An interview with Karen Aiach, CEO of gene therapy company Lysogene.
By Noah Davis
Karen Aiach. (Photo: Jacques Demarthon/AFP/Getty Images)
In 2005, Karen Aiach’s infant daughter, Ornella, was diagnosed with Sanfilippo Syndrome A, a rare neurodegenerative disease that reduces life expectancy to less than 20 years. After talking to every medical expert she could find, Aiach learned that there was no cure. Instead of watching her daughter slowly slip away, Aiach — an ESSEC Business School graduate who ran a financial consultancy and had no medical background — set out to find one.
Aiach did what she knew how to do. She read. She researched. She started a for-profit company, Lysogene, and raised millions of dollars. She recruited top gene therapy researchers. In 2011, Ornella received her first treatment. But Aiach didn’t stop there.
She and her team believed that the gene therapy technique they used to help Ornella could be applied to many other types of rare and orphan diseases that target the central nervous system. These afflictions, which by definition occur in less than 200,000 people across the United States, include lesser-known conditions like Sanfilippo Syndrome A, but also cystic fibrosis, Lou Gehrig’s disease, and Tourette’s syndrome. Major drug companies stay away from seeking cures because the small population size means that developing treatments isn’t cost-effective.
Many researchers believe that so-called precision medicine — the ability to edit an individual’s genes with the goal of treating their specific malady — is the future of medicine.
Lysogene, which received an orphan drug designation and rare pediatric disease designation from the Food and Drug Administration, is one of the companies leading the way. The company is based in France, but recently opened up an office in Boston. Aiach, who recently gave the keynote address at Harvard University’s Precision Medicine 2016: Rogue Therapeutics conference, spoke to Pacific Standard via Skype from her office in Paris.
What’s new with Lysogene?
We’ve expanded the team, including hiring our new chief technical officer in the U.S. He will be in charge of manufacturing, which is a very critical activity for us. He’ll be based in Cambridge, Massachusetts. He’s the former head of manufacturing at Genzyme. We’ve hired a few product manufacturers here in Paris. We’re working hard on the preparation of a registrational study with LYS-SAF-302, which is our lead product for Sanfilippo syndrome. We’ve had early interactions with the FDA to discuss our plans for LYS-SAF-302. I think we had a very productive discussion with the agency: helping us to put in place the right plans for clinical studies and manufacturing.
How does the process work?
There is a pretty well structured regulatory framework for the orphan drugs. We can submit a pre-IND [Investigational New Drug]. Prior to filing a new drug application, we can send a briefing document to the FDA and organize a meeting with them. We share our positions on critical questions that we have. We ask about their views on our positions. Sometimes they will agree and sometimes they will recommend something else. We had a meeting in July. We went through each question to find the FDA’s thinking. Then we go back and fine-tune our plans.
The motto of many start-ups is something along the lines of Mark Zuckerberg’s “go fast and break stuff.” But, as we’ve seen from the Theranos disaster and other examples, medicine can be very different. How do you balance the need to go fast with the need to be safe, especially when the FDA and other regulatory bodies seem to err on the side of extreme caution, and understandably so?
With respect to the FDA, it’s true that they are mostly on the safe side. That’s understandable. I think that what they realize is the question of the timing. They try to compensate with tools and incentives like breakthrough designations. When you have a product that has shown initial efficacy, you can get a breakthrough designation, which will allow you to have faster reviews. You can have rare pediatric disease designation, which we have for LYS-SAF-302, that will expedite the review in certain circumstances. I guess that they are trying their best.
On my side, there are delays you can’t avoid. That’s science. But when it’s about planning and executing, I think Lysogene is very good at that. That’s probably a differentiating factor. We work on that and leverage it. We translated our initial product from bench to bedside in less than five years. It’s not because we have fewer constraints than others — we have the same constraints. And, on top of that, we had small resources. But we were driven and very much focused on our objective. We were driven to deliver and not to lose time.
Is part of that ability to execute owing to your experience as a businesswoman?
Totally. There is that dimension. Plus, the high-sensitivity of the fact that one day lost for the patient is one day of suffering for the patient and for the family. I am eager, and the team is as well, to deliver more well-being to the patients because I live that on a day-to-day basis.
How’s Ornella today?
She’s doing well. She has made good progress in recent days in terms of walking, but that’s also because I’m hosting a therapist for a short time who is giving her massages every day. That has helped her a lot.
Does Lysogene have other products?
We are working on a second product for another disease. We developed that product in collaboration with the University of Massachusetts. That product works more or less like the product for Sanfilippo syndrome.
What’s the business model? Each disease has such a small number of potential patients.
First of all, because of the specific regulation on orphan drugs in the U.S., Europe, Australia, and Japan, there is a niche in the pharmaceutical market where you will have special prices granted with the aim of helping and encouraging the development. Second, the business model of a company like Lysogene is to learn as much as you can with the first two programs and then expand to other programs. We are currently in discussions with academy groups who we may partner with, again for a rare disease. But if you put products for one rare disease, two rare diseases, three rare diseases, then you end up having a nice portfolio. And also, at some point what we’re doing could be leveraged to other diseases. Today, you wouldn’t have a huge gene therapy performed in Alzheimer’s. It would be very expensive to start with. We have no manufacturing capacities today to produce what we would need. That technology has to be validated in monogenetic indications first. I think analysts like gene therapy companies working on monogenetic diseases.
So the idea is to gain a body of knowledge, and then expand from there?
Yes. It’s less risky because you know what you have to do. You have one defective gene and you replace it. It’s pretty straightforward. Diseases like Alzheimer’s, the factors are much more complex.
What are the differences between running a company in the U.S. versus one in Europe?
There is a big difference, relating to money. In the U.S. we’ll raise more money and have bigger valuations for your companies. That’s fine. In France, we have a small incentive tool called research tax credit, which is absolutely great. If you spend, 100 euros for research, the government will refund you by 30 percent. In both territories, you have very specific economic systems. Both have advantages and drawbacks.
For regulatory aspects, things tend to be more convergent, but it’s not always the case. A company that can make a single clinical trial in both territories is in good shape because it’s not easy to do. We know how to do that. In terms of people, it’s hard to say. If I had to give a high-level description, the people here tend to be very creative. What we love with our American colleagues is that they bring a systematic approach. They have procedures in place. We’ve tried to combine the best of Europe and the U.S. We probably do the same with the problems too, but I haven’t noticed it yet.
Will you raise more money?
We’ll have to look for additional money, probably next year. We don’t know what avenue we’ll take yet, but as the ambitions of the company are growing, we’ll need to have additional funding in place. We don’t know which avenue we’ll take.
Which avenues have you looked into?
As anyone, we’re looking at private opportunities and thinking of a listing at some point. We’ll make the decisions later. We’re not short of cash yet.
What’s the roadmap going forward?
We have a manufacturing campaign going for the next study in Sanfilippo syndrome. We’ve learned a lot from phase one, so we are optimizing the parameters, like the way we are delivering the product into the brain of the patient, the delivery device we are using, and the clinical assessment tools. Meanwhile, we have started a natural history study with four sites in Europe and one site in Brazil in order to get more data on the natural cause of the disease. We have enrolled 16 patients out of 25, which is a very, very good progression. It shows the outreach of Lysogene. Enrolling patients in natural history studies is not always easy, especially if there is a competing therapeutic trial somewhere, which is the case. We have a very high degree of credibility [with] patients and partners. With respect to the second program, we’re progressing our non-clinical trials in order to start an early dialogue with the FDA. The goal is to potentially treat our first patient with our investigational drug in 2018.
This interview has been edited for length and clarity.
