Category: Industrial

The CRISPR Cas complex has been a game-changing technology for gene editing. CASPR Biotech is using the incredible accuracy of CRISPR for something different — to revolutionize medical diagnostics.

We spoke with company founders Franco Goytia and Carla Giménez.

There are a couple other prominent companies also using CRISPR-Cas systems for diagnostics. What’s different about your focus?

We are rapidly developing a device for hospitals to quickly detect if a patient has an antimicrobial resistant infection. This is a huge problem for hospitals. It’s not just that 2 million people in the US every year get infected with superbugs, or that the infection rates are even higher internationally. When a patient walks into the hospital with a fever of unknown origin, it takes between 24 hours and three days to amplify the DNA of the bacteria to determine if the patient has AMR. During that time, the patient has to be isolated, making it very stressful and expensive. For every one patient found to have AMR, nine more have to go through this isolation. And during that time, they’re started on wide-spectrum antibiotics, which makes the global problem worse.

How does your solution change that?

We can diagnose AMR infections in under an hour. Most superbugs have one of three sequences of DNA that make them resistant. We code our Guide RNA to detect those, and if they do, our Cas enzymes trigger a signal. Not only does it do so in under an hour, but does so more accurately, and cheaper.

You already have this working?

Yes, in the lab. As well, at a hospital in Argentina we have tested our system to detect infectious diseases like Dengue virus. These aren’t yet automated into a device, but our device development is going incredibly well and we are on track to begin a 510K study with the FDA in one year.

You discovered two novel Cas enzymes, one in the Cas 9 family, one in the Cas 12 family. How did you do that, and how they are different?

Existing IP portfolios held by the primary CRISPR institutions were discovered by searching through the public databases of sequenced bacteria. We went through unpublished data, collected by our partners in the extreme environments of Argentina — regions as diverse as volcanos, high deserts, hot springs, and Antarctica. In these environments, bacteria evolved unique ways of defending themselves against viruses.

We are looking at ways our Cas 12 gives us a competitive advantage. It appears to be more stable at higher temperatures, likely due to the environment where it evolved. Using it at higher temperatures may facilitate other reactions in our system, turning what’s a two-step process into a one-step process.

You’ve been able to make incredibly fast progress during your time at IndieBio. What’s been your secret?

Before IndieBio, we were running on a very thin budget. To order reagents, we might be waiting a few months until we could get the money together. At IndieBio, we got them in a day — and shouted in celebration when they arrived. We showed up at IndieBio really hungry to do science at a much faster pace, to make quick decisions. It’s been an opportunity that we’ve been thankful for, and haven’t taken a single moment for granted.

We’ve also been very inspired by the scientists who created the foundational technologies of CRISPR. The way bacteria has defended itself against viruses has existed for hundreds of millions of years. But it took great imagination to reconfigure it for gene editing. This precedent reminds us, daily, that if we work hard, at any moment we too could make more discoveries.

How big could CRISPR-based diagnostics get?

Certainly, from AMR and infectious diseases we will move into flu detection, respiratory infections, sepsis, and urinary tract infections. But the application go beyond healthcare and the hospital. Just like Google allows us to search the entire internet, CRISPR allows us to search the entire genome for any genetic code. Rapid DNA detection has applications beyond humans into pets, livestock, and plant life. Farming, biosecurity, and new domains of agriculture are all possible.

Watch CASPR Biotech pitch on IndieBio Demo Day, Tuesday June 25th in San Francisco or via LiveStream. Register here!

The successful treatment of cancer lies in early detection. If we can detect it as early as Phase 1 and 2, the outcomes for therapy are significantly better. Unfortunately, symptoms oftentimes will not present until Phase 3 and 4 which limits effectivity of therapeutic interventions. Clinicai is making a noninvasive monitor for colorectal cancer with a device that hooks on the side of your toilet. We asked Chun-Hao Huang, co-founder and CEO of Clinicai, about his journey as an entrepreneur.

How did you become interested in the early detection of colorectal cancer?

Chun-Hao: During my Ph.D. I built animal models mimicking human colon disease to find biomarkers and therapeutics. I was passionate about gastrointestinal biology and learned how to monitor mice’s poop every day, dissect the intestine and colon for pathology examination, and realized that, wow, the stool is actually very closely related to our gut system. I also realized that for colorectal cancer, if we can detect early, we can even use current treatments to cure this disease and every single patient would have the chance to survive.

I have now been working in cancer treatment for more than 10 years and have seen that the field puts a lot of effort into trying to develop new therapeutics. However, a lot of diseases, especially colorectal cancer, can be solved even right now if you detect it in time. But the early detection or preventative angles are not so appreciated by the field. So that’s why I started to focus on early detection because I believe the way to actually make cancer manageable today is by monitoring your body to capture the signals at the very outset so we can apply current therapies when they would be most effective.

How did you decide to start the company and how did your team come together?

Chun-Hao: I almost was a scientist for life, and I really wanted to make a big science discovery creating a way to solve cancers. When I was at the Lindau Nobel Laureate Meeting, I heard a lot of top scientists and Nobel laureates talking about the future of medicine and how to manage diseases like cancer. The meeting inspired me but I realized it is actually a very long process from research to benefiting humanity, and I started to wonder if there is a way we can speed up this process and bring biotechnology into our daily lives.

So I asked what is the best way we can accelerate scientific discovery and also bring biotech to our daily life? It’s very interesting to me that the device we use daily is a cell phone when biotech should be the technology we are using every day. I found the answer is to start a company because you can put a lot of resources into building a product actually related to daily life. I met my co-founders Medina Baitemirova, Juan Carlos Guáqueta, and Mr. Toilet Jack Sim at Singularity in NASA Ames, and later on our CTO Dr. Ya-Ju Lin. We all have different expertise, but we share the same vision that we want to detect disease like cancer early. We wanted to make the most comfortable diagnostic platform, which in the end ended up being a toilet. We want to make people actually enjoy health monitoring.

How does your technology work? What is that key insight?

Chun-Hao: It’s pretty interesting, when we started developing this technology we hoped to achieve three things. First thing, if we want to do the most comfortable monitoring and diagnostic at home, then the technology needs to be non-invasive where the user puts in the minimum effort to maximize regular monitoring. Second is digital information; we need to have a technology which can digitalize the substance we detected. Third, it needs to continuously gather the data. The most current methodology, like biomarkers or chemical methods, are not able to do that, so we started testing a bunch of different sensors. We started with a narrow range optical sensor and in the end, we find out that there is a large wavelength hyperspectral imaging originated from space technology that can help us to gather all the information from the stool.

That’s how we started using that technology to check stool samples and that’s how our technology derived. This is not just technology we can use in the lab, or in the hospital, we actually integrated that into a prototype device that will snap on a toilet. Everyone can attach that device at home, I even tried it myself. Then it can turn on when you sit on the toilet and then gather the data. I think these will be pretty powerful in the future, not only for cancer detection but also can help detect other preventable diseases.

What lessons did you learn transitioning from scientist to entrepreneur at IndieBio?

Chun-Hao: As a scientist, every day you go to a lab, you have the experiment you want to do, but some experiments could take a couple weeks or even longer. But when you are designing your experimental plans in a startup environment, like IndieBio, you need to think about how we can leverage different resources to make this process faster. That’s actually what I really like about this environment because you’re still doing the very cool science, but you have a way to speed it up. The other thing which is quite important is that here we’re thinking of how we can actually turn our technology into a real product and then benefit people’s lives. As a scientist in the lab, you try to solve problems, but you don’t usually think that this can actually work in our daily life.Since we joined IndieBio, we have started to talk to the FDA, we talked to insurance companies, we talked to doctors, and especially to the users. We are building things they really want and also doing cool science. This is what makes being a scientist-entrepreneur great.

How do you think your success as a company will change the diagnostics industry?

Chun-Hao: I used a proteomics approach when I was in college to identify biomarkers and in the past 10 years I didn’t see that many biomarkers come into the diagnostic field. I think it’s time that we need something new to disrupt this field. Before we always relied on one or two biomarkers, but at Clinicai we believe the key is to detect signatures or patterns of the disease.

That’s why at Clinicai we are trying to get signatures and patterns from your stool or urine samples and then we use the machine learning to understand those features. I think that that will change the way we think about diagnosing. The other strong advantage we have is to actually bring the diagnostic into our home. Before it’s been pretty difficult and we find our best niche at home where our bathroom and toilet have a lot of information every day. We hope in the future everyone can really enjoy health monitoring and can live longer and healthier.

What milestones are you aiming to hit in the near future?

Chun-Hao: I want to thank IndieBio because we actually met our milestones here. We’ve built our first prototype, which we never thought about that before. The milestone for next year is to improve our prototype and then work with hospitals to install the device in hospital toilets or in patients’ toilets at home to monitor their stool signals for colorectal cancer detection. After that, we plan to go through the FDA path and we are pretty positive about that. After that, we hope our device will be in everyone’s home for future health monitoring and diagnosis.

Watch Clinicai pitch on IndieBio Demo Day, Tuesday Nov. 6th in San Francisco or via LiveStream. Register here!

Drug delivery is one of the greatest challenges in treating cancer today. There are a multitude of effective drugs that aren’t able to be delivered to tumor sites, or can not be delivered in combination.

Vali Nanomedical is now solving these drug delivery problems with a revolutionary programmable drug delivery system, and working towards a future where in vivo cellular reprogramming can cure disease without even using drugs. I talked with Andrew, Vali’s CEO, about his path to entrepreneurship, its challenges, and the future of Vali. Check out his pitch from IndieBio’s Demo Day Livestream!

AK: Tell me about your background, how did you get interested in the biotech space?

AG: I have PhD in molecular biology, focusing on cancer and developing cancer vaccines as a grad student. I got involved in nanotech knowing that starting a company was the goal. Early on I took a class on entrepreneurship and knew right away that was the path for me, not traditional academia. Going into startups has been really exciting since it’s been a goal for some time.

AK: What problem are you working to solve with your company, Vali?

AG: The biggest issue in cancer is delivering drugs to where they need to be. There are a lot of great drugs out there that can’t reach the right place or are toxic. At Vali Nanomedical, we created a programmable nanoparticle that homes onto cancer cells and releases drugs there but doesn’t harm healthy cells. It’s like making a smart missile that knows when it has missed and refuses to detonate when it’s in the wrong place.

AK: If you could only pick one thing to validate your reason for forming a startup, what would it be? In other words, what would be the single biggest indicator to you that you are doing the right thing?

AG: This is the first time in my entire career that I’ve felt like I’m at home. Every day flies by and is exciting.

AK: How do you think success can change your industry?

AG: We envision a world where drugs aren’t used at all to treat disease. Instead, we’d use our technology to reprogram cells to either return to a healthy state or, if they’re too far gone like cancer cells, reprogrammed to kill themselves. Ultimately we want to make cancer a disease of the past.

AK: How is your team uniquely able to tackle this? What’s the expertise?

AG: We have a fantastic team with very complementary skills. Prof. Mike Wong is a physician-scientist who has dedicated his career to finding better ways to treat cancer. As I mentioned, I’m an expert in the molecular biology of cancer. Prof. Pin Wang is an absurdly accomplished and productive biomedical engineer at USC. The founding team is backed up by industry veterans, including former director of BD at Amgen Holly Hartman and Prof. John Daniels, who literally launched an industry by inventing and commercialized collagen for injection. Between us, we have all the skills necessary to make our grand dream a reality.

AK: Any big lessons learned transitioning from academia to startup entrepreneurship?

AG: You have to reframe the way you talk about your work. Academics are trained to talk about the things they’re 99% sure they’ve figured out. As an entrepreneur, you talk about problems that you haven’t solved yet and demonstrate you have a plan to get there.

AK: What’s the biggest challenge you’ve encountered so far?

AG: Finding the right first addition to the team. It was only by good luck and timing that I found the perfect person to add to the team. He was an amazing materials scientists named Don Johnson, who’s also a PhD.

AK: What are the big goals and milestones you’re looking to hit in the short term? Long term?

AG: Short term are building multiple partnerships with pharma to deliver drugs they can’t deliver now, either alone or in combination to treat cancer. We’re uniquely capable of doing combination therapies. Like I said, in the long term we want to make cancer a disease of the past.
Get in touch with Andrew at andrew.gray@valinano.com