[00:31:14] and then once for the preclinical and the clinical trials.

[00:31:19] So already with aspirations to develop its own pipeline

[00:31:22] and its longer term plan,

[00:31:23] I asked Yoggyev where he saw the company

[00:31:26] in five to 10 years.

[00:31:27] Having made an exit before with his first startup

[00:31:29] I was curious to know

[00:31:30] if this was a gain on his radar

[00:31:32] or whether the team was more focused

[00:31:34] to build the company

[00:31:35] into a bigger lipid nanoparticle based therapeutics company.

[00:31:39] Perhaps one day in the distant future going public.

[00:31:42] So, you know, people ask me

[00:31:45] do you want to sell the company at some point?

[00:31:48] And I'm like, well, actually,

[00:31:51] you know, when we started MANA

[00:31:53] we started for something impactful

[00:31:54] in a meaningful field

[00:31:56] which will impact people

[00:31:58] and leverage the technologies that we know of.

[00:32:00] So if we sell MANA,

[00:32:01] we need to start MANA again.

[00:32:02] So we're not really looking to sell MANA

[00:32:05] in terms of private versus public.

[00:32:08] I mean, going public is just a fundraising event.

[00:32:11] So this is not the goal by itself.

[00:32:14] It's still too early to talk about it.

[00:32:16] But our vision is really to unlock the potential of RNA based therapeutic

[00:32:22] or nucleic acid based therapeutic.

[00:32:24] And this is something that we will do

[00:32:26] with the best use of our resources

[00:32:28] talent, money, et cetera.

[00:32:30] So for now, it makes sense to have your two collaborations

[00:32:33] later on with money that we get in

[00:32:35] we'll be able to even sponsor these programs.

[00:32:39] We're here for the long haul.

[00:32:40] The real purpose for us is to make an impact

[00:32:43] the best way we could

[00:32:45] and the most efficient one

[00:32:47] that will be a good alignment between all our team.

[00:32:52] Well, that's it for another episode of raising biotech

[00:32:55] a lot going on in this episode

[00:32:56] and given the unique circumstances

[00:32:59] Yoggav especially wanted to thank his MANA team

[00:33:01] investors, partners and service providers

[00:33:03] for all their hard work and support

[00:33:06] during the company's complicated beginnings.

[00:33:09] Thanks to Yoggav Debi and Barry Tico

[00:33:11] for joining the podcast

[00:33:12] and thanks to you all for tuning in.

[00:33:14] Remember to show your support for these podcasts

[00:33:17] please subscribe wherever you listen

[00:33:19] and leave a review on Apple or Spotify.

[00:33:21] But for now, I'm Serani Fernando

[00:33:23] and stay tuned for the next episode of raising biotech.