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Combating The Silent Pandemic | Dr. Anand Anandkumar @ Bugworks Research Inc.
160 Plays3 years ago
In this edition of Founder Thesis, Akshay Datt talks with Dr. Anand Anandkumar, CEO and MD of Bugworks Research Inc., a remarkable drug discovery company focused on developing novel broad-spectrum antibiotics and immunotherapies that stand to transform the healthcare ecosystem worldwide.
A veteran in the semiconductor industry with almost two decades of experience, Dr. Anandkumar wears many hats. To mention a few, he is the Vice President of the India Biotech Association & one of the founding members of the India Electronics and Semiconductor Association (IESA).
In 2005, he founded Cellworks which has significantly increased the success rate of cancer treatments by customizing therapy choices. An offshoot of Cellworks, Bugworks originated from the deep resolve to eradicate secondary bacterial infections, a major public health threat in terms of mortality.
Tune in to this episode to hear Dr. Anandkumar speak about how Bugworks has taken a unique path in drug discovery as it attempts to fight the war against rising antibacterial resistance.
What you must not miss!
- Current drug development challenges
- Monetizing drug combination therapies
- AMR and superbugs
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Transcript
Introduction and Zencastr Promotion
00:00:00
Speaker
Before we start today's episode, I want to give a quick shoutout to Zencaster, which is a podcaster's best friend. Trust me when I tell you this, Zencaster is like a Shopify for podcasters. It's all you need to get up and running as a podcaster. And the best thing about Zencaster is that you get so much stuff for free.
00:00:18
Speaker
If you are planning to check out the platform, then please show your support for the founder thesis podcast by using this link zen.ai founder thesis. That's zen.ai founder thesis.
00:00:32
Speaker
Hi everyone.
Meet Anand Kumar and Bugworks Research
00:00:33
Speaker
Good morning. My name is Anand Kumar. I'm a co-founder and CEO of Bugworks Research, a company based out of Bangalore, the US and Adelaide, Australia, working on next generation antibiotics. It's good to meet all of you.
00:00:56
Speaker
We've all
Why is Silicon Valley called Silicon Valley?
00:00:57
Speaker
heard of the phrase Silicon Valley. But did you know that the word Silicon in it refers to microchips that are made of silicon? And in a way, chip design remains one of the most elite high-tech chop profiles still did. You can't be a chip designer without being an intellectual giant.
Anand Kumar's Journey from Engineering to Health Tech
00:01:15
Speaker
Today our guest is one such intellectual giant, a Chennai boy who went to the US for higher education and ended up running global chip design companies in the US and then in India. Anand Anand Kumar is the son of a renowned doctor who ended up choosing engineering instead of medical as a way to make his own mark. But fate brought life full circle for him as he ended up getting into the field of medicine as an entrepreneur after a personal medical emergency made him question his priorities.
00:01:43
Speaker
He ended up founding not one, but two health tech companies, each of which is pursuing deeply complicated problems with the potential for impact at scale. Here's Anand telling Akshay Dutt about the journey of building his two startups, Cellworks, which is focused on cancer therapy and Bugworks, which is working to protect us from a bacterial pandemic.
00:02:03
Speaker
Very
Founding Cellworks: From Semiconductors to Cancer Therapy
00:02:04
Speaker
tough journey, because you're doing so well. The semiconductor industry is booming. I was one of the co-founders of the Indian Semiconductor Association. So that's starting to happen. All these companies are coming, Intel, Broadcom, Qualcomm, all these top chip design companies. They are our customers that we are serving.
00:02:22
Speaker
And then I got together with a bunch of guys from the Bay Area who are my neighbors in Bangalore and we decided to put this company together, Cellworks. Cellworks is still running a company and actually we thought we can use mathematical modeling to simulate biology. So that's the bleed over from engineering, physics, and mathematics modeling to doing chips.
00:02:42
Speaker
to saying, can I use the same thing to study biology? That's how I got into this space. It is very tough. I think my wife supported me the most because she realized I was going to give up a huge paying job for pretty much on nothing. My kids were really scared because they saw dad moving from five-star hotels to Cafe Coffee Day for my meetings or to Darshini for things. And even my parents were very upset that I was doing this shift. But I tell you what,
00:03:10
Speaker
When you make this shift for the right reason, you make that shift count. I told myself, let's do something in health care. Let's use all of this mathematics and engineering to create something in India that can help the world in cancer therapeutics, in personalized cancer therapeutics. And when you have such an overarching goal that you want to do something to humanity, all these other things are just minor distractions.
00:03:38
Speaker
They don't come into the main play because you pretty much realize that you have such a big mission. And early investors believed in that madness, in that energy they saw in the founding team to say, oh wow, you guys are going to use chip design techniques to strengthen cancer biology. What are you smoking?
00:04:02
Speaker
But then the things that this bunch of guys is trying to do and a bunch of scientists and engineers are trying to do something good for humanity. And we can't let those people down, right? So it's like you have to satiate the needs of all your stakeholders. So it wasn't an easy move over, but anybody who wants to do a startup with an overarching goal of giving back to society, either through medicine or through education or through agriculture or through environment,
00:04:31
Speaker
It is that overarching purpose that drives and then everything else falls on the wayside. Okay.
Cellworks' Innovative Approach to Cancer Treatment
00:04:38
Speaker
So I want to like go into the weeds. What was the traditional cancer therapies around which you were not satisfied with and wanted to build something better? What was that better thing that you built in cancer therapies as compared to traditional approaches?
00:04:56
Speaker
As we are learning now, cancer is a disease that is very personalised. Every patient's cancer is so different. That is why cancer is a booming industry because the variation, it's heterologous, it's not homologous. And we started seeing in late 2007-8 that cancer therapy
00:05:17
Speaker
Outcomes were very poor, 5%, 6%, 8%, 10%, right? Whether it's cancer or prostate or liver, some like pancreatic outcomes are even worse. The fundamental reason why the outcome is not good is because each person's cancer is defined by a signature that's different from person to person. And we said, wait a minute, what if I could somehow come up with a mathematical expression to model the cancer biology?
00:05:44
Speaker
and on computer be able to customize every patient. Therefore,
00:05:50
Speaker
The therapy used by the oncologist for her patients, for her or his patients, can potentially be very bespoke, can be very customized. It's called directed therapy or personalized therapy. That is the change that companies, not just us, there are several other companies that are trying to do it, but we were the battle of those early companies that uses systems biology to be able to bring genomic signature
00:06:15
Speaker
into cancer therapy so there can be customization. And we are still working 14 years into starting the company. We are still curating models, still running clinical trials in the United States to prove that prediction works. That's the journey of science companies is 15 to 20 years. It's never done deal. I wish we could say we are done and dusted, but still work in progress because so much new gene information
00:06:39
Speaker
Proteome protein information are coming in and we have to harness all of that information build these models. Work with oncologists who say wow your prediction was better than their their analysis on the patient. So that's that's where that's what we are coming into and still works is if you do a Google search and sell what should see we have more than 250 papers.
00:07:02
Speaker
And we have pretty much revolutionized the use of systems biology to customize treatment for heart to treat cancers. But we are not a drug discovery company. We are more a platform company that aids the oncologist in her selection of drugs to solve her patient's problem. OK. So kind of like recapping what I understand,
00:07:27
Speaker
Cancer treatment is radiotherapy, chemotherapy, a mix of these. As far as I know, my grandmother had breast cancer when I was just a kid. So I'm talking of 20 years back what I came to know.
00:07:43
Speaker
This combination of radiotherapy, chemotherapy needs to be personalized to the patient. It cannot be a one size fits all approach. And so what Cellworks did was it looked at certain data points about a patient to recommend the optimum mix of treatments.
00:08:05
Speaker
You almost got it right. So it's not just radiotherapy, chemotherapy. There are lots of molecules as well, medicines, molecular target therapies that are targeting particular targets. Chemotherapy is like a nuclear weapon, right? It goes in and takes out
00:08:20
Speaker
The cancer takes out many things along with it, which is why people become so sick, lose their hair, lose weight and everything because it takes anything that is fast dividing cells, right? Monically targeted therapies have less side effects but more expensive and they're targeting particular targets. We figured by bringing this massive genomic information in, when you do a biopsy of a patient, you get the genomic signature.
00:08:45
Speaker
Can we use the genomic signature to make the right predictions? This is before artificial intelligence and machine learning. So we had to actually stitch the Google traffic map of cancer using the biochemistry. So we took a whole bunch of biochemists and mathematicians and computer scientists and combined them together in cell works to stitch the Google traffic map of cancer, the actual biochemical pathways. And then you customize those pathways using the genetic biopsy data.
00:09:15
Speaker
So your red map is the same, but on some day you wake up and say, these two roads are closed. What happens to the traffic pattern? Some other day, three new roads are open. What happens to the traffic map? It's like that. Basic traffic maps are the same, but you customize the patient data and therefore have an ability to study the cancer in new ways that were never done before. So you almost got it.
00:09:40
Speaker
Okay, so what is this biological pathway that a cancer takes, which you just referred to, that you were able to map out? What does that mean, biological pathway? Sure. So whatever biochemistry, cancer pathways, cancer biology has been mapped out.
00:09:59
Speaker
We didn't invent it. It's scientists over the last 30 to 40 years have been studying and publishing papers that says this breast cancer, there are 40, 50 pathways inside the body, biochemical pathways that come together, something went wrong and it created a cancer. We took all of this published data out of proteomics, genomics, metabolomics, anything with omics study,
00:10:27
Speaker
and created the mathematical platform that could stitch these traffic maps. So, when I say pathway, these are the traffic maps. So, if you open up a single cell or you open up a cancer cell, there are many other pathways that are coming together.
00:10:42
Speaker
to create a particular end effect. So a pathway is like chain of chemical reactions inside the body. Exactly. It's biological pathways. And if you look at it, it's like opening up a complicated traffic map of a massive city like Los Angeles.
00:11:01
Speaker
And every morning you wake up in LA, somebody shows a huge map showing hundreds and thousands and thousands of small streets with traffic maps and live traffic data. That is the traffic map. So you have the biochemistry of the pathways and then you put the customized thing and the pathway network changes from patient A to B to C. So it's phenomenal.
00:11:27
Speaker
Like a pathway will show you how that cancer occurred and also how it is going to spread. How it is going to spread and a pathway basically is how normally things need to work. And then when you block something in that pathway, something else happens. The pathway study also tells you why a particular drug is not working for the patient.
00:11:48
Speaker
So if you have a pathway that needs to be like this and then there's a side street that comes off, then you know that the traffic can take two routes out. Good studies. And then you can figure out that even once you put your genetic signature on it, the genetic signature is like saying, block off this road, open this road.
00:12:10
Speaker
So your roads are slightly different than my roads. We are in the same city, but the roads that you are taking are slightly different than the roads I am taking. Therefore, how a drug works for patient B is different for how it works for patient A. It is studying the interplay of genetic markers and all of these cancer pathways. That study is impossible to do in a laboratory because of hundreds and thousands of pathways.
00:12:40
Speaker
but it's fantastic to do computation. So we are one of the first people that did it with cellworks. Got it, got it. Okay. And how many data points of the patient do you input into the model for it to throw out? Like I said, it's been 14 years in the making, on an average 100 people per year. So it can tell you 5,500 man years.
00:13:02
Speaker
of curation work is still going on. Hundreds and thousands of cancer biology papers are the inputs into this platform. And it's tens of thousands of data points. Tens of thousands of data points. It's so complex. And we're still not where we need to be. Ultimately, we won't go to a thing that cancer patient walks into an oncologist's office. Oncologists say, show me a biopsy data. You have a cancer. You take the biopsy data.
00:13:31
Speaker
just cut and paste that biopsy data into a network. The network runs a simulation in five minutes while the patient is waiting and says, for this patient with prostate cancer, for this type of prostate cancer, with this type of genetic background, don't use standard of care, use drug B. The ecologist clicks on drug B to say, why drug B? I never thought drug B would work. And then we open up a traffic map that says, if you use drug B, it can come in like this and clean up the traffic.
00:14:00
Speaker
If you use drug A, it'll come and get stuck here. It's got a pothole. It's not going to get through that road. It's got a pothole. Drug A is going to get through it. And then there are a couple of these days go try drug A. That is the society we want to get in. Very bespoke. No other disease offers this kind of customization because no other disease is so much dependent upon our genetic markers.
00:14:26
Speaker
So for giving this recommendation, you would need like the patient's genome. What does that mean? Typically, biopsy. When a patient has a cancer, the doctor does a biopsy to study the nature of the tumor, to know which kind of cancer, what stage of cancer you are in, whether it's fast spreading, what stage it is, et cetera, before they come up with the right medicine for that. All we need is that genomic sequence.
00:14:55
Speaker
that come from the biopsy. Of the cancer or of the patient? Of the tumor. And do you also need like the patient's DNA and stuff like that as part of the? We get it anyway as part of when you're doing the biopsy and you get the whole sequencing. There's enough data coming from the sequencing to run platforms like ours. Because everything that matters to this cancer is captured in the signature that comes from biopsy.
00:15:23
Speaker
And when you started, this was like pre-machine learning era. So you would have probably needed to hard code algorithms instead of just feeding it tons of data and letting it predict on its own.
00:15:35
Speaker
Very smart question, very smart question, yes. And remember folks like me who came to the 80s and 90s, we did machine learning and artificial intelligence in the 80s and 90s. It's just that we didn't have the horsepower to execute many of the neural networks and wavelet transforms and all the good stuff that we studied. Now we have it. So with cellworks, we struggled. We had to build some own hardware, then we moved to GPUs. And now a lot of cellworks' work, not a lot, but a significant minority of cellworks' work
00:16:04
Speaker
is moving to artificial intelligence and machine learning. We haven't seen AI perform anywhere close to actual hardcore biochemistry because that's the full pathways.
00:16:15
Speaker
It's the actual pathways that are sending signals here and there and cross-poupling and all this stuff. We haven't seen artificial intelligence perform anywhere close to that. You know, the way technology is moving, we will be proven wrong. Yeah, yeah, yeah. And so, like, how did you get this off the ground? Because this needs a lot of domain experts and it needs money to pay their salaries. How did you get it off from an idea to an execution?
00:16:45
Speaker
Yeah, very fortunate that our co-founders, three were my neighbors here and one was sitting in the Bay Area. So we got together. All of us had come from Chick Design background. And one of the co-founders had finished a postdoc from Stanford, really, really bright. So we started creating that first traffic map right from there. A lot of the money initially came from the founders.
00:17:09
Speaker
And then people started believing, say, hey, this looks like a dream that's worth betting on. And we started taking money from angel investors. The first two rounds were from angel investors. When did you do those first two rounds? Like from a timeline? 2007-2008 is when we did the angel rounds. And we're hoping to give them a payout at least now. This year or next year has taken such a long time.
00:17:35
Speaker
But
Funding and Early Commercialization of Cellworks
00:17:36
Speaker
many of them put money in because they have believed that we are trying to revolutionize cancer treatment and make better outcomes. Why are we doing this? So that the outcome rate can go from X to 2X or at least X plus 50%, right, or whatever. So initial money came only from angel investors in the Bay Area and Bangalore. And then Artiman venture capital out of the Bay Area, the first official investors in us in 2008, I believe.
00:18:04
Speaker
And then Sequoia, who was one of the top investors in the Bay Area, also became an investor in our company. How much did you raise? To date, I believe in Cellworks. Because remember, my current story is Bugworks, not Cellworks. But in Cellworks, to date, we have probably raised, I would think, about $30 million.
00:18:28
Speaker
Hmm. Okay. How much like in those early rounds, like Sequoia and Artiman, what was? Sequoia, Artiman is the majority holder of the company. So probably through Angel Investments, we would have raised 4 million and the remaining 25 plus million has come between Artiman, Sequoia and a few other companies. So I would say between Artiman and Sequoia itself would be close to 20 million.
00:18:56
Speaker
Okay, okay. And when did you start commercializing it, like cellworks? Has it got least commercialization stage? It's quasi-commercialized because you have to run so many clinical trials and these takes years and years and years. But the early commercialization, I would say, started in 22, 2017, 2018. But we started selling platform services. That means somebody pays
00:19:23
Speaker
It's like a software, like a solution, like a SaaS. I have a patient. I have the biopsy information. Can I run your platform? Can I put this biopsy information in this platform and run it? So it started as a platform services. And now we have moved to where we're working with pharmaceutical companies.
00:19:44
Speaker
that are using this platform to figure out which patient population suits their drug the best. Because they're spending hundreds and hundreds and hundreds of millions of dollars doing clinical trials. But clinical trials only works on a small subset of patients, correct, in cancer particularly, that have the correct match of genetic markers that match the treatment. The rest genomes, the rest fails.
00:20:10
Speaker
So what if we can work with these guys to identify very early which is the patient population to go after? Instead of spending $400 million and covering 500 patients, can I spend a fraction and go after just 100 patients with a higher probability of success? It's never guaranteed, but a higher probability of success. So we're working with pharma companies that pay us services dollars.
00:20:34
Speaker
to help reduce the burden of clinical transaction. So that's cellwords.
00:21:04
Speaker
Okay. And what is the revenue split between these two lines? Like you have this one line of clinical trial and the second line of platform. It's like 70-30, 70s platform and 30s towards this pharma, but very quickly I think it's going to become Ulta.
00:21:25
Speaker
to where there would be more traction coming out of pharma. Fair to say that at steady state, we will have three revenue lines. One revenue line is a platform services used by oncologists to customize trip.
00:21:38
Speaker
Two is pharmaceutical companies using this platform to reduce clinical trial costs, better outcomes for patients. And three is, cell work also does combination drugs discovery. That means taking existing drugs and saying for lung cancer, I can mix these two drugs and get a much better outcome. Existing drugs, not novel drugs, existing drugs. So I think it will split across these three. But right now, we are trying to move towards a 50-50 platform and pharma.
00:22:08
Speaker
How will the combination business be monetized? Like you discover a combination of drugs that works? Very, very smart question. In countries like India, it's very hard to monetize with the two existing drugs and put them together. But in the US, Europe, et cetera, something called method of use. If you figured out that I could take a sugar drug and a mental illness drug, a psychiatric drug, but I come down with them and they seem to do something for lung cancer. That's totally non-obvious.
00:22:39
Speaker
You can monetize it. Those countries are willing to pay as insurance companies like to pay for such drugs. You can't make big money like a novel molecule because these are generic drugs. But there is still a business to be made, not in India in that bond.
00:22:55
Speaker
like an insurance company would pay to acquire this information and spread it to their hospital networks. Exactly. So instead of spending $100,000 on a novel molecule that has a 20% probability it will help your patient is spending $100,000.
00:23:15
Speaker
even if it's $20,000 for a generic product, which has improved the chance of success, and for that you need to show proof, obviously, clinical proof. You know, insurance companies, it's very interesting that you asked a question, very brilliant observation. Our latest funder in cell works is an insurance company, United Healthcare, because they're spending billions, tens of billions of dollars on on-court treatments that are so expensive with very poor outcomes.
00:23:42
Speaker
What if they can improve those outcomes by even 20%? That will save them 10 billion. So our insurance companies have picked up platforms to reduce burnout for them. So that if they're putting $100, they want a good chance that $100 will work for that patient.
00:24:03
Speaker
Got it. I would have thought the platform for oncologists would be the biggest because that sounds mass market. There are maybe hundreds of thousands of oncologists all over the world.
00:24:14
Speaker
slow to adopt because they wanted to do plenty and plenty of clinical trials and in unlike infection and other areas in oncology each tumor has got sub segments so that clinical trial space is massive and complicated. So because oncologists want to make sure that this goes to FDA approval because you know hey it's all driven by legal frameworks in those countries right and but they are early adopters.
00:24:42
Speaker
Indian oncologists will adopt it once US oncologists adopt it. And US oncologists want to make sure that when they say, I trust this platform, it's as bulletproof as possible because they're putting their name on the line. So it's going through all of that massive clinical validation in the top institutions of the world. Right now it's being used.
00:25:06
Speaker
For an oncologist, it doesn't affect his bottom line as much as it affects for a pharma company. Therefore, those are like first of all terms. One would imagine, or an insurance company in the West that pays $100,000 per patient per year. Huge money, right? Got it. Okay. So tell me the journey from, you know, like, like what made you want to move on and start Bugworks?
The Birth of Bugworks: Tackling Bacterial Pandemics
00:25:33
Speaker
Right. So I'm still associated with Cellworks. I'm a shareholder and I'm on the board in India.
00:25:38
Speaker
Back in 2013 and 2012, while I was in cell work, started looking at infection. And I was looking about a different type of pandemic. Not a viral pandemic, but bacterial pandemic. Started seeing that too many people were dying because they go to hospital for a surgery and then pick up infection in the ICU. And even you would have heard of it saying, hey, everything went well, man, but they picked up infection. Oh my God, I'm mistaking weeks to clear or they pass away.
00:26:06
Speaker
seeing that lots of people in countries like India are dying every year, going into hospitals. Babies are dying when they are born in less than 21 days because the baby is born in a dirty hospital. She picks up the bug and she doesn't have enough of her immune system to fight the bug. Right, Akshay?
00:26:29
Speaker
I kept looking at it. And I convinced Cellworks that we should look at tuberculosis. Hey, can we use the same mathematical model to simulate DBE? Like with simulating human cancer. Obviously, Cellworks said you're mad. There is no money in TB. It's a poor man's disease. Plus, we are a cancer company. What are you talking about? So I said, no, let's do it. So I started collaborating with AstraZeneca, which is one of the famous pharmaceutical companies, AstraZeneca.
00:26:58
Speaker
who had a presence in Bangalore. This is in 2010, 2011, 2013. And we came together. And you won't believe it. We were simulating TB and coming out with new combinations for TB. AstraZeneca was doing the testing on TB in an animal model, et cetera. And we got funded by the Wellcome Trust. Huge grant funding, a million pounds. We got funded by the Wellcome Trust. What is the Wellcome Trust?
00:27:26
Speaker
Welcome Trust is the world's most famous science foundation based out of London. Before Bell and Melinda Gates, they were the largest foundation to fund science and the most prestigious. It comes from the Welcome Foundation, which funds areas that nobody else will touch.
00:27:47
Speaker
areas like infection don't have enough investors, right? It's funded through... Yeah, or Malaria, like Pope. Malaria is TB, any of the Pope, exactly, right? Which is why we are in the situation we have with COVID. Because we don't have early preparedness to keep an antiviral or an antibacterial or an antifungal ready. So the bad day comes with preparedness. Because we say bad day won't come.
00:28:10
Speaker
Much more money in diabetes, much more money in hypertension, much more money in depression. Why waste your time about infection? When it comes, we take care. And that's why we are here.
00:28:21
Speaker
So with all of this going on, that was a very successful project. How we brought modeling and AstraZeneca together. And it took me a year and then we convinced them my management. One quick question on the product. So essentially it was like the same approach where you would need to get some genomic information about the TB of a patient and then give a customized solution. Very different. The mathematical modeling approach is the same.
00:28:51
Speaker
But the translation is very different. What we did in TB choice, we actually mapped out the traffic map of the bacteria. Just like we mapped human cancer biology pathways, we mapped the pathways for the organism, TB, which is millions of years old.
00:29:11
Speaker
And then we put the drugs on it and simulate. Because in TB, you need four drugs for therapy, A, B, C, D. It's a combination of four, quad combination. So very complicated. There are about 27 drugs and you have to use 27 drugs in combination of four. So you can imagine the computation space.
00:29:34
Speaker
27 and within 27 you come out with 4, 4, 4, 4, 4, 4 and within each of those 4 the drug concentration is different. So the permutations and combinations are mind-bought. Millions of mind-bought. Millions, exactly. We simulated those millions of options in cellworks. Picked up the top 10 that said, oh this 4 top 10 look very interesting combinations.
00:29:59
Speaker
AstraZeneca tested it and we published it. We couldn't take it forward as a product because there's zero money in TB, right? West doesn't care about TB and you can't monitor it. And this would be a one-size-fits-all. Yeah, because genomics are not playing a thing here. Because in infection, when you come out with a vaccine, it's for all of us. If you come out with an antibiotic, it's for all of us, right? So it's like that.
00:30:24
Speaker
Day will come when the antibody you reuse may be slightly different than me, but we are not anywhere close to the day. By the way, that day will come when we study microbiome.
00:30:35
Speaker
where your gut, the signature of your gut is different than the signature of my gut. And we will pick and choose the right antiviral and antibacterial based on how your gut looks like versus how my gut looks like. Just like genomics, revolutionize cancer therapy, microbiome, study of our stomach bacteria, bugs in our gut, revolutionize every
00:31:02
Speaker
medical field, not today, but in about 15 years from now. So we spun out bag words from cell words and said, Akshay, we're going to come out with a new antibiotic. Because we saw people are dying. No new antibiotic since the 1960s. 1960s. Because it's all generics. No new class of antibiotics. We said, bloody hell. But one quick question here.
00:31:31
Speaker
Can you give me a quick historical perspective of antibiotics? I know about penicillin, which I studied in school, like penicillin is the first antibiotic, just for setting some context. What's been the development since penicillin?
00:31:45
Speaker
pattern innovations ever done in humanity. Antibiotics is one of them. Yesterday, I just read this yesterday, along with the steam engine and paper comes antibiotics. It is so important. Before antibiotics, average human life was 26 years old. Our forefathers were dying, even in the West.
00:32:04
Speaker
even doing gardening. So you get a small scrape from a rose thorn, can become infected, game over. In India, even post-independence, we were dying in our 20s and 30s mainly because of infection. If you go back to your grandmother or grandfather, they'd say we have six kids out of that one kid died when she or he was two or three, diarrheal infection or pneumonia because without anti-biting, she would take me.
00:32:30
Speaker
The most important innovation of the 20th century is Alexander Fleming's fantasy, which he found accidentally. And once it became a real drug, World War II, 1940s, it changed the world age. One innovation changed the world age from 20s to 40s.
00:32:47
Speaker
right and then the rest is history and then there's been hardly seven to eight classes of antibiotics that have been invented ever since Penison because the antibiotics last for 30 years and then drug resistance picks up you whack it.
00:33:02
Speaker
So, after this was going on at the golden ages, 1960s, where lots of fifties and sixties, lots of the antibodies that you and I and our family use today came from the 1950s, sixties, and then plus one plus two plus three plus four modifications of generations for that.
00:33:21
Speaker
Because the last 20 to 30 years we have abused antibiotics as societies, overused it, used it in our milk, used it in our food, we overuse it everywhere. And as we know innovation in antibiotics, we are in a perfect strong. Your enemy knows all your weapons.
00:33:40
Speaker
The weapons have therefore become weaker and you have not invested in weapons. That is the antibiotic situation. And in countries like India, where the last most important antibiotics are used as soon as you walk into the hospital because nothing else works, we have lost ammunition. So the drug resistance rates can be 50, 60, 70%. That means when you say drug resistance,
00:34:04
Speaker
If 100 people are infected with a particular bacteria, 50 of them will not be cured with the existing, with the first-line antibodies. That's a 50% drug resistance rate. Then you have to go for the highest antibody, which is supposed to be used only for a rainy day. That rainy day is already here. And we're having plenty of rainy days and what you thought you can only use for the worst
00:34:27
Speaker
enemy you have started using regularly. So you are left with very few bullets. And the big pharmaceutical company doesn't want to work in the space actually. This is the superbug. When bacteria or viruses acquire resistance
00:34:42
Speaker
that makes them shield existing therapies. They are called superbugs. I started working on bacterial superbugs. SARS-CoV-2 is a viral superbug. A viral superbug has this dramatic rise and fall like we are seeing with Delta, Omicron and all that. A bacterial superbug pandemic is a slow boil.
00:35:05
Speaker
It's like fast cooking versus slow cooking, where you don't think of it as a pandemic, but it's slowly killing people every day. Just so that your listeners know, every year we lose probably close to 3-4 lakh people in India, 3-4 lakh year and increase, of which 100,000
00:35:24
Speaker
are babies less than the age of 21 who die of neonatal sepsis bloodstream infection before the age of 21 days. We said nobody is going to fix it.
Challenges of Innovating New Antibiotics
00:35:36
Speaker
Wes doesn't care about it because the science is hard, the money is not, is questionable. Can we build a company that can create the first novel broad spectrum antibiotic that the world has not seen in 50 years? That audacious goal is buckles.
00:35:54
Speaker
What is the way in which a next generation antibiotic gets created traditionally and how is bugworks doing it differently? So like you told me, 60s, 70s was the golden age where new generation antibiotics got created. How were they created? How were they an improvement over penicillin?
00:36:10
Speaker
And then you could follow this up by how is bugworks doing the same process of creating the next images. Sure. Very smart question. Try to keep it as simple as possible so we can, you know, so it's palatable to all. So the 50s, 60s, et cetera, golden age, they went after targets because at the end of the day, how do you kill a bacteria or a virus?
00:36:34
Speaker
You have to understand a target and then you have to figure out drug that can go in and hit the target and kill the bacteria. It's called an essential target, essential to life.
00:36:44
Speaker
But it's also got non-essential targets. That means even if you knock those off, the bacteria knows how to live. Because they have been there for billions and billions of years before humans came here. So the adaptability, the evolutionary intelligence of viruses and bacteria and fungi is a million years ahead of us. Because they've been developed before us. And so they've evolved, evolved, evolved. And one of the big problems with
00:37:12
Speaker
environmental warming up and us losing all the ice in the polar cap. There are many frozen bacteria and viruses that are getting released into water streams because these things are melting. This is scary. Just for your listeners to know that superbugs are very intimately connected with environment. You get warmer, oil, purana ice melts,
00:37:36
Speaker
Things that were up for tens of tens of hundreds of millions of years get released into water streams. We don't even recognize those things. It is amazing that how environment that all of this is connected. But do you have a question? And these superbugs are superbugs because we don't have immunity to them. Whereas existing bacteria we have some immunity.
00:37:57
Speaker
Exactly. Just like with SARS-CoV-2, you and I and all of us were worried about SARS-CoV-2 because there were no antibodies in our body. Therefore, we took a vaccine to create those antibodies. Once you get exposed to SARS-CoV-2, even new variants, by and large, your body says, I think this thing is related to that enemy. Let me take them out. When something gets released from Arctic or Antarctic that we don't even have in our textbooks,
00:38:26
Speaker
who the hell knows what's going on, right? So, using targets of bacteria and putting millions of compounds and trying to see which of my compounds hits the target was how drug discovery was done. That failed and it's too expensive. So, 70s, 80s, now people abandon that in infectives, in anti-infection because they say a generics are doing a good job. I think these antibiotics, old Purana antibiotics will last us forever.
00:38:52
Speaker
Why put money into antibiotics? Because remember, you take antibiotics only for five days.
00:38:58
Speaker
and then you never take the antibody. Whereas if I'm a blood pressure patient, I take it for life. If I'm an insulin dependent person, I take it for life. So pharmaceutical company likes a customer who comes for life as opposed to somebody who takes an antibody five days. Then the company would also put pressure on keeping price low. Exactly. Keep the price low. Plus, actually, when my new drug comes, I don't want you to use it. I want you to keep it in lock and key
00:39:27
Speaker
So when the bad pitch in comes that one day,
00:39:31
Speaker
where none of the existing antibiotics are working, you open the safe and take my jewel and use it. Great value to society, but very low revenue. You see? So pharmaceutical companies said, boss, forget it. We're not going to do it. So we also, when we started BugWorks, we cannot just go back to those old screening techniques and say, give me the targets I was just through. That didn't work. So we used very intelligent modeling and simulation.
00:40:00
Speaker
And we went after very interesting concept called efflux. E-F-F-L-U-X efflux. Efflux are the pumps inside the bacteria that kick out antibodies. They're like the bounce in a bar efflux pump. E-F-F-L-U-X efflux. These pumps are very intelligent inside the pump, right? Inside the bacteria. Antibody comes in.
00:40:29
Speaker
What does resistance mean? The bacteria knows how to break that antibiotic. Typically, it changes the target itself. So you're going to say, I'm going to hit the bullseye, but the bullseye moved away and you're still hitting the same way.
00:40:43
Speaker
You lost the bullseye. Or this pump is so smart that it turns on as soon as the antibiotic comes in and kicks the antibiotic out of the pipe. So we did a lot of modeling and simulation of this pump and came up with new compounds, new chemistry.
00:41:02
Speaker
that are sort of invisible to the pump. That's the key area of work of bug works is, can you come up with new chemicals, new molecules designed from Bangalore for the world that enter the criteria? Number one, to hit the bacteria in a new target, because you can't go to old pore arcana targets because those are already changed, find a new
00:41:27
Speaker
new duck board basically create a new duck board with a new target and three can you avoid the bump who's a security guard so because you want to be invisible so the security guard is so what are the three complexities entering the bacteria is super hard but we are not the first people to break that so we use a lot of rules from before two we are looking for new targets in the bacteria
00:41:53
Speaker
And actually the targets we hidden in the bacteria are common across most bacteria. That's why we became broad spectra. Because if we hit the target very specific only to a pneumonia bug, then it may not work for urinary tract bug.
00:42:11
Speaker
Whereas if the target is the basic essential life target, then you cover many bacteria and you become a bronze factor.
00:42:28
Speaker
What is this target that you want to hit from a medical perspective? How does an antibacterial make a bacteria cell die? What is that target it is hitting? Typically, there are only handful of ways. You go in and hit the cell wall.
00:42:44
Speaker
right? You hit the cell wall and puncture it. That's one way. Once you puncture it, then that cell dies. Once everything is gone, the cell can't divide. It's gone. One is you weaken the cell wall that the cell wall loses some of its capabilities. And because of that, it becomes very wonky.
00:43:01
Speaker
Next, you go inside and hit a target that is essential to the life of the bacteria, such as you hit the target that produces its food, you hit the target, which is protein synthesis, or you hit the target that is a very DNA replication machinery. So there are some handful of targets that you hit. And basically, you have to prevent the bacteria from dividing. Even if you don't kill it,
00:43:30
Speaker
You prevent the bacteria from multiplying and then whatever is there will die off. Even if you don't kill it or you kill it aggressively. We have taken the killing approach. Okay, then we go in and boom just hit it and kill it. What we did, we hit a target that impacts the DNA replication. We prevent the bacteria from replicating it.
00:43:56
Speaker
So we went in and, you know, how the DNA has got multi... dual strand DNA is there. We prevented that strand from looking like a strand so that it can't allow for the multiplication in the next generation to happen. And humans need 25-30 years before you produce an offspring. Bacteria is multiplying in 30 minutes. That's why somebody who gets a bacteria infection quickly develops fever and keep that.
00:44:26
Speaker
So we as bad works are proud to state that we are hitting the DNA, DNA engine of the bacteria and preventing it from replicating and we kill it. We actually kill it. So that's been a very powerful target and this target is available across many bacteria.
00:44:45
Speaker
You do both, like prevent replication and also kill? Yes, we are called as bacterial side. Actually one leads to the other in our case. We go in and interfere with the ability for the organism to reproduce and therefore it has to die a natural death. Yes, because their lifespan would be again... They can't replicate it. If there's no DNA replication engine possible, they're gone.
00:45:12
Speaker
Right. And how do you arm your molecule with the stealth technology? That's a patented methodology that we use. We have a phenomenal medicine chemistry group. He's a genius who figured out new rules of chemistry never done before that prevent the pump from recognizing that an antibiotic has come.
00:45:43
Speaker
And once we published it, it looked like very simple stuff. Most great research is actually very simple once you boil it down. But it's that first aha moment to say, I found something that nobody else did. And Shahu Lamid, our medicinal chemist, is the one who did, who broke this. And essentially it's like a camouflaging technology. Exactly right. It's a camouflaging chemical technology. And it works beautifully so far.
00:46:12
Speaker
If our drug is successful and it comes to man, back to the day we will figure out a way to break that also. It will figure out new pumps or the pumps will become intelligent and say, oh, I missed that. Now I am Mushar. Now I am Mushar. I understand this. They are far superior to us. But every time you invent something like we are doing, you buy humanity 30 years.
00:46:38
Speaker
And you say, don't worry, bad cases. I'm that time out. Don't worry. You're not going to die. I'm going to save you. And then you keep working. Use your drug very sparingly.
00:46:49
Speaker
Therefore, there is no economics, so that's a separate discussion. But treat it like a medical infrastructure that you use rarely, like a fighter jet, that you spend billions of dollars on, but you use it rarely for that war, which means we need to figure out how to compensate antibiotics like a fighter jet. That's a discussion that we have with governments.
00:47:11
Speaker
We have no volume, but we have huge value to society because we are medical infrastructure. We are not insulin. We are not blood pressure drawn, but huge value. But huge. We are so excited. If this works, we're going through early critical trials. We have a chance to protect the human race against a bacterial pandemic.
00:47:34
Speaker
Okay, so like you're telling me that 50% of people who get a bacterial infection don't respond to traditional drugs. So that is because of the person or because of the type of bacteria that they have got.
00:47:47
Speaker
It's both related, these drug resistance videos. When we start taking too many antibiotics, it promotes drug resistance. Simply because when you take an antibiotic, any bacteria in your body that is sensitive to that antibiotic will die. It's sensitive, so it dies. The fellows who stay back are resistant. And they sit quietly there. No problem, they sit quietly. But when they become rogue,
00:48:15
Speaker
If they become rogue and you take the antibiotic, the antibiotic doesn't work. That's what drug resistance is. Therefore, by any time you take antibiotic, it naturally promotes some resistance. It's just natural Darwinian selection. What remains are resistant by Darwinian selection. What is a survival of the fittest?
00:48:36
Speaker
It comes, Darwinian, that intelligent comes from bacteria, right? Survival of the fittest. That is why you and I somehow figured out ways to survive harsh temperatures, right? Because survival of the fittest. So resistance is developed by the bacteria to the antibiotics. So people who abuse antibiotics
00:49:02
Speaker
have a tendency to have more resistant pathogens in the system and that resistant pathogen gets spread into the environment every time
00:49:13
Speaker
The person passes urine or coughs, etc. So, you are promoting the spread of resistant bacteria. The person is not resistant or sensitive to antibiotics. It is the bug inside us. Got it, got it. But two people could have the same bug and one case it could be a resistant bug and then the other person it could be a treatable bug. Is that possible?
00:49:43
Speaker
Very rare, not impossible, but very rare. What can happen is one person's immune system can be better than the other. You understand? So my natural immunity could be better. I may have seen that bug, but you didn't see it. So my body may naturally have antibodies to fight that you don't have.
00:50:04
Speaker
because our D cells and B cells and memory cells, the same cells that we spoke about in SARS-CoV-2 are constantly working to keep you and me safe. And does good bacteria help kill bad bacteria? Is there a benefit of good bacteria? Yes, there is a very important microbiome signature going on in his stomach.
00:50:26
Speaker
and there is some healthy competition going between viruses and bacteria in the stomach etc. So, there's a fabulous symbiosis that happens to keep everything in check but this biosis can also happen and particularly when people have no immune system coming through surgery or I'm going through chemotherapy or I'm in a hospital environment, when your guard is down
00:50:52
Speaker
bacteria gets into you. The same bacteria that yesterday couldn't have done anything to you. Today has become rogue. Same bacteria. Right? Which is why bacteria, when a virus comes in, including SARS-CoV-2, it weakens your system and allows the bacteria to also get it. That's called secondary bacterial
00:51:14
Speaker
Okay. Okay. Okay. Got it. So which is why if you abuse antibiotics, then it also like would kill your good bacteria and promote the bad bacteria and make them go rogue. Yes, absolutely correct. So exactly. Couldn't agree more.
00:51:32
Speaker
So tell me about how you went about setting it up. Did you get angel investors in this and what is the commercialization model for it? Very different than Cellworks. Again, hugely challenging because there are less than four companies in India doing novel drug discovery.
00:51:53
Speaker
where you go after a novel compound, you're not doing generics or biosimilars, novel, novel target, new mechanism, so many new things, right? It takes 10 to 12 years, probably half a billion dollars by the time you're done, high risk, and there is very little precedence. So the message and the messenger all have to be at top guard.
00:52:19
Speaker
and have to be really, really, you know, on your toes. And that's the type of messaging we did. We got some fascinating early angel investors, including Kiran Mazumdar of Payako. Friends and family from Bay Area and Bangalore again. The Featherlight Group, who are into furniture and real estate in Bangalore, said, hey, you're doing something for betterment of society. India has changed. People have made money through tech. And now they want to give back.
00:52:50
Speaker
Through philanthropy, they also want to give back by saying, hey, maybe I should fund deep science, deep tech, which 20 years ago, they would never have done because it's like, oh my God, this is, let's solve it. It's not my, I don't need to solve it. Today, India wants to solve the world's problems. So there's some early investors who said, you know, we'll put small amount of money. And then our first round of funding, we raised through Baxter, which is a company out of Chicago, who was visiting Bangalore and we met them in Biocon.
00:53:17
Speaker
Okay, how much did you raise from Baxter? Okay, the first round of funding was $2.5 million. We raised in 2016. $1.5 million from Baxter and $1 million from friends and family. Then our first round of series A happened in 2018 with a Japanese investor.
00:53:35
Speaker
called University of Tokyo Edge Capital, Japanese. First investment they were doing in Indian biotech was ours. 2020 was the second Japanese investor. And just three months ago, we closed our funding series, B1 round, for about $19 million, which sounds like big money, but it's not for drug discovery. But from an Indian drug discovery perspective, it's one of the largest fund raises. Let's start.
00:54:01
Speaker
So to date we have raised about including our grants about 40 million dollars, 40.
00:54:07
Speaker
of which about 12 to 14 million is free money through grants, competitive grants we have won across the world. From foundations? From foundations like the Wellcome Trust, like the United States government that is very worried about superbugs and other foundations. We got some early support from the Indian government through grants. And the very incubator that we are sitting in Bangalore is called CCAP.
00:54:33
Speaker
Center for Cellular and Molecular Platform, C-C-A-M-P means Government of India and Government of Karnataka Fund. So without that kind of government support, well, we couldn't be doing what we do. And the financial section, we asked a question. Typically in biotech, you crack, you crack the innovation, but you don't know how to do clinical trials because that's more of big, big pharmaceutical companies for it. You crack that early science.
00:55:00
Speaker
And then you take your product up to phase one, which is safety, and then a big pharmaceutical company takes you. But in antibiotics, there are very few big pharmaceutical companies. So we have to figure out our own way of blasting new trails and taking a product to market. So we hope to do phase one, phase two, phase three, launch the product in markets like India that are dying for new antibiotics because of the number of deaths.
00:55:26
Speaker
but partner with pharmaceutical companies for the Western markets, like US, Europe, etc. That's our thinking right now. Let's see, if our phase 1 succeeds this year, we'll have many opportunities to look at commercialization. Can you define what is phase 1, phase 2, phase 3 for people not from the industry? If you want to make drug discovery very simple, the early work that you do in the laboratory is called drug discovery.
00:55:53
Speaker
Then you move to animal work and you start developing your molecule into something that looks like something that is real that can go to man. That is called preclinical development. You go through guinea pig, you go through dogs, you go through mice, aeratics, etc. So it's early discovery, preclinical development and then you go to clinical development. Clinical development is the longest, complex, most expensive thing because you're working with human beings. Phase one means
00:56:19
Speaker
We don't know whether your drug works, but let's make sure that it doesn't cause harm. So if it's when you go to healthy volunteers who are ready to take a shot, they're paid healthy volunteers who are promoting signs, just like the vaccine people who put their arm and say, give me the vaccine, I'll be a volunteer before you like out the vaccine. There are people who are willing to be volunteers to say, I'll try this new antibiotic. It's the first one in 50 years.
00:56:51
Speaker
But it has to be safe. So you have to try it. If your dose is here, you start here. And slowly increase the dose. Same thing they do for vaccines, right? Before the vaccine dose, a small fraction of the dose they would have given to a human first for safety. And then slowly increase up to where you need to be to make sure nothing happens. That is phase one.
00:57:14
Speaker
And that phase two you go to a real disease like urinary disease or stomach infection or bloodstream infection or lung infection. And then you choose a small number of patients to show it's still safe in patients and works. That is phase two. Phase three is the expensive global trial.
00:57:35
Speaker
where you say it should work on Indians, it should work on Japanese, it should work on Caucasians, it should work on African Americans. It's not just, you know, for one race. So it's a multi-site, that is phase three. And then you register your product. Complicated, very expensive, and highly probed failure.
00:57:55
Speaker
Right, right. Phase two is then the placebo like that AB where group A has actual and group B has placebo. That happens in phase two. Placebo happens in phase one also. Any good clinical trial, scientific experiment needs to have a placebo up.
00:58:14
Speaker
Just then you know exactly how you are functioning and something didn't happen out of luck. That's the whole thing that something did randomly happen. So here also we have a placebo where somebody just gets water and one person gets our thing, safe to study safety. Because if the person who got water has a side effect,
00:58:39
Speaker
then it's not because of my drug, right? It could be because the person administering it did something bad with the needle and poked around and caused an issue. It is to eliminate that kind of thing that you need a placebo.
00:58:52
Speaker
So it's not because of the active compound. Very interesting, isn't it? And the phase 3 trial where you are testing across the world different kinds of populations, you need that even if you are just going to launch it in India, you would still need to do phase 3.
00:59:10
Speaker
Very good question. Yes, at least we are thinking United States and India because US is a huge market and need. And we are also a US company. Funding is also from the US. And India, we are emotionally attached to India. This is where many, most people are dying, so we want to launch it here. It is good to have multiple sites when you're going through clinical trials because you learn so much. You know whether it's working across a race, et cetera. But if we find a partner in India,
00:59:40
Speaker
Akshay, who says, forget the West. We are losing most people in India. Give us the drug. We want to accelerate it for India. Then India may be the first market for this product to launch. Never done before. Typically, you always do it in the West and then re-enter here. Yes. We are thinking of turning this thing on its head.
01:00:03
Speaker
So what is the phase at which your drug is at? Are you at clinical trial phase now or where are you at right now?
Phase 1 Trials and the Future of Bugworks
01:00:16
Speaker
With great difficulty through COVID, through funding issues and COVID issues, we finally started phase one trial in November in Australia. Australia is very world famous during phase one. And again, very few little precedents from India that a brand new molecule is first time going through, right? So we are very worried, very nervous.
01:00:37
Speaker
We're optimistic but highly cautiously optimistic because this thing can change the world if it works. It'll keep humanity safe for 30-40 years by the time new antibiotics come and etc. So we're going through phase 1 trial in Adelaide, Australia.
01:00:54
Speaker
which I hope will complete by Q2 or latest by Q3. Only studying safety and tolerance, tolerability, safety. Is the healthy volunteer safe? Is the healthy volunteer able to tolerate repeated doses? That's all we study. We don't know if the stuff works. Only safety, because remember, do no harm is far more important first than showing that your stuff works. Do no harm.
01:01:22
Speaker
Even with vaccines, what were we worried? We were not sure whether the vaccines are going to stop SARS-CoV-2 from coming. But we want to make sure that it didn't cause some DNA damage in you that impacts your life, correct? That's what we're worried about. Yeah, most people who are like vaccine deniers are because they fear those negative effects.
01:01:43
Speaker
Exactly. I don't want to put my body through it, including Novak. So, if the phase 1 trial is successful, then we'll plan for phase 2 next year. Phase 2 will likely be India and the US.
01:01:59
Speaker
or India and Eastern Europe. Eastern Europe is world famous for trials. Unfortunately, Ukraine and Russia are out of that reckoning right now because of what's happening. But India, definitely. Unlike other companies in the world working on antibiotics where India's later plan. For us, it's part of a plan from day one. Because unmet need is high. We are in India.
01:02:26
Speaker
The drug-resistant patient population is highest in India than anywhere in the world. So we are not doing India fable. As much as we are saying, this is the worst battle is here. So test your weapons in the worst battlefield, not in the five-star battlefield. If it works in the worst battlefield, it's a very good chance it's going to work in other battlefields. So that's why we do it. And we want to give back to India via drug discovery and science.
01:02:55
Speaker
I want to understand these territories, like you said, Australia is famous for Phase 1, Eastern Europe is famous for Phase 2. Why is that? Is it because there are companies there who have grown big and they do this? Australia is famous because of how finding patient population is very hard in Australia because it's partially populated and they don't have an infection problem like India does. But their processes for Phase 1 are very good.
01:03:22
Speaker
As a country, they said, you know what? Everybody who's got a new drug is always worried about phase one. It's a tough one. Toughest phase, because first time you're putting something into man, you don't know whether it's good to work. Let us focus on phase one. And now they capture that market for phase one. Okay. So that doesn't really enable it. Yeah, everything. That means the physicians, the people running clinical trials, the units, how to monitor the volunteers while you're going through phase one, et cetera. They have fantastic protocols.
01:03:50
Speaker
Eastern Europe also does phase one. But if you want to get urinary tract or kidney infection patients, they are plenty fully available in Bulgaria and Romania and Hungary, et cetera. So happens Eastern Europe, not Western Europe. And you do it there, right? Ultimately, you have to go to the US because you want to get a US FDA CHAPA. Without that... Right, because that is the gold standard. Platinum standard.
01:04:16
Speaker
Right, right, right. And why is drug resistance highest in India? Highest is in India for multiple reasons. Traditionally, our sanitation issues are aplenty in hospitals, right? It comes down to hand hygiene, wash, free running water, sewage mixing with drinking water, variety of reasons. We have large antibiotic manufacturers
01:04:43
Speaker
Maybe the manufacturing output is making it into the water stream. So every time we drink such water that has traces of antibiotics that can promote drug resistance. And the fact that you and I can walk over to our neighborhood pharmaceutical shop and pick up an antibiotic without a prescription is devastating.
01:05:03
Speaker
Millions and millions and tens of millions are taking antibiotics without prescription. Then what happens after the first two days, you say, I'm feeling fine. Why do I need to spend money after two days and stop? Not knowing that it takes five, six days to kill all the bacteria. What is left behind is going to again become resistant. You have to, you know, so many reasons. And we are working closely with the Indian government to make it very difficult to buy antibiotics over the counter.
01:05:30
Speaker
Treat it like an anti-depressive medicine or anti-psychotic medicine. Hard to get, only under doctor's prescription. So, abuse of antibiotics, use of antibiotics in poultry industry, damping of antibiotic waste into our water streams, issues with sanitation, hygiene, no innovation. That combination makes India the worst and a density of population.
01:06:00
Speaker
That giving cows and hens that antibiotic shots, this is like a global problem. We don't do it for cows as much as we do it for poultry. Because in the 1960s or 70s, some scientists in the US did a study and figured out that when chickens were given antibiotics, it makes them fatter faster.
01:06:24
Speaker
So for the protein industry, which has gone through the roof in the last 20 years, antibiotic use keeps the hen and beef healthy so they don't get infection because they are in tight corners. So if one thing gets the infection, it spreads overnight. Put all of them on antibiotics, the chance of infection is reduced. But then imagine that.
01:06:46
Speaker
the chicken are having so much of antibiotics, their excreta and their urine is going into the water streams. The people who are working in those industries are coming in touch with those bugs that are getting resistant.
01:07:02
Speaker
That's how the spread happens in soil, in water. Then when you handle that meat in your house before you cook it, it may still have those bacteria on it. So it's tricky. So by 2024, somewhere around that timeframe, you would have gone through clinical trials and be ready to commercialize. No, I wish to. Unfortunately, trials take much longer.
01:07:30
Speaker
Thanks to COVID, there is an acceleration. But if everything goes well, we are looking at a 2025, we have already 22, 2025, whether we can launch in India. And probably 2026 for a global launch. Okay. And what is the revenue potential of this drug? Like what, like, you know, is it like a billion dollar drug or, you know, how will it get commercialized?
The Vision for Affordable and Accessible Antibiotics
01:07:58
Speaker
We want to make it affordable and accessible for markets like India and Africa and Southeast Asia. Very simple. Very simple. We did this company to make it affordable, accessible, but not too accessible. That's the scary part of the Antipody. You want every nook and corner to have it because then you're finished. You need to have a business. Antipody companies are failing because they don't have revenue. You spend so much money bringing product outside and there's no body.
01:08:23
Speaker
So governments are trying to pay a net, what they call a subscription model. That means they say, bugwalls. Don't worry about selling it. We guarantee you that we are going to buy it. And like Netflix, whether you use it or not, they figure out how to create a subscription model.
01:08:40
Speaker
I think the way the world is going, you should be lucky if you could get $200 to $300 million per year from a new antibiotic in revenue after the first six years of launch. But if we are successful because we are a broad spectrum, Akshay, I'd like to tell your listeners with great humility that we have the opportunity for a billion dollar antibiotic out of purpose. Like billion dollar annual revenue? Annual revenue at peak.
01:09:10
Speaker
and it may take five to seven years to reach the peak after launch. Five years to reach the peak.
01:09:16
Speaker
But we are looking, there's no reason why a bug works drug, if it gets to clinical trials, cannot be a brilliant drug. Absolutely, because there's no precedence for this kind of drug, broad spectrum, IV and ORM. So it's available for hospital patients and tablets forms. So like that 2,300 million number, which you told me is for narrow spectrum, like something solved with that. And for limited spectrum, because it's not applicable everywhere.
01:09:45
Speaker
Abroad spectrum can straight away replace 20% of the market in India whose patients are struggling. The carpet bomb them with so many antibodies. You see a single antibiotic. You don't even need to guess what the bacteria is. You claim it. Right. OK. Amazing. And we're also looking at a second revenue stream, which is to become a solution for bioterrorism.
01:10:11
Speaker
The same antibiotics that can help you against serious hospital infection is working on anthrax or plague on very, very bad organisms, which can become bioterrorism situation someday. I hope not. And therefore, we are talking to multiple governments to see if the same solution can become a
01:10:34
Speaker
a prophylactic solution for bio defense. So, it is very interesting that looking at hospital infections, community infections and bio defense. Anthrax is a poison right?
01:10:48
Speaker
Yes, it's basically anthrax is a bacteria. It's poisonous to human body. That's what I meant. It's not like a toxin. It's a bacteria that is inhaled through sport form. And once it's inhaled, it causes your whole nervous system to come. And is it infectious, anthrax?
01:11:08
Speaker
It can spread very easily. So if a bioterrorist figures out how to aerostanize it, they can infect a whole bunch of people very quickly. And then a drug like ours can be used to jab people who are coming into a hospital situation to keep society safe. So it's a stockpiling, more a defense than a public health.
01:11:34
Speaker
in the
01:11:43
Speaker
say a 15, 20 year timeline, what else is on the roadmap for Bugworks? Excellent. So one is we hope we can keep every patient everywhere in the world safe against an infection. Right. And we don't want to lose a baby less than 21 days of age because she couldn't be safe. It's very clear. So we had to be affordable accessible. Yet you need to figure out how to protect and make money. That's on the infection side.
01:12:08
Speaker
We want to be the partner of choice for governments for bio-defence. A drug like RC, if successful, can keep governments safe against bioterrorism even when the day happens. Now, nobody laughs at us when we talk about bioterrorism. Say, hey, that's never going to happen because we've seen what happened with the pandemic.
01:12:23
Speaker
And who knows, anything is possible with microorganisms. Number three, we also got into cancer. We realized that immuno-oncology, which is a new cancer area within cancer, is offering a lot of scope for good patient outcomes. But it's frightfully expensive. So we are trying to innovate. What is immuno-oncology? Basically, it's a new
01:12:47
Speaker
class of oncology that says, instead of putting chemotherapy, radiotherapy of these things, can I figure out how to make your own immune system wake up? And the wakefulness of that immune system causes the killing of cancer, natural killer cells or natural immune system. Because the tumor is so smart,
01:13:08
Speaker
that it locks up your own immune system. It takes your own immune system into believing that I'm fine. I'm one of you. I'm not a tube. Trust me. You can trust me. And it locks up your immune system. So immuno-oncology or drugs that go in and break that lock and release the immune cells to go into the tumor and kill it. Yeah. Okay. Okay. Okay. So basically a tumor is essentially just a
01:13:35
Speaker
Rogue cell, like it's a cell of your body only but which has gone rogue. During replication something went wrong, right? Due to the genetic or environmental or food or toxins that you ingest, something caused DNA. And your immune system normally says, hey, I can't recognize that cell. That doesn't look like Akshay's cell or that doesn't look like Anand's cell. I need to take it out. But still the tumor is growing because the immune system failed to recognize it.
01:14:06
Speaker
And therefore, immuno-oncology breaks that lock and allows immune cells to get in. So it's a hot area. We just got into about two, three years ago, looking very good. I hope we can also bring affordable immuno-oncology drugs to market in. So we have these two large goals, superbugs, antibiotic resistance, and immuno-oncology. That's our goal for the next 10, 15.
01:14:29
Speaker
And what is the timeline for? As a bioterrorist, it's always so tough. So the timeline is in five years time, not even say four to five years, we launch an antibody. That will be a phenomenal breakthrough product for the world, for hospital infections, community infections and bioterrorism against bioterrorism. While you do that, you also keep on working on next generation antibiotics because you know that the bacteria will figure out and break.
01:15:00
Speaker
So we also work on backup acids. And in parallel, five years from today, hopefully we can also have an immuno-oncology acid on the market against very tough tumors like colorectal cancer, lung cancer, liver cancer, stomach cancer, prostate. We are looking at this area, the abdominal lung in this area. Okay. Okay. And how big is that drug, the immuno-oncology drug? Is that also like a billet dollar?
01:15:30
Speaker
Much bigger than antibiotics. It can easily be a $35 billion per year type of market. But there are 4000 assets going through clinical trials. So you're the small needle in the haystack. The competition is fierce because the unmet need is so high and the market is even better.
01:15:52
Speaker
Whereas in antibiotics, we are considered one of five or one of 10 worst case in the world. That is going to correct. If we correct the problem, we are one in five or one in 10. Market is so-so, but impact is massive.
01:16:09
Speaker
And there's nobody from India doing what we are doing, right? Oncology, everyone is there because that's the hottest area. But the market can also potentially soak up a lot of good assets. So it's good for us, right? We have one in which we stand out.
01:16:27
Speaker
But market is tough. So, but we're doing it for impact. In the other, we may stand up, not yet today, but we may stand up, but it's fiercely combative. So, how to position? So, we're using a lot of, we're trying to bring cell works now back into bug works and see whether we can bring modeling and simulation to differentiate our oncology product from others.
01:16:48
Speaker
Got it. Okay. So, you said multiple times about the risk that you are facing over the next two, three years. Talk to me about what kind of risk are there, like there is a risk that the times that it works. I think, exactly right. I'm very confident that by the time we are ready with the product, the market conditions for 90-biotically beef, you know.
01:17:08
Speaker
Thanks to the pandemic, governments are waking up to saying, bloody hell, take this very seriously. Don't wait. Tsunami is coming. In SARS-CoV-2, we didn't see the tsunami coming. It came and hit us. Whereas with antibiotics and bacteria, we see the tsunami coming. It's a slow tsunami. So we have to be prepared. So I'm sure market conditions are OK. Science seriously.
01:17:33
Speaker
In antibiotics, phase one is a tough one, safety, because it's one gram. One gram, right? So if we get to safety, our risk is done in antibiotics. Whereas in oncology, the risk is what works in animal does not work in man, the translation risk, because you and I are far more complex than an animal. And how cancer works and spreads and grows and gets killed in a human is not accurately reflected in the animal.
01:18:03
Speaker
So the animal models are poor substitutes for equipment. Whereas in infection, whether it is a mouse or man, both are infected and you're trying to take out a foreigner in both cases. Whereas in immunology and
01:18:19
Speaker
Oncology and all that, my God! Mouse is a poor substitute for that. But you have to go through the mouse. So, science risk in safety is a problem in antibiotic. Science risk in lack of translation is the problem in alcohol.
01:18:35
Speaker
Got it. Okay. And what will be your distribution strategy? Would you like sell the IP or license the IP to a larger pharma company or do you manufacture it? Yes. A small company in biotech. Impossible. Small biotechs all over the world, the DNA of such companies is you innovate, innovate, innovate.
01:18:54
Speaker
and then work with somebody who understands, go to market, supply chain, manufacturing, distribution, FDA approvals. These are complex areas, but a process-oriented. Small companies are good for innovative, crazy things, but not good for process. So things that require chaos, innovation, multidisciplinary thinking do inside the company. Things that work, process, money, global outreach, you partner. So I think both products will only part.
01:19:21
Speaker
Okay. Exactly. Right. Right. Exactly. So if a Pfizer or a Cipla in India is interested in antibiotics and say, we want to make a difference from India for the world, you partner with it. So you can keep innovating and coming up with a next generation solution partners much stronger than you to complete clinical trials and manufacturing knowledge that is supremely difficult because it has to be done with the highest standards because it's human, human grade.
01:19:54
Speaker
So partner, partner, partner. So essentially Bloodworks is an IP company. Like 30 people, 40 people maximum. Hire the best talent from around the world. Bring in modeling simulation. Bring in technology. Bring in all this stuff and do drug discovery in new ways. And then find the partner at the right place. You find the partner preclinical or phase one or phase two. We don't know yet. We're keeping all options open.
01:20:25
Speaker
We need to make solutions in India for ourselves. We cannot wait for the best two to come and solve our problems. I think that's a new theme that's coming out. What we proved ourselves in vaccines, we are proving ourselves now in drug discovery as well that innovation has to come from our own backyard to solve our own. That's all I have to say.
01:21:06
Speaker
Before we end the episode, I want to share a bit about my journey as a podcaster.
01:21:11
Speaker
I started podcasting in 2020 and in the last two years I've had the opportunity to interview more than 250 founders who are shaping India's future across sectors.
01:21:22
Speaker
If you also want to speak to the best minds in your field and build an enviable network, then you must consider becoming a podcaster. And the first step to becoming a podcaster starts with Zencaster, which takes care of all the nuts and bolts of podcasting, from remote recording to editing to distribution and finally monetization.
01:21:43
Speaker
If you are planning to check out the platform, then please show your support for the founder thesis podcast by using this link zen.ai founder thesis. That's zen.ai founder thesis.