Collaborative Chip-Technology Startup Looks to Make Gene Therapy Affordable & Accessible

At the cutting edge of chip technology, startup Mekonos is tackling the bottlenecks and accessibility of gene editing with a view of significantly decreasing the cost of access to cures and treatments of genetic diseases and improving life for millions. We sat down with Steven Banerjee, CEO of Mekonos, to find out more about chip technology, gene therapies, and their power-packed team.

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Tell us a bit about your background and your co-founders.

I’m a visiting scholar at UC Berkeley’s Global Founders Program who founded Mekonos after realizing that my academic and graduate work in New Zealand wouldn’t go anywhere without a multidisciplinary team. I met my co-founder, Anil Narasimha, at Stanford and our other co-founder, Greg Sitters, in New Zealand. We’ve assembled a team of engineers, scientists, and business minds to apply chip technology to gene therapy. Within the team, we’ve got multiple PhDs in engineering and biology, material scientists, and biomedical engineers, and a brilliant business mind. We are also architecting an incredible scientific advisory board, with world leading scientists.

Before we dive in, give us a quick update on industry progression and where things are today.

Today, we have the capability to read the book of life: the human genome using DNA sequencing. For the last 15-20 years or so, we have been able to look at a person’s DNA and sequence a genome with fairly reasonable accuracy, find out what mutations a person has in their DNA, what “errors” have occurred, and describe characteristic traits about a person at the most fundamental genetic level. In the past, the problem was that we could see where a mutation had occurred, we knew there was a problem and a repair that needed to be made, but we couldn’t fix it – we couldn’t ‘write to the genome,’ to use engineering language.

Thankfully, we’ve progressed and gene therapy exists today. Gene therapy is when you edit a person’s genes: you genetically engineer a cell, repair the defect in the DNA structure so that you can tackle genetic disorders such as lymphatic disorders, different types of cancers including leukemia, hemophilia, immune deficiency disorders, cystic fibrosis, etc. The problem is that such breakthrough gene therapy drugs are outrageously expensive and thus inaccessible to the vast majority of the world’s population.

How does gene therapy or gene editing work? What’s the typical ‘production process’ or ‘manufacturing process?’

Let me tell you a specific scenario, wherein you take cells from a patient – let’s say a patient who has leukemia or hemophilia – then you sequence their DNA to pinpoint which part of the genome sequence is causing the disorder. You create a new DNA sequence that, when delivered, will correct the error.

Now, you can’t just insert new DNA into a patient with a needle – it’s not that simple. You need a carrier, a vehicle of transport back into the patient’s body. The technical term is a vector, and the gold standard right now is using a virus, such as a flu virus or an HIV virus, that has been disabled. A viral vector is a carrier of this new DNA sequence: you put this virus carrying the repaired DNA back into the patient’s body. The virus finds a cell as it normally would, it goes into the nucleus of the cell, then corrects the error with the new DNA sequence using the cell’s internal machinery. You’re correcting a mutation and permanently fixing for a disease: that’s gene therapy.

Using a virus as a vector to achieve gene therapy has a lot of issues, however: safety risks, manufacturing problems, and scaling problems, namely. Gene therapy isn’t a traditional drug or cure; a lot of these will potentially be a one-time cure for one person, it’s per patient. For every patient you have, you have to go through this long and resource-heavy manufacturing process. Imagine the number of experts and professionals required to generate a gene therapy for one patient…between the man-power and the inputs, it’s no wonder that producing gene therapy is incredible expensive.

What problem are you currently tackling?

We want to remove the biological and chemical vectors (carriers) from gene therapies and replace them with an engineered technology, with an assembly line of chips. We want to make gene therapy safer and scalable: if it’s scalable, then there are economies of scale, which means it also becomes more accessible and eventually affordable. When you have an accessible solution for potentially 6,000 to 10,000 genetic disorders that are out there, you’re tackling the life and health of a lot of people in this world - it’s remarkable!

How are you applying technology to the medical field? How are you disrupting an industry?

We are a chip technology company, not a diagnostic, drug, or medtech company. We’re using microfluidics and semiconductor technology to deliver corrected DNA sequences directly into cells to correct mutations and thus permanently fixing a genetic disorder. Basically, what Intel did for the computer industry creating micro-processor architecture, we’re doing for the gene therapy and medical industry.

Last year, the FDA approved the first gene therapy drug in the US and the first gene therapy drug in Europe was approved in 2012. Europe’s Glybera costs $1.4 million per patient because of its complex manufacturing process which takes weeks or months (potentially several years if the drug company acquires clinical grade viruses from third party manufacturers). Though Glybera was taken off the market in 2016, it’s manufacturing process had complex biological and chemical protocols as well as expensive inputs – vectors or virus carriers are not cheap. In fact, such protocols, along with the manufacturing of the vectors, can cumulatively contribute to almost 40-50% (possibly higher) of your gene therapy drug COGS (cost of goods sold, basically your variable costs).

We anticipate that we are likely going to reduce COGS by 70-75%, reduce turnaround time to 24-48 hours, and bring gene therapy directly to patient or point-of-care to make them accessible. We’re eliminating biological and chemical vectors, along with a number of related intermediary steps such as purification and multiple complex quality control protocols. In doing so, we’re shrinking the entire gene therapy operation and workflow, removing bottlenecks that currently exist. We’re fundamentally removing a lot of clutter from the workflow, thereby streamlining it.

Mekonos is developing a machine that requires two input parameters for each patient: isolated cells of interest that need to be corrected, turning them into living drugs; and the payload with the designed and corrected DNA sequence. We are designing our system to have individual, disposable cartridges with an assembly line of these silicon chips. These chips carry the designed payload for a patient and use tiny needles, nanoneedles all individually moving, to inject the payload into the isolated cells. Afterwards, you have genetically engineered cells that, following some quality control steps, go back into the patient’s body for specific therapeutic impact. Thus, you’ve potentially fixed the genetic disorder permanently.

What are some of the biggest challenges you’ve faced and how have you overcome them?

We’ve found that a lot of Silicon Valley investors are weary of funding high-risk, high-reward blue-sky projects and technology-in-progress developments. Thankfully, events such as the first FDA approval of a gene therapy drug to Novartis last year, the CRISPR revolution (pioneered by Berkeley’s Jennifer Doudna and team) have put gene therapies on the map: they will end up potentially curing a large number of genetic disorders which makes our company relevant and vital, thus more attractive for investment because startups are also about timing, not just risk. But it still remains a challenge to get funding for a longer-term high-impact project.

The other challenge is cutting-edge resources. When you’re talking about cutting edge technologies, you need multimillion-dollar world-class resources. For example, we found out about a phenomenal program with Lawrence Berkeley National Labs where if your proposal gets accepted, they grant you access to their resources for free, including multi-million dollar equipment - it’s phenomenal! The challenge remains though, to continuously get access to high-end resources while trying to run your organization.

Finally, there are technical challenges of scaling up our system. We’re going from modifying hundreds and thousands of cells to billions. It’s more of an engineering challenge than a biological one: it’s deterministic, so we can use clever design to overcome such engineering challenges.

What’s your roadmap for the future?

We’re planning to do a Series A next year and Series B by end of 2020, but our motivation is simple: we want to contribute to the read-write future of the genome. We want to contribute and eventually make therapies affordable and accessible to mainstream society and bring them to patient point-of-care places.

Meanwhile, we continue to work on our chip technology with nanoneedles and writing to the genome with surgical needle precision. We’re pushing to develop a machine with cartridges and chips so that they can be readily available in hospitals, cancer centers, and more.

Who have been your key partners in this venture?

Novartis, one of our seed investors following the last financing round has endowed us with a lot of biospace in their Emeryville research facility. Obviously Lawrence Berkeley National Labs and their facilities. Then Stanford University has helped tremendously with the research they’re doing and co-owning technology. We’re doing a couple of proof-of-concept trials with Stanford on certain types of bone marrow transplants in mice. Another is MD Anderson Cancer Center – we’re working with them on t-cell therapy for solid tumors. Obviously, we’re talking to a lot of drug companies as well as major chip manufacturers.

What resources within the UC system have been beneficial to you and why?

Berkeley’s Marvell Nanofabrication Lab has been a huge resource, as has the Berkeley Biomolecular Nanotechnology Center – we’re an industrial user. But it’s not just about labs. One of our principal scientists is from Berkeley and some members of technical staff are Berkeley recruit and they’re just tremendous.

Our lead investor actually found out about us because we were part of a SkyDeck co-hort. We also won second place in the LAUNCH competition in 2017.

We’ve benefited from access, staff, and exposure thanks to UC. I have to say, without UC Berkeley and Stanford, Mekonos wouldn’t exist.

Any patents in process?

Yes, we have filed three family of patents and we’re expecting to file another 3-4 family of patents within the next six months. Then even more beyond that!

What advice would you give to fellow entrepreneurs?

One of the things I’ve learned is you should always start a company thinking about customers: who will your customers be? We’ve talked to tons of experts, hundreds in industry, hundreds of customers, and along the journey, for me personally, how I see customers has changed: they’re no longer an abstract notion. As I’ve continued to engage with the industry and specifically with customers (drug companies, medical centers, hospitals), what I realize is that there are real people with emotions and feelings behind the concept of customers. What is the value you’re bringing to their personal life, their life as a human being? When you start talking about that, they’ll see you as value, not as a threat. So keep your customer in front of you at all times: how can you change their lives? That kind of thinking transfers to how can you create a product that will change their lives. We’re so wrapped up in creating a great technology that we forget our customers and how they feel about using your product. We can’t forget the customer, they are key.

 

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