The drug developer Add Krishnan was just over 50 years old when he had the idea of topical gene therapy to treat a rare and severe skin disease in which the skin becomes as fragile as the wings of a butterfly. In 2016, at 51, after a few months of modeling the idea and starting the patent process, she and her husband Krish Krishnan, with whom she had worked in biotechnology for more than a decade, co -founded Krystal Biotech.
Focusing on a rare disease, with only thousands of patients in the US, it was unusual. It was also possible to avoid risk capital in favor of self -financed biotechnological startup, with about 5 million dollars that had mainly obtained from previous biotechnological companies. But perhaps the biggest bet was science: adopting a completely new approach to a problem with a gene therapy administered in gel that would potentially be very profitable if it succeeded, but also had a high probability of failure. “I had to work with the regulators because they had never seen this,” Krishnan said Forbes . “It was completely new.”
Only 18 months after the launch of the company based in Pittsburgh, the Krishnan took it with the Nasdaq. Currently, Krystal has a stock market capitalization of 4,400 million dollars and has a therapy approved by the FDA, Vyjuvek, for distributing ampoup epidermolysis (butterfly skin disease), and other gene therapies, such as cystic fibrosis and lung cancer, in various stages of clinical development. All are based on the modified herpes virus, but their administration mechanisms are different. The company’s revenues reached 291 million dollars in 2024, more than the 51 million dollars of 2023. Net revenues multiplied by eight, to 89 million dollars, compared to 11 million dollars in the same period.
The Krishnan have a joint participation of 12% in the company. Sum, President of Research and Development of the Company, has a assets of about 300 million dollars, according to estimates forbes coming almost in its entirety of its participation in the company and the sale of shares over the years. Krystal’s shares have shown volatility: more than 1300% have risen since their IPO, but almost 25% have fallen in the last year.
“You have to be brave and bold to do this,” says Krishnan. “I was never afraid of taking risks. I never felt the need for stable work.”
Krishnan is one of the 200 entrepreneurs and leaders who appear on the list Forbes 50 Over 50 of this year. These women – among those who are also actress Halle Berry, included in the list by her startup related to menopause; the investment with social mission fry Kapor Klein; and Maria Shriver, who founded the Movement of Women with Alzheimer’s towards the end of her first mandate as the first lady of California – are generating a huge professional impact on their sixth, seventh or eighth decades of life.
Add Krishnan, who is now 60 years old, grew up in Bombay, where his parents struggled to raise their three children. As a medium and wife daughter, Krishnan tells that her mother, who married at 18, began looking for concerted marriages for her as soon as the university ended. She refused. “I always challenged him and fought,” he says. “I was a difficult person for them. I broke all the rules.”
He arrived at the US to perform a postgraduate degree and obtain a master’s degree in organic chemistry at the University of Villanova. (During his stay there, he met Krish Krishnan, who was in Wharton and lived nearby). After that, she worked as a drug developer, starting at Janssen Pharmaceuticals. In New River Pharmaceuticals, he led Vyvanse’s discovery, development and approval, a great success to treat ADHD. After the European Pharmaceutics Shire (acquired by Takeda for 62 billion dollars in 2018) bought New River for 2600 million dollars in 2007, worked on rare diseases. Then, in Intrexon (now known as Precigen), he focused on gene therapy treatments as head of therapy. It has more than 70 patents for a variety of drugs. “For 25 or 30 years, this was all I did,” he says. “I am familiar with all kinds of rare diseases and where the needs are not met.”
I was never afraid to take a risk. I never felt the need for stable work.
Suma Krishnnan, Crystal of Krystal Biotch
He came up with an idea for gene therapy for patients with butterfly skin. This therapy could be administered in gel directly on the affected skin, using a modified version of the Simple Herpes virus. The drug acts by managing a healthy copy of the gene that encodes a type of collagen to skin cells, which allows healing. About 25,000 people in the United States suffer ampollosa epidermolysis, but only about 3,000 have the distribution form, which is serious and for which Krystal treatment is used.
Brett Kopelan, Executive Director of Debra, a non -profit organization for people affected by the disease, and whose daughter, now 17 years old, was born with a serious form of it, calls her “the worst illness you have ever heard.” Children who suffer usually live with constant pain and need bandages in much of the body; They are also susceptible to many other ailments, including a type of skin cancer. “My goal is to turn it into a chronic and bearable disease, such as type 2 diabetes,” says Kopelan, whose daughter uses Krystal treatment, among others. “We are very close to achieving it, and we have to thank Sum and Krish.”
When he had the idea that became Vyjuvek, there were no market treatments. While working in Intrexon, that company collaborated with another biotechnological company, Fibroell (which was later acquired by Castle Creek), in a hospital therapy. “I saw pain and suffering,” says Krishnan. “These children are born without skin and the situation worsens over time. They say: ‘No one cares for us.”
She introduced her husband Krish’s idea, who had been director of Operations of New River and Intrexon, with whom she had worked for more than a decade. They decided to develop the drug, this time on their own. Biotechnology was booming and it was impossible to find laboratory space in San Francisco. On the other hand, they looked for locations throughout the country and settled in a vacant laboratory space in Pittsburgh, a city known more for robotics startups than by biotechnology, but where they could hire Postgraduate students of Carnegie Mellon, at first traveling round trip from their home in northern California. They avoided risk capital financing, raising a small number of friends and family and telling them without surroundings that will consider their investment as philanthropy. “We think if it didn’t work, we would cancel it,” says Krishnan.
In 2017, they took the company, raising 45 million dollars thanks to the Krish Krishnan contact network, which guided previous companies through their departures. “It was an IPO of Mickey Mouse,” he says, noting that he allowed a Fidelity investor, who had supported his previous companies, became a shareholder.
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How a 60 -year -old drug developer created a biotechnological company of 4,400 MDD to treat ‘butterfly skin disease’
The idea of managing gene therapy at home instead of the hospital was both elegant and a bit crazy. “Look, sincerely, no matter how great the idea was, when someone comes and says: ‘I want to apply gene therapy in gel on a home wound’, it is as if someone said today: ‘I want to have a house on Mars’,” says Krish Krishnan, executive director of the company. “Yes, a great idea, but how is it going to be achieved? It was that kind of idea.”
Six years later, in 2023, Krystal received the approval of the FDA for Vyjuvek, a very fast decision for novel gene therapy. Get the FDA approved a homemade gene therapy that would use a modified version of the herpes virus during the Covid-19 pandemic required studies that dispel any concern about security at a time when, as Krishnan points out, “people were very nervous about viruses.”
They set a list price of $ 24,250 per road. This is equivalent to an annual cost of $ 631,000 for an average patient that uses 26 roads, before applying discounts; However, patients usually require less treatments over time as their wounds heal. Genic therapies tend to be expensive, and many cost $ 1 million or more. In the case of rare diseases, “insurers are a bit more flexible with prices,” says Krish Krishnan, pointing out that it is unlikely that a single insurer has more than a few patients with the disease. “We can show the value proposal to Blue Cross Blue Shield and they will understand it,” he says.
The investor in Life Sciences, Dan Janney, director of Alta Partners, was one of the few friends who personally invested in Krystal in the beginning, after meeting Sum and Krish through their children, who went together to school. Janney describes Krystal as “probably the most efficient company in which I have worked” regarding the use of capital. “They have done incredible job to achieve profitability,” he says.
“As great that it was the idea, when someone comes and says: ‘I want to apply genetic therapy in a gel on a home wound’, it is as if someone said today: ‘I want to have a house on Mars’.” Krish Krishnan, co -founder of Krystal Biotech
Krystal’s medication for atopic dermatitis is no longer the only one available in the market. In April, the Biotechnological company in the Abeona Therapeutics clinical phase (which is quoted with a market capitalization of 348 million dollars) obtained the approval of the FDA for its own gene therapy, called Zevaskyn, which uses skin grafts from sheets of a genetically modified version of the patient’s own skin cells. This treatment, with a sale price of 3.1 million dollars, was launched this summer.
After obtaining the only therapy available in the US market and its approval in Europe and Japan, Krishnan now investigates other diseases, such as lung diseases, cancer and eye conditions. One of the most advanced studies, now in phase 3, addresses the eye complications of the skin disease they already treat. Others, now in initial stages of clinical trials, include treatments for cystic fibrosis and pulmonary tumors, a particular Krishnan approach given the growing prevalence of lung cancer among young women who have never smoked. In each case, the Krystal drug would administer a healthy copy of the gene to treat the disease, although the administration mechanisms vary; For example, lung cancer therapy uses a nebulizer.
The big question is whether Krystal can successfully expand beyond a rare disease to multiple medications that can treat various health problems through gene therapies administered with the herpes virus modified. Krishnan’s plan is to use Vyjuvek’s commercial sales money to finance the clinical development of these other therapies. “We have money and we can use it to develop the rest of our developing products,” he says. “The first is always more difficult.”
This article was originally strength by Forbes Us.
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