Category: BioPharma

Cayuga Biotech is a preclinical therapeutics company whose lead compound, CAY001, shows promise to change the way that severe bleeding episodes are treated. We spoke with CEO Damien Kudela, who explained the science and path forward for Cayuga.

Watch and read an abbreviated version of the conversation below.

How did you transition from academia to biotech entrepreneur?

I had never envisioned an academic route for my career and by the time I was done, I was looking for a new way to apply my scientific knowledge. Cayuga was seeded by a conversation I had in my 4th year of my Ph.D., where someone said that there was a real need for this technology and I should think about creating a company to advance it. Since we’d already been in the early stages of patenting my thesis and the CAY001 drug, I figured ‘I’ve already been a starving grad student; why not go be a starving entrepreneur as well?’

How do platelets work with polyphosphate to promote clotting, and where does CAY001 fit in?

If you think of a clot as a brick-and-mortar material, the platelets form the bricks. There’s a second compound called fibrinogen which is the mortar. That constitutes the physical clot. 

The problem becomes how to get that brick wall to plug the wound. Polyphosphate is produced by platelets and is essentially a catalyst for clot formation, a molecule whose job it is to speed things up. Adding polyphosphate helps the clot to form more quickly, which enables the clot to shut off the bleeding more quickly.

Bleeding causes a lot of negative outcomes for patients, so stopping the bleeding has many benefits. Not only are you saving their lives by reducing blood loss, but you can actually reduce the time it takes for them to heal as well. 

Bleeding causes a lot of negative outcomes for patients, so stopping the bleeding has many benefits. Not only are you saving their lives by reducing blood loss, but you can actually reduce the time it takes for them to heal as well. 

How does CAY001 differ from other pro-clotting drugs available?

Typically, many currently available drugs are recombinant factors that are either direct mimics of endogenous proteins or slight alterations of these same proteins. 

The issue with bleeding and clotting is that they are two sides of a seesaw. Typically, a patient is balanced flat but when they get injured, and start bleeding, the seesaw tips toward the dangerous effects of too much bleeding. Unfortunately, what can happen with recombinant drugs is that the balance remains out of whack; they can tip the seesaw in the other direction and they can have the dangerous effects of what’s called ‘throwing clots.’ 

This is a huge problem. All the drugs that treat bleeding currently have a black box label warning because of that. And doctors have to weigh a crucial decision in treating patients, asking whether the patient is critical enough to warrant the safety risk.

Using polyphosphate as a catalyst differs from these drugs because it has an effect on the rate, but it doesn’t affect the specific clotting factors present. For example, polyphosphate has its biggest effect on the clotting factor, thrombin. The patient doesn’t produce more thrombin. Polyphosphate has a more limited effect, so you can hopefully use it in a safer way.

What data support your hypothesis?

We’ve been looking at different tissues, specifically the lungs. This seems to be where a lot of nano-based drugs fail. Obviously, the liver is also a concern, because it plays such a huge role in clotting. And of course, the blood-brain barrier. 

What we’ve done is compared CAY001 to saline in a pig model. Pigs are hyper-clotters, so there was some evidence of clotting, but it was the same in both the saline and CAY001 drug-treated animals. That was likely the results of the pigs’ natural clotting cascade, but obviously, safety is the number one concern, especially in this field. The first question we’re always asked is, “is it safe?”

“Is it effective” is always the second question. We’re on the pathways and have very promising data that we’ve seen so far to lead us through safety, and the remaining IND-enabling studies as well as our clinical trials.

What will your clinical trials focus on for the first indication?

Until IndieBio, we were fully funded by DARPA and the Army. Obviously, bleeding is a huge problem on the battlefield and causes about 50% of deaths. There’s also a huge problem with bleeding here in the U.S., especially as patients age and may need to be prescribed anti-clotting drugs such as plavix or coumadin. The problem is that these patients are already in the clotting phase; they’re given anti-clotting drugs and they go back to a risk of bleeding. A lot of it is done because there is no treatment for bleeding.

There are other conditions where patients may benefit from a drug like CAY001. We’ve been focusing recently on platelet dysfunction. This could also benefit patients on chemotherapy who end up with thrombocytopenia, as well as patients who have congenital platelet disorders. We’ve identified a hemophilia-like genetic disease that affect platelets, as opposed to Factors 8 or 9. There’s a wide range of people who may benefit.

Obviously, everybody thinks the quantity of life is a major benefit, because bleeding can kill very quickly. Stopping a bleed also importantly enables patients to have a better quality of life, so they don’t have to worry about shaving or having an accident, whether the kitchen will be fatal. You can really help to give patients their life back.

Who is the Cayuga Biotech team?

I was at UC Santa Barbara, and the sole graduate student who really did any animal experiment at UC Santa Barbara was Kyle Ploetze. Kyle actually has a very good story of the first time we med; I’ll let him tell it another time. I ended up working with Kyle to test our new drug, and we hit it off while doing the test. The data worked well, and we got along well. Kyle and I jokingly refer to CAY001 as kind of our baby.

We were the two initial co-founders; in 2019, we needed to add a third person to do a lot of our quality controls. We were working on our manufacturing, and Nate, a postdoc at UC Santa Barbara, interviewed and we thought he was excellent, so brought him on board. It’s been excellent working together.

What are the next major milestones for Cayuga on the road ahead?

We had our first meeting with the FDA in May 2020, so we’ve gotten feedback. What we really need to do is finish our PK/PD and tox studies. These will help to figure how the drug is cleared and its toxicity; are there any adverse effects from the drug, what doses are safe, what doses are effective. Really, we need to determine it’s safe enough to move to human trials. We’re excited to present our data at Demo Day.

Learn more about Cayuga Biotech and all of IndieBio New York Class 1 companies at Demo Day.

Beeline takes engineered immune cell therapy in a new direction. They are unique in how they have engineered regulatory T cells (Tregs), which play a natural role in ramping down the immune system. This has wide applications for autoimmune diseases and organ transplantation.

We talked with company founders Dimitre Simeonov and Michael Wyman.

Since you’ve announced that you’ve successfully engineered Tregs, you’ve had a good number of pharma companies wanting to partner with you. How did you accomplish something they couldn’t do on their own?

A number of companies have learned how to edit the genome of effector T cells, such as killer T cells. The idea of doing similar genetic engineering of Tregs was beginning to be considered. But actually doing it was another story.

To start with, Tregs are just hard to cultivate and proliferate. Then, there were a lot of hurdles to overcome in terms of the genetic engineering. We weren’t just engineering a receptor into the Tregs to localize them to the spot of inflammation. We wanted to go beyond that — to enhance the natural immunosuppressive power of Tregs. This meant delivering a very large genetic payload to a precise spot, without interrupting the normal function of the gene we were targeting. We found unique ways to pull this off.

How do they work, and what’s the benefit of a “living drug”?

Tregs naturally quiet the immune system. They do this through a unique cellular programming that relies on transcription factors, cell surface receptors, and cytokines that help a Treg shutdown other immune cells. Sometimes this process fails as Tregs can be overwhelmed by the immune response. So we supercharge them and put them back into a patient’s bloodstream, so they can migrate to inflammation hotspots, where they can secrete therapeutic proteins to calm an immune response.

As a “living drug”, Tregs have unique advantages over standard molecular therapies. First, we can harness the cell’s ability to produce protein to continuously manufacture therapeutic proteins in the body. And not just anywhere — but precisely at the site that needs the therapy. No more biweekly injections — just a single shot of your own cells. Second, cells can “sense” their environment and respond accordingly by changing gene expression. By engineering our therapies into the “responder genes” our cells will make therapeutic proteins in response to the environment that those cells are in. For example, say we are trying to quell inflammation as in the case of Crohn’s disease — we might engineer our therapeutic so that its expression is increased in an inflammatory environment thereby allowing us to precisely control dose and ensure we are delivering the highest doses to the areas of the body that need them. Finally, cells are complex machines armed with a number of “tools” that allow them to accomplish their functions. This is fundamentally different from the medicines that have so far dominated the clinic — generally drugging a single target or pathway.

Our technique solves a problem that every drug company is challenged with. How to get the drug exactly where you need it, and maintain a dose potency that is appropriate to the severity of the disease.

It’s like having a drug factory in your body.

Yes, though we’re technically not secreting synthetic drugs. We can do that (as long as they are protein-based), but at this point, our cells secrete the natural signalling compounds the body already makes and uses on its own. We’re the first therapeutics company to publicly announce that we’ve made the proteins we’re making from Tregs; it’s very exciting.

Why did you use DNA-cutting enzymes instead of the more conventional viral vectors?

We actually are doing both approaches. With the viral approach, we do get a high expression rate, but it comes at a tradeoff. The virus lands randomly on a cell’s DNA. You can’t control where the virus integrates the payload. And when it integrates, it can disrupt gene function, which might be a pretty important gene. Also, every gene has a different expression level. So in one cell, you might randomly hit an area of the DNA that is highly acvtive, and in another cell, you could hit an inactive area. You end up with different levels of the therapeutic in each cell — or worse some of the cells may not express the therapeutic because the surrounding inactive DNA could spread to your therapeutic.

To get a much more controlled result, we are also using non-viral engineering approaches. This overcomes many of challenges we mentioned earlier and allows us to think about how to use a cell’s natural gene regulation to regulate our therapy.

In what critical indications is your cell therapy most needed?

Helping the transplantation of organs is where physicians are the most excited by what we’ve done. Today, to prevent rejection of a donated kidney, physicians have to give patients a lot of broad systemic immunosuppressants. These patients are already in a weakened state, and having no immune activity is dangerous. Also the drugs make the patient very vulnerable to cancer; one of the most common drugs is classified as a Group 1 carcinogen. There are a lot of patients who don’t even get put on the waiting list for a kidney, because they are too high risk.

By localizing the immune suppression, and helping patients’ immune system not reject a donor organ, we can open the door to new types of transplants that aren’t very feasible yet. One of those is pancreatic islet cells; they produce hormones. People with Type I diabetes could be alleviated with islet transplantation.

One of the exciting potentials of this therapy is long term tolerance — meaning patients could potentially come off of immunosuppressants all together. This is something we are actively working towards.

What’s the next year look like for Beeline Therapeutics?

We have the ability to engineer receptors to help the Tregs home to the right places in the body — over the next year we’re going to expand that platform with more receptors. A kidney donor has to match the patient’s HLA markers. We’ll use the patient’s HLA markers to design receptors to recruit Tregs into the donor tissue.

Also, proving our method works in mice presents an interesting challenge, because we engineer human T-regs, but a mouse’s immune system would attack human cells. The elegant way to solve this is to use a mouse model without any immune system, repopulate it with a human immune system, and then transplant the mouse with human tissue, to see if we can prevent rejection.

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

In the last two decades oncology has seen a revolution as treatment transitions to targeted genetic drugs. Yet each therapy relies on a specific genetic profile, limiting the number of diseases it can target. Filtricine is taking a unique approach to treating cancer, targeting changes in cancer cell metabolism rather than genetics. Their approach aims to provide a side-effect free approach to treating a broad range of cancers which all share these metabolic weaknesses.

I chatted with Xiyan Li, co-founder and CEO of Filtricine about his origins and the company’s mission to revolutionize oncology.

Can you tell us a bit about how you became interested in the science of metabolism?

I’m a trained biochemist so I always understand biology from the chemical perspective. Basically, I believe that chemistry is the foundation of life. For life, you only needed two things: metabolism as the chemical foundation, alongside intelligence. If you understand the chemical foundation, you will have a really powerful solution to solve a lot of biological problems.

How did you take this theory and turn it into Filtricine?

In the world of cancer, many people are just focusing on what’s wrong in the cancer cell’s genome, what genes are mutated, and how those functions may contribute to this malignancy. It may be easy for people to forget that because cancer cells are so good at evading drugs by quickly evolving new mutations, it’s probably not the best idea or best strategy to treat them with drugs that are targeting one form of a gene function. My co-founder and CTO, Jimmy, and I, we were both working on metabolism where it is very well known that cancer cells have a very distinctive type of metabolism, which we usually call the Warburg effect. We take advantage of this change in cancer metabolism to create a new type of therapy.

Can you tell us about this new therapy that you’re taking forward into preclinical studies?

We are focusing on reprogrammed metabolism in cancer cells. Due to cancer cells rapid growth, they make a critical compromise: they give up the ability to synthesize many nutrients inside in the cell. These cells have to rely on getting those nutrients from the blood, but normal cells aren’t reliant on the supply available in blood as they can synthesize these nutrients within themselves. First, we have to find out what these nutrients are and then figure out how to take just those nutrients out of the blood, then we can achieve killing cancer cells while simultaneously leaving normal cells unharmed.

The actual product we’re making is a fully drug free nutrition deprivation diet and dialysis. We give patients a diet designed to specifically deprive the body of certain nutrients cancer requires, but are not necessary for healthy cells. The second part is a plasma-mimicking dialysate designed to further pull these specific nutrients out of the body.

How do you think this approach, if successful, can change the pharmaceutical industry?

I think that there are two things. First, we are a drug-free therapy, so we do not use any drug content and our products are a solution, a mixture of things known by the body to be non-toxic, so we can quickly customize solutions based on individual requirements. This means that it is totally customizable, yet scalable. Second, we are broad-spectrum. So far, almost all kinds of drugs are developed by targeting just one particular indication, while our products have demonstrated a broad spectrum efficacy, and it’s likely that we are hitting on a universal feature that is underlying this cancer metabolism. This means that we can actually kill a variety of cancers through attacking this common feature.

What are some lessons learned transitioning from a research scientist into being an entrepreneurial scientist here at IndieBio?

We were scientists, not entrepreneurs, before joining IndieBio, so we thought of things very differently than after going through the IndieBio program. As a scientist, you only want to be the first and that is your focus, but as an entrepreneur, you want to be the best. What you want is to figure out and execute a viable solution to make your products that are as good as possible.

What are some important milestones that you’re looking to hit in the near future as a company?

We are currently at the preclinical stage, our aim is to move to human trials as soon as possible.

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

Gene therapy recently has been extremely exciting in the news. However, the limitation of gene therapy is ineffective delivery. When injecting genes to be delivered, especially in adeno-associated virus (AAV), we are seeing an induced immune response where the body starts clearing out the virus. Serenity Bioworks is working to rid the immune response and instead induce a tolerance response, allowing the AAV to be dosed and redosed as necessary.

How did you become interested in immune tolerance?

Cody: The immune system is one of the most complex things in the universe, and that in itself is incredibly interesting. There is a lot yet to figure out. The more we understand about the immune system, the better the development of therapeutics will be able to unlock the next frontier of medicine for monogenic diseases. From a holistic viewpoint, our compounds have been detected in contexts where our own cells and microbiome communicate with the immune system to induce tolerance, as well as other instances where immune tolerance is present. Serenity’s key insight and my own interest in immune tolerance induction came from doing research in this area.

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

Cody: I decided to start the company after I developed my ideas in grad school, which involved applying certain concepts I learned. I decided to raise some money to look at these ideas a little bit more. At the time, I was living with Spencer Berg, my co-founder, and I would come home and talk about what I was up to, certain grants that I’d raised, pitch competitions I’d won. And then he developed an interest as well. Eventually, we got accepted into an incubator in Canada to further develop the technology behind our company.

So how does your technology work? What was that key insight?

Cody: The key insight is understanding how your immune system decides not to attack your microbiome or your own cells. There’s a set of compounds that kept on popping up in these contexts — this is what I was looking at in grad school, though in a different way. We thought that this would be a really good solution for developing tolerance for gene therapy products.

During IndieBio, what lessons have you learned transitioning from scientist to entrepreneur?

Cody: There are so many lessons! For one, you pick up a lot of jargon as a scientist, and you’re used to communicating with scientists. An entrepreneur has to communicate to a broad range of audiences. You might be talking to an accountant, a lawyer, an investor… You will find yourself talking to people who have never heard of your field before. As an entrepreneur, it’s incumbent upon you to properly communicate to a broad range of audiences. You have to lose all of the jargon you pick up in academia and adapt.

And how do you think your success as a company will change the gene therapy industry?

Cody: We are developing an immune-compatible gene therapy. For the last 30 years, gene therapies have been combatting against the immune system. We want to work with the immune system to unlock these therapeutics. If we’re successful we will make these therapeutics safer and more effective.

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

Cody: In the near future? We’re going to wrap up our first set of studies in vivo, raise our next round of financing and conduct IND-enabling studies next year. We’re also looking to develop partnerships with pharmaceutical and gene therapy companies that are running into issues with the immune system.

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

Neurodegeneration is one of the most devastating diseases of aging, and today there is no cure. Stem cells are a very promising way of regenerating the faulty neurons, which would potentially create a cure. Convalesce is working on injecting stem cells into the brain using a special matrix that mimics the brain’s architecture, allowing the stem cells to survive, differentiate. and reconnect those neurons for Parkinson’s patients. We chatted with Subhadeep Das, co-founder and CEO of Convalesce.

How did you become interested in stem cell research?

Subhadeep: When I was a grad student I read a lot about the potential of stem cells in regenerative medicine and I was fascinated by the things stem cell therapies could unlock. Especially so for diseases that cannot be treated using traditional medicine, or are facing certain limitations within current treatment options. Stem cell-based treatment could overcome these drawbacks and limitations, which is how I got interested in the field. It was fascinating for me to work in an interdisciplinary area and not exclusively in hardcore biology or hardcore material science. I started working at the intersections of material science, especially with nanomaterials and stem cells, and when we came up with extracellular matrices which mimic the natural tissue it was a great thing for us from a science perspective. When we found that it could potentially solve some of the very key problems of stem cell therapy for neurodegenerative diseases like Parkinson’s, we eventually came up with a therapy for Parkinson’s disease using our discovery.

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

Subhadeep: I honestly didn’t have any plan of starting a company when I began my Ph.D. At that time I was just interested in doing cutting-edge science, but eventually, when I saw the potential of the technology that we developed, I was saddened to see that academia is happy with just publishing some papers. I wanted to push it further to bring the technology to the clinic where real people would get help out of the technology. During the final years of my Ph.D., I decided to take the leap to become an entrepreneur and try to commercialize this technology. Eventually, I started participating in startup boot camps, business competitions to at least have an idea of how a startups work and what are the non-science aspects that I should think of to start with.

After I got interested in entrepreneurship, I was talking to my friends and acquaintances regarding my ideas. My benchmate from IIT Bombay, Amrutraj, got interested and he had the type of cell biology background that was complementary to the skills that I have. We decided, okay, let’s give it a shot — let’s form a company and see if we can bring this thing together to solve the pending science problems and then bring the technology to the market.

How does your technology work? What was the key insight?

Subhadeep: The fundamental insight for us was to understand how stem cells would react to their microenvironment. Subsequently, we engineered that microenvironment specifically for neurons. It was such an amazing technical insight to learn during the process, now we believe that we have a platform where we can engineer multiple tissue matrices for multiple applications. The key for us was the realization of how crucial a matrix is for regenerative medicine for any organ. Most of the biology research has been focused on cells which, while crucial, as they are will actually do the job, if you consider any organ there are a lot of support systems that play a critical role. These were sort of neglected by biologists and we tried to bridge the gap between material science and biology by engineering specific niches for organs or stem cells. This was the insight for developing what we are currently doing.

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

Subhadeep: We learned a lot of things during IndieBio, especially how to run a business. We always think about science and focus on the next scientific milestones, but after coming to IndieBio, we realized that there are a lot of things we need to have an understanding of if we are to bring this therapy to the market. When we started this was just a science project, not a business. Here we benefitted by getting insights on running a business and developing a business model, an idea of manufacturing, and the regulatory hurdles that are coming for us. I’d say these are critical to running a business.

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

Subhadeep: The traditional therapeutic industry works by generating drugs from small molecules, but there is a whole emerging industry focusing on regenerative medicine which encompasses both stem cell therapy and gene therapy. Even in the cell therapy space most of the companies are still focused on cell type because that’s what comes to a biologist’s mind first: how to engineer the cells and get them to work more efficiently. We are radically changing that approach by engineering not only cells but also their microenvironment. If cells get a much better environment to survive and differentiate in, then they can finally do the job they are sent in to do. I think the holistic approach that we are creating will change the way therapies are done today, the microenvironment is critical for cell-based therapies to be successful.

What milestones are in the near future?

Subhadeep: We aspire to apply our first therapy, which is a stem cell therapy for Parkinson’s, in a human brain. We want to treat Parkinson’s patients as soon as possible. Our key milestone is to do our first human trials so that we know we have a cure for Parkinson’s.

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

Over 600,000 people suffer from slow and difficult to heal bone fractures within the U.S. every year. These ‘non-union’ fractures are common in people with low and imbalanced hormones, such as the elderly, but may also result from infection, inadequate blood supply to the bone, and incorrect splinting. Surgery, which has a low level of success, is the current standard of care. Full recovery from non-union fracture surgery is rare and repeat surgeries are often required.

MezoMax created a first of its kind, convenient, twice daily oral formulation called MMX that works by delivering calcium directly to the bone producing cells to accelerate healing and provide for more complete bone union in non-union fractures. We asked the founder and President of MezoMax, Dmitriy Rybin, PhD., about his discovery and subsequent founding of the company:

How did you become interested in science?

DR: Science is really a tool to better structure and simplify ideas; it is also a means to channel one’s innate curiosity. I’ve always been curious about the variety of the world. My curiosity about our world is diverse, ranging from not only physics and science, but also includes non-scientific exploration. However, it is my scientific training that has allowed me to simplify and connect common principles based upon these experiences.

When did you decide to start a company, and where did your team get together?

DR: My team and I decided to officially start our company a year ago, but this is actually the result of a five year collaboration between my colleagues here in the US and in Russia. I have often thought about starting a company during my 30-year journey in science with my co-founder Dr. Girgoriy Konygin. Our shared work at the Russian Academy of Sciences has been rewarding and is the basis for our company.

How does your technology work?

DR: Our technical approach is based upon fundamental principles of solid-state chemistry reactions that take place under external mechanical loads. Sometimes although the chemical composition of a drug remains unchanged, the molecular crystal is transformed into a new state with unique physical and chemical properties, including a significant increase in biochemical activity. Using this approach, it is possible to obtain new pharmaceutical forms that may not otherwise be possible using traditional methods of fine chemical synthesis or which might otherwise be too expensive to produce.

What lessons did you learn transitioning from science to entrepreneurship at IndieBio?

DR: Entrepreneurship is a very practical, applied endeavor. An entrepreneur needs to quickly figure out who needs our product, and this became much more important to me when I started thinking like an entrepreneur. It seems rather simple, but it’s not. It’s a pretty big mindset shift. More over, it’s necessary to talk about our product in simple and clear language, and not to use ‘science speak.’ Customers need to understand what our product is and why it’s important to them. Learning to make the extraordinary and complicated be understandable, while still keep it exciting, is no small feat! We could not have adapted to this new way of thinking and articulating our value proposition as quickly as we did without the steadfast support and constant counsel of the IndieBio team. We are and will continue to be grateful for their expert advice.

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

DR: On the surface, what we do appears to be so simple! In reality, what we’ve done is to create a new and important platform for drug creation, one which is based upon solid-state mechanochemical synthesis. This approach can be used to create new pharmaceutics that were not previously possible or that were too expensive to produce. As such, we believe our approach will continue to be an important basis for much of the future for creating new pharmaceutical treatments.

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

DR: MezoMax intends to introduce our first compound, MMX, to the US in 2022 for treatment of non-union fractures. Given the extensive clinical safety and efficacy data, we are pursuing an abbreviated approval process based upon the expert advice of four independent regulatory experts. Therefore, one of our first important milestones will be for us will be to meet with the FDA to confirm this viability of our regulatory strategy by March 2019 with the intent of filing our IND by July 2019. We expect to receive our NDA early in 2022, leading to our subsequent product launch.

Watch MexoMax pitch on IndieBio Demo Day, Tuesday April 17th in San Francisco or via LiveStream. Register here!

Traditionally, people in pain are given Opioids—which, although they relieve pain, can have dangerous side effects such as loss of motor function, and addiction. Ocycontin, Vicodin, and other pain relievers are effective in subduing pain, but they are extremely addictive, which causes major problems in families and communities.

The Opioid Crisis is a reality we’re facing now—but what if pain could be treated another way? That’s exactly what Neurocarrus has been working on. Their new drug delivery technology safely disrupts pain signals without possessing addiction-forming qualities. We asked the company’s CEO, Benjamin Pavlik, more about how this works:

How did you become interested in biotech?

BP: After having reconstructive surgery on my knee in college, replacement of ligaments and anchoring with bio-diffusible and titanium screws allowed me to run again. It was an amazing success, but difficult. This experience changed my life in many ways, and I became interested in working on technology that would be useful for others experiencing similar procedures.

When did you decide to start a company, and where did your team get together?

BP:  My former PhD advisor and I decided to start a company at the University of Nebraska, Lincoln when we realized the incredible potential for this technology.

How does your technology work?

BP: Neurocarrus has developed an injectable non-opioid pain drug called N-001. N-001 is a novel protein that was synthesized to target key sensory neuron structures called actin. It is designed to disrupt peripheral pain signaling without affecting motor function or causing addiction.

What lessons did you learn transitioning from science to entrepreneurship at IndieBio?

BP: Transitioning from science to entrepreneurship is challenging but rewarding. The communication skill set is different, and it takes time to learn and adjust. Once technical terms are replaced or simplified, sharing science with our greater society enables the research to reach a broader audience to learn and benefit.

How do you think your success as a company would change the healthcare industry?

BP: Our success as a company would change the healthcare industry by providing an alternative to opioids as a front-line pain management solution. This would give millions of Americans who live with pain a less difficult choice and in turn reduce substance abuse.

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

BP: We are aiming to test N-001 in an advanced animal pain model. A positive preclinical outcome would support clinical trials.

Watch Neurocarrus pitch on IndieBio Demo Day, Tuesday April 17th in San Francisco or via LiveStream. Register here!

Science is catching up with cancer. We are in a new era of personalized medicine for diagnosing and treating patients, now zooming in even closer, on an individual’s genome. By understanding the genetic causes of cancer, and measuring the differences between someone’s cells that are affected by cancer with the ones that are not, Onconetics can leverage the regulatory network of the cells and create a trigger for a kill gene that only activates within cancer cells. We asked Gabe Hitchcock, the company’s COO and co-founder, some questions about how this all works:

How did you become interested in biotech?

GH: Luke and I became interested in biotech through our own channels, him through his father at UCSF and me through my own undergraduate research in neuropharmacology. Though we had different beginnings, our journeys led us to the same question: how do we make better drugs for patients? Luke and I strongly believe that the key to better treatment lies in the patient’s own genes.

When did you decide to start a company, and where did your team get together?

GH: After months of deliberation, we started the company in the fall of 2016. For the first six months of the company, I was finishing up my B.S. at Oberlin College in Ohio, so I would fly out of Cleveland on weekends to meet Luke in San Francisco, Washington D..C, or New York as we built the company and our network.

How does your technology work?

GH: Our technology is predicated on the understanding that genetics determine the advent and progression of cancer. The hypothesis was simple: what if we could use these unique biomarkers not only to diagnose cancer, but also to guide the development of our drug? In essence, to create a drug that works only within the genetic environment of our choice. This is exactly what we have done at IndieBio: we have engineered a drug that selectively kills cancer cells without impacting healthy tissue. We call this approach Genomics-Informed Drug Design and we see it as the future of medicine.

What lessons did you learn transitioning from science to entrepreneurship at IndieBio?

GH: Science is a highly iterative process. Ideally, one experiment tells you one thing that informs the next experiment… and on and on and on. When we first started out as entrepreneurs, we applied the same approach. We absorbed all the feedback we could in one go, went back to the lab and restructured, then did it again. However, the same perfectionist approach used in R&D does not always bear fruit in entrepreneurship. It’s easy to get lost in the details and caught in a cycle of endless restructuring. IndieBio helped us hone in on what really mattered: our story, our community, and getting out there. In a sentence, IndieBio helped us get out of the lab and into the Valley.

How do you think your success as a company would change the medical industry?

GH: There’s no point hiding it: what we’re doing is entirely new and disruptive. The success of our company will cause a fundamental shift in the way the medical community treats patients. We’re not screening a single molecule against 1,000 cell lines to see what sticks, nor are we tweaking a chemical a 1,000 different ways to best block a pathway. What we are doing is engineering a drug from the ground up to target cancer. In 15 years, Genomics-Informed Drug Design will be the standard of medical treatment.

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

GH: In the near term we are planning on transitioning into our own lab space in the Bay Area, making key hires, and moving our therapy closer to IND. Because we are taking a bioengineering approach to medicine, there is also a lot of optimization that needs to be done. This means long hours in the lab, but each new experiment brings us that much closer to the ultimate goal: an accessible, scalable cure for cancer.

Watch Onconetics pitch on IndieBio Demo Day, Tuesday, April 17th in San Francisco or via LiveStream. Register here!

Cancer cells have defense mechanisms that can cause chemotherapy and other standard cancer treatments to become increasingly difficult for a patient to endure, as stronger drugs are often needed after the cancer cells adapt. Instead of killing cancer cells with stronger drugs, Nivien has a found a way to break down the defense mechanisms of cancer cells by first watching their response to drugs, and then designing small molecules that act against the specific defense mechanisms that the cancer cells are observed to be using. For this reason, Forbes recently called Nivien’s technology “The Trojan Horse of Cancer Treatment”. Nivien’s approach will allow existing drugs to become more effective. We asked the company’s co-founders, Nikita Shah and Nathaniel Brooks Horwitz, a few questions:

How did you become interested in biotech?

Nikita comes from a clinical perspective, preparing for medical school, working as an EMT, and shadowing oncologists. She also built a better preclinical model for testing small molecules (the same class of drug that Nivien is developing) in a biomedical research lab at Massachusetts General Hospital. Nathaniel worked in three biomedical research labs (Boston Children’s, Harvard Stem Cell Institute, Harvard Medical School) and at RA Capital, a biotech venture capital firm. We came together around a shared passion for translating important biomedical research into new medicines for patients.

When did you decide to start a company, and where did your team get together?

We began Nivien under the mentorship of Dr. Derrick Rossi, the scientific founder of Moderna. We decided to start the company when key academic discoveries converged around the importance of our target in cancer resistance. After raising initial venture funding, we recruited Dr. Ken Fang, a principal scientist from Allergan, and Dr. Dharmendra Singh, a veteran cancer biologist from UCLA, Houston Methodist and the NIH.

How does your technology work?

Rather than directly killing cancer cells, Nivien targets the shields that protect cancer from existing treatments. Nivien develops small molecules that inactivate the first upstream regulator of many proteins responsible for the failure of dozens of FDA-approved cancer treatments. We will combine Nivien molecules with existing drugs to create a better reformulated product that has higher effectiveness and lower side effects than current options.

What lessons did you learn transitioning from science to entrepreneurship at IndieBio?

We learned that science moves much faster at companies than in academia. We also learned to focus on doing “the killer experiment” at each step to prove or disprove a theory as quickly as possible, rather than spending time and money on auxiliary experiments that provide support but not clear answers.

How do you think your success as a company would change the medical industry?

Our mission is to dramatically improve the standard-of-care in cancer therapeutics.

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

We are filing key patents, establishing partnerships and hiring new team members to fill critical roles moving forward.

Watch Nivien Therapeutics pitch on IndieBio Demo Day, Tuesday, April 17th in San Francisco or via LiveStream. Register here!

Photo credit: IndieBio