BTI 45 | Translational Genomics

 

Some of the main problems with sequencing in identifying mutations are its cost and the time it takes. Fortunately, with the rapid growth of technology, revolutionary products that simplify processes are being made. One of those is from DiaCarta, a diagnostics company using translational genomics and molecular precision technology to develop ways of detecting disease. In this episode of BioTech IQ, Ammon Rivera interviews its CEO, Adam Zhang. Their patented technology reduces the “background noise” in testing, allowing for the detection of the “bad actor.” Join in to learn the processes behind their work, what this means to the future of testing and treating diseases, and where the company is headed. Don’t miss out!

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How Is Translational Genomics Reducing Background Noise In Multi-Disease Detection? With Adam Zhang

Adam Zhang, CEO – DiaCarta, Inc.

Welcome to the show, Adam. It’s great to have you.

Thank you, Ammon. It is great to be with you.

I’m excited to talk a little bit about your background and some of the things that are happening with DiaCarta. We will get to that point. Again, thank you. Why don’t we kick this discussion off by jumping right into your background and trying to understand a little bit more about the driving factors that led you to where you are now?

I have been training in science in biology, particularly in the medical-biological field, in the past decades. The company we started with my partner, who is still the full-time Chairman in Florida. His name is Paul Okunieff. He and I started the company in 2011. We started with a very interesting DoD grant. This grant is basically called for a device and detection. You can ask about accidents or radiation happening in public. They want to know how many people get more damaged from radiation, how many people get very minimum, and it’s okay.

In the immediate range, like a triage, the population is okay. He is well-known in the radiation oncology field. I’m training in this technology biochemistry field. We came together and came up with an idea. There is a biomarker we found that particular can monitor this event. This is where we started DiaCarta. DiaCarta’s name is all original. The Dia is Diagnostic. Carta means MAPI. The company name meaning is Diagnostic MAPI.

You have some amazing things with diagnostics here.

That’s where we started. Specifically, the goal is we develop a unique biomarker DNA test with unique technology and the specificity to identify this piece of DNA and during this incident happening. It can monitor how many these gamma-GB were received from this instance. Later on, this is the grant that we have down pretty well. This is a long-classified grant, and they recommend us for clinical use.

We continued to develop these, and now is first in class supporter we put on the shelf we called RadTox. These particularly can monitor radiation or chemotherapy for the patient. By far, even so, advanced from the imagery, on the accelerate, to put on being from a lot of the therapy drug but still, 60% of our patients had to go through radiation chemotherapy. They still cannot personalize.

Every patient comes in, given a dose and every day treat. We can break, and the doctor not be able to communicate with a patient until the 30th day when all the treatment is done by image. This is the very first time from their first dose to see a biomarker lumber change, and right away, we know how this patient responds. That’s the way we started in DiaCarta. They are telling that liquid biopsy is very hard. We looked into the demand from the field then we came out with a very cool idea, which is called XNA Technology. We took them all but at least we went and thought of the technology as a breakthrough and addressing this bottleneck in this field.

In a liquid biopsy, the key thing is how to find the needle from the heartache. Share on X

For all the audience, DiaCarta, as you mentioned, you have prepared technology that helps essentially reduce background noise in the sequencing, and it amplifies the sensitivity of detecting hard-to-find mutations, and that technology is being applied to multiple diagnostics. You have the liquid biopsy and the XNA Molecular Technology.

We are discussing RadTox, the ColoScape, and it looks like also for SARS CoV-2 or COVID-19 as well. A test it’s ranking in the top four now in the FDA for the reference panel test. Let’s focus then a little bit on the liquid biopsy test. Explain that a little bit to us and help us understand a little more about what makes this revolutionary.

In a liquid biopsy, the key thing is how to find the needle from heartache. You want to find those mutant DNA or methylate DNA from one to blood. From one to blood, first of all, you need to extract the DNA. We call it cell-free DNA from one to blood. The amount that you could get from cell-free DNA from one to blood is very little. It’s only about 30 to 50 nanograms. No matter what you do, modern technology detects little things doesn’t matter. 2nd generation, 3rd generation sequencing or anything, the edge of technology, the foundation is you have to design the primer to amplify your template.

This DNA is very little. You have to manmade they use called PCR and modify the template to certain lumber and be able to detect it by the tools they use. During the PCR amplification of releasing the template from the DNA you extracted from the one to blood. There are two different templates, many from blood. Ninety-nine percent of our templates are those in the normal DNA. We will call it a wiretap. That mutant template is very little, less than 1% like one bad guy bury all the good guys. It’s very high. They will find the bad guy. Now, the technology, no matter how you are using enrichment and all the different way to do it, so far, they still can’t rely on core sequencing.

The sequencing now, the leader, there’s Ghana Health, and they know what to do. The amounts so far, no much to change, except we call the depths of the sequencing. The sequencing is very hard to find that they need from a hazard. If you went wrong, you could not find it, you do it again, call two times or two wrongs, and do it 10 times to 5,000 times. Now, because of the coping number of those mutant DNA will be buried deeper on the wide to have a DNA to be able to find a particular form of pre-cancer, the common number, which is even lower. Nowadays, if you see data, you are going to find 30,000 times.

That means you cost so much money for the raging and the timing consuming, and at the end of the day, you still have the usually known as complicated biomedics to calculate whether this needs to announce there is negative there. The way we address the issue, we use a very simple solution, and it’s efficient. We call it XNA. It is a piece of chemistry. This chemistry can specificity lock or block those noises in the wild-type DNA. These are called QClamp technology. This piece of unique chemistry can hybridize to the wild-tap DNA, normal DNA, then the enzyme cannot pass through, so this wild-tap DNA cannot be amplified.

If any mutation or those methylation being happened, the way we are designed is clamming, we are barely off. It cannot block this problem, the DNA, which we call mutant template. In this way, the mutant template can be freely amplified. To simplify the wire technology, we have XNAs. Basically, they make all those good guys disappear. Only show up the bad guy.

That makes a lot of sense, though. As you said, you are simplifying and turning off all the background noise and making it easier to find the bad guy, the mutant actor, and the meat in the cells. How do you see the application to this? Are we talking about being able to detect cancer earlier and faster?

The application of this technology is the chemistry platform. They can be applied to any existing instrument and also not only in the cancer field. Any genetic change that is caused by mutation, methylation or fusion, whatever the genetic variant and cause of disease, such as cardiovascular, even prenatal, all the drug resistance. You get HIV, TB, and even now, COVID. The Delta then applies to Omicron, which is caused by mutation. This XNA Technology perfectly can apply to that. That’s the chemistry. As long as we know where the mutation happened, and we know this is where it caused the problem, we specifically design XNA to remove all of this noise.

BTI 45 | Translational Genomics

Translational Genomics: To simplify the wire technology, we have XNAs. Basically, they make all those good guys disappear. Only show up the bad guy.

 

Specifically, amplify the problematic one, the template, then can easily detect it. These detected the use qPCR phase or be using nanotechnology like a bead space or can be used array also can be in a sequence. You don’t have to create a new instrument because to use exists instrument, which has uses this normal chemistry and to be able to achieve the goal. This is quicker. You don’t have to wait for two weeks, deeper sequencing. Mostly those people do very expensive sequencing. They can do this within two hours. We made these a product kit. We call this kit ColoScape.

Use XNA Technology, and though to a specificity, find a mutant DNA that would cause you colon cancer from blood. We pre-med everything to the PCR reacting tube, and when the technician receives this, they can either the DNA will purify from the blood and add a tube, and put it to the PCR machine. It doesn’t matter if a PCR machine is from Roche, Barra, or API. Within one hour, it will give your results. The cost of these is very low. It’s more like in the current day for the sequencing costs of the hundreds of dollars, even a thousand dollars.

This is one only cost $200. It’s very affordable to order. Common patients or people can afford to use it. Precision medicine has advanced so far. We see the big problem is that the cost is still very high. Not everyone can benefit. The goal for DiaCarta is we use our unique technology and then make it a product. This is a high-sensitivity, high-specificity but with low cost to benefit all the people. Not only the 1% people.

Let’s back up a little bit. You designed your technology, which you mentioned as chemistry. You have designed it to be used on other machines that already exist. You can plug it into the existing system. It’s not a massive cost that affects the lab, the insurance, and ultimately, the patient. They can then have access to this. Can you hold the box up real quick? One more time to get a whole view. Is there anything written on the front of it?

It’s called ColoScape. Our product is a colon cancer screening test. The 1 box can do 24 patient.

You said that box costs $20 or each test is $20?

Our raw material manufacturer costs $20. Now, in science, they reimburse for over $500. Our costs are low. We apply the code for reimbursement around $300. It is much cheaper than the current one but we are cheaper than sequencing. If you do deeper sequencing, it will cost over a thousand dollars, if not more.

It’s a longer process on the sequencing test versus the XNA technology that turns down the background noise and allows you to find the bad guy faster.

That’s right. Also, you can get results. You can get a seven-day report instead of waiting for a week.

Precision medicine has advanced so far. The big problem is that the cost is still very high. Not everyone can benefit from it. Share on X

You are already on the market with this and moving forward in terms of commercialization?

We extend technology and perfectly demonstrated this during the pandemic. Before the pandemic, we heavily invest in technology for cancer and other diseases. People will see, “This is a very cool technology but how can you handle the scale or a real product in the medical field?” When pandemic is happening, we quickly jump on to fight the pandemic that use our technology. We developed a product. This product got FDA approval, and also we can make it easily on a scale. Normally, for IVD, particularly for diagnostics donors, if you do, say, 50,000 tests monthly manufacture, that’s already big enough.

Now, at these pandemic scales, we haven’t to do two million tests monthly manufacture. These already demonstrated that the technology is solid and can scale up, also, for lab testing. Normally, you can do your 500 tests in a week, and that’s already a lot for cancer. Now you have to do 5,000 samples a day. This is also demonstrating that you can be scaled up. This is a very good demonstration. The technology is solid and addresses these in many markets.

I wanted to ask a question if you wouldn’t mind maybe sharing a little bit of knowledge with us. On BioTech IQ, I have had other individuals on. We talk about diagnostics and what they are doing. A lot of times, the people that I’m interviewing are people that specialize in, say, drug development. They are developing some type of a therapeutic. The process for developing a therapeutic or drug treatment is much more lengthy, and the process is longer. What I’m getting to, though, is the differences between developing and getting a diagnostic technology like this approved versus getting a drug approved.

Let me give you an example. In my mind, I view the drug development process of discovery, the pre-clinical work, IND application, Phase 1, submission at the end of Phase 1, approval to go to Phase 2, Phase 2 submission, and Phase 3, backing up to Phase 2, and sometimes a Phase 2 B. You do a pivotal phase three study then you get to an NDA. If there’s an approval there, now you have the whole commercialization process, and then post-market. When I view drug development in my mind, I see that process. When I view diagnostics because I don’t understand the process, I don’t know how it works. Maybe you mind sharing with us a little bit about the process of what the steps are generally.

The people outside in the field are mostly, as I said, are in the drug development process. Not so much for me now with the IVD diagnostic. When precision medicine comes out, the diagnostic is more important. Target therapy now, the first thing is you have to find the mutation, finding the problem, and the tail, which dry can use. This is called Companion Diagnostic. This is also our technology. One big part of it is an open platform to have a drug from biomarker screening to find out which biomarker is causing the disease, then working with the drug company while they do a clinical trial where we focused on IVD and develop a kit. The goal is to drag it together.

Any drug you use before they drug you, they have to test this before you use the drug. This is called Companion Diagnostics. To your question, the IVD is called a medical device. It’s different from drug development. Although, the Companion Diagnostic will be closer to a drug developed in each stage. For the IVD, a medical device always depends on the risk of the product itself. FDA may classify a called Class 1, Class 2 or Class 3. Class 3 is the highest. You handle the big clinical trial. That’s anything related to cancer. All doctors who use your tests and make a decision automatically go to Class 3.

Particularly photo screening, a colon cancer screening is automatic Class 3, the PMA. In this way, the design depends on what’s the purpose of your test. If your test says, “We want a confirmation.” We want from your sample or either tissue or blood. We want to confirm from the tests that say you have the cancer. All you have on there is any disease. That’s the call regular Class 3. You will probably need 1,000 samples to confirm the test is consistent with other tests existing way. Overall, the tests don’t need to be in Phase 1, Phase 2 or Phase 3. That’s only called Class 1, Class 2, or Class 3.

Depending on each class, the requirement that clinical trials are different. For the trial, they don’t go to a Class Phase 1, Phase 2 or Phase 3. Basically, it went a pivotal trial. In the IVD field, they are called what you say, say what you do. The criteria for FDA approval, Class 2 will call the Fountain Kit. The Fountain Kit is if your tests are equal to or better than the golden standards, the existing one, you will get approval. There is no risk. If you have not paid or you go, then that’s the kind of one, so you won’t get approval. The equal or better than the kind of one they will automatically get approval. That’s the full Fountain Kit.

BTI 45 | Translational Genomics

Translational Genomics: Biology is not easy. It’s a long process to work in the field.

 

For PMA, Class 3 is new. You don’t have anything to compare with that but you can compare it with the golden standard like in the pathology for colon cancer in this case. The golden standard is a colonoscopy. The test that you can compare, the traditional one, is called the FIT test, which is a very low-tech test to find whether your stool has blood.

If your test has blood in your stool, it doesn’t mean you have colon cancer. That’s why we have the colonoscopy to confirm but there is a new way to do it. Usually, medical diagnosed it, to be more precise. You find the problem before you can do a colonoscopy. In this way, you have to design a large one based on the incident or prevention of colon cancer.

Every 1,000 people out of 6 potentially have colon cancer. This is a calculation design trial of over 10,000 patients. It’s a big trial. To be able to demonstrate it, your product can pick up those problems from the health group. Even that doesn’t do Phase 1, Phase 2, Phase 3. Only one pivotal trial and your prime employee and say, “What’s the FDA of teams that you set out?” You say, “I will send the FDA to 90% to call it.” This is a stage 1 cancer. If you meet that and the specificity is more than 90%, then you get approval.

In drug development, the FDA, at the end of the trial, is looking for the acceptable risk and safety profile. I forget the exact term but they are basically looking for significant proof that it makes a difference in terms of the treatment of the disease. In the situation with a diagnostic device is, you are looking that you can have in this situation of Class 2. You are looking, can it do the same or better? In the case of Class 3, is it 90% effective or better in terms of detecting? How do you control those endpoints? For example, you said that you do one big pivotal trial, the diagnostic that you are testing. In addition to that, go and get this. The gold standard that’s on the market now, and they compare that.

Steal is a golden standard to compare.

On the same individual?

Right. Again, back to colon cancer in this case. The same individual comes in. You see, the patient has what we call the FIT test, the stool tests, on whether they have blood in the stool. They are going for a colonoscopy to confirm whether they have colon cancer. We don’t know. These are the blind. There’s another population that’s a dual separate. You take 1 or 2 blood to use in our kit test then results come out of whether this person is negative or positive.

At the end of the trial, this is the tradition in DiaCarta company, the better we don’t know. They are going to an appointment to do a test analysis. Let’s see whether it’s on the TBTs festivity. The need at the beginning, we agree with FDA. If we meet or pass that, you get approval. If it does not meet, you need to extend the trial, the more patient, the more you fail.

I appreciate you taking the time to explain that to me and to the other audience that is out there. Some of them probably are familiar with it. Some of them may not be so much. It’s great. It fits into the picture here of the biotech industry as a whole. Understanding I’m developing treatments and developing diagnostics.

Prevention is the key point of a global issue. Share on X

Ultimately, my diagnosis is going to help me find who needs the treatment and how the quicker we get to them, the better the outcome, most of the time, especially things like cancer. The earlier you catch it, the better your chances are typically so. What’s the future for DiaCarta, then? It sounds like you have discovered a piece of technology that is pretty amazing in being able to detect. How do you see the future of this in terms of the growth of the company and all of that?

This is a very exciting time, particularly during the pandemic. We put all these biotech for liquid biopsy IVD in front.

We recognize the need for better diagnostics.

This is very good timing, although, in the past years, we are working non-stop without any one-day breakthrough in the pandemic. At the same time, we are very appreciative and grateful for the opportunity to demonstrate our technology. Also, the whole field is getting more attention and publicity and is increasing compared to years ago.

At this point, we call these opportunities but as a company, it doesn’t matter even bigger than our size. You cannot do everything. We know where we are going, and in the short-term, we focus on a few things to get our product in the market and to have more patients use our product. Not only in the US but in a global penetration and particularly our technology costs are low and with high precision.

If our emerging market for Third World can also benefit, this is for precision medicine. Not only for advancing the country benefit for precision medicine. That’s our main goal. For our short-term goal, we continue to find during the pandemic with our normal technology and bring more products to the market like Omicron, variation tests, and other things to do. Also, we started resolving cancer and infectious disease, and other things. We are bringing it up a normal life for people which has cancer problem. Particularly now, as you say cancer, you find earlier prevention. Prevention is the key point of a global issue.

Only find that the survival rate is very high and with a very low cost, interrupt, and not waiting for middle and later stage. That’s our sweet spot. We continually make an effort to put more products on the shelf. Not only for colon cancer but more for lung cancer, breast cancer or other cancers, then we can move to cardiovascular and other fields.

That’s a continued effort to take advantage of our technology and to put a product on the shelf but also grow our company not only for diagnostic. As I mentioned, our XNA will also be suitable for therapeutic. Our dream in the future is to make this company to a solution from diagnostic to the therapeutic platform. That’s making these unique for the DiaCarta image market.

That one platform, from diagnostics to therapeutic would be an interesting take on the process and the whole thing. I was going to ask, you are located in the Bay Area at DiaCarta’s headquarters and also in China, correct?

BTI 45 | Translational Genomics

Translational Genomics: All of this biotech will continue booming and need a lot of newcomers and funding to support it.

 

That’s right. We are in China, Italy, and Europe.

The EU, China, and the US, you have expanded your growth there. Are you already on market in those countries?

We are already in the market in Italy too.

It’s a different process for each country, which makes the world of biotech challenging, even in, as I mentioned, drug development. It’s like, “I’m dealing with this regulatory authority, and they have their way of doing it.” It’s a challenge. I would like to shift the conversation here to three questions that I like to ask all my guests when they come to the show. They are interesting questions for some people. We will get started with the first one if you are ready for that.

Sure. We will see.

I woll try not to throw curve balls here. The first question is if you could go back to the start of your career, what advice would you give yourself?

It was quite different from many years ago and now. The time when I started my career was not so much my personal choice, which is by my parents, “This is the girl called Adriana. Take this major and do these.” Biology is not easy. It’s a long process how to work in the field. For your career, if you are persistent, explore, and put in an effort, you will see the outcome. This is a very unique field, not including the medical too. It’s hard work. For the people to start a career or particularly for college, it’s an exciting field but also be prepared. No shortcut. It’s long-term, a lot of hard work, and you have to have passion. To do these, you will be able to achieve that.

The next question has to do with books. I’m curious to ask you this question because I know your background is from China. A lot of individuals here in the US, when I ask about books, I get a pretty good range but there’s a certain book that I hear people mention often. When you are in close proximity to other people that may be read that book, then they recommend it to you, and you read it, then someone else. It spreads, whereas it’s nice to hear of other books that I have never heard of before. Maybe, maybe not but I don’t know if you get much reading these days but what book or books have you read that you felt have had an impact on your career or life?

I read it quite differently. Nowadays, I get less time to read it. One book is Zero To One. That’s a very good book, particularly for people that want to start a company or a business. It’s helpful.

For your career, if you are persistent, explore, and put in an effort, you will see the outcome. Share on X

It’s focused on the early stage. Starting at zero, then going into. I wrote that down. I write a list of all the books. I was telling one of my guests, I have a list of books. Sometimes, I look at it and I’m like, “I don’t know if I will ever read all these in my life,” but I write them down and try to look at them. The last question I have for you is, where do you think the biotech industry is headed?

The biotech industry is still going strong. It doesn’t matter if the economy is good or bad. This is a medical field, a battlefield that is still on its pace. They will continue and are going. This is a very promising field. Moving forward, every five years, you have seen new technology come out, and these new treatments come out. This is ongoing and endless. All the scientists and a lot of hard work continue to put an effort in this field. There is more to watch you different major combo like the use of AI, the different software, and Telemedicine to combine with an aware lab.

This is getting more mix in this field. That would take advantage in all the technology in different fields to address this medical issue. That’s definitely getting more hard area. This personal medicine is the way to go. We know every person doesn’t know that everything is different, how you can get technology, all the treatment, to fit it in all the variety and personalized. That’s getting more attraction. Take time to achieve that. All of this biotech will be continue booming and need a lot of newcomers. A lot of funding to support it. For industrial, any company, you have to think of the direction. Most importantly, how quickly can you support yourself, not totally rely on fundraising.

You can get a product, put it on the market, and start to generate enough blood to support yourself. That’s the key. With that, you can last longer. Otherwise, this is for all the startups. There’s this calling three years of failures called Test Trap. If you pause that, that’s something to keep in mind, and this field needs more brave people and continues to go.

You make some great points in there. It sounds a little bit of the focus of DiaCarta, which is that whole process, the diagnostic to therapeutic. I like the term personal medicine. People are taking that into their own hands, and the industry is developing next-level technology and treatments, allowing them to do that to be able to take advantage of that and prevention.

The market is crazy now, the amount of people that we need and the shortage in terms of basically in the biotech industry. What compounds that is that in this industry, you need scientists and medical professionals. You need business professionals that have experience and understand the process of managing clinical operations and everything that goes into it.

I recruit professionally as my career. I work with biotech pharmaceutical companies. I have conversations with hiring managers all the time. It’s an acute issue we have now. Hopefully, over time, it will even out if we can get more people educated in that area and be able to get them out into the field. I appreciate you coming on. Thank you for telling us about DiaCarta. You’ve got an interesting product there that is being applied across a couple of different areas. Congrats to you, and thank you.

Thank you. I appreciate your time, Ammon.

 

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About Adam Zhang

BTI 45 | Translational GenomicsDr. Zhang is an active entrepreneur and executive in the biotech and pharmaceutical industries with extensive experience ranging from startups to major corporations, including Panomics, Affymetrix, and Bio-Rad. Dr. Zhang brings knowledge and an extensive network in Asia and Emerging Markets to his role at DiaCarta. His substantial experience in R&D management and capability building in Asia and Emerging Markets has a project scope ranging from discovery research to sales and marketing in both US and international markets. He received his Ph.D. from Simon Fraser University in molecular toxicology and pharmacology, was a postdoctoral scholar at the University of Massachusetts, and served as an assistant professor of research at the University of California, Berkeley. Dr. Zhang has published many research papers in leading scientific journals. His inventions are the subject of many patents and patent-pending applications.