How A 60-Year-Old Drug Developer Built A $4.4 Billion Biotech Treating ‘Butterfly Skin Disease'

Forbes

2 days ago

L ongtime drug developer Suma Krishnan was in her late-40s when she had the idea for a topical gene therapy to treat a rare and terrible skin disorder in which the skin becomes as fragile as butterfly wings. In 2016, at 51, after a few months of modeling the idea and starting the process of patenting it, she and her husband Krish Krishnan, with whom she'd worked in biotech for more than a decade, cofounded Krystal Biotech.
Focusing on a rare disease, with just thousands of patients in the U.S., was unusual. So, too, was shunning venture capital in favor of self-funding a biotech startup, with some $5 million they'd made mainly from previous biotech companies. But perhaps the biggest bet was the science, taking a completely new approach to a problem with a gene therapy delivered as a gel that would potentially pay off big if it succeeded, but also stood a high chance of failure. 'I had to work with the regulators because they had never seen this,' Krishnan told Forbes . 'It was completely new.'
Just 18 months after launching the Pittsburgh-based company, the Krishnans took it public on the Nasdaq stock exchange. Today, Krystal has a market cap of $4.4 billion with one FDA-approved therapy, Vyjuvek, for that "butterfly skin disease,"called dystrophic epidermolysis bullosa, on the market, and other gene therapies, including for cystic fibrosis and lung cancer, in various stages of clinical development. All rely on the modified herpes simplex virus, but they have different delivery mechanisms. The company's revenue reached $291 million for 2024, up more than five-fold from $51 million in 2023. Net income surged eightfold to $89 million from $11 million in the same period.
The Krishnans have a combined 12% stake in the business. Suma, the company's president of research and development, is worth some $300 million by Forbes estimates, almost entirely from her stake in the business and sales of stock over the years. Krystal's stock has been volatile: It's up more than 1,300% since the IPO, but has fallen nearly 25% over the past year.
'You have to be brave and bold to do this,' Krishnan says. 'I was never afraid of risk-taking. I never felt like I needed a stable job.'
Krishnan is one of the 200 entrepreneurs and leaders on this year's Forbes' 50 Over 50 list. These women—who this year also include actress Halle Berry, on the list for her menopause-related startup; social mission-oriented investor Freada Kapor Klein; and Maria Shriver, who founded the Women's Alzheimer's Movement toward the end of her first term as first lady of California—are all generating outsized professional impact in their sixth, seventh or eighth decades.
Suma Krishnan, who is now 60, grew up in Bombay where her parents struggled to raise three kids. As the middle child and a girl, Krishnan says, her mother, who married at 18, began looking for arranged marriages for her as soon as she finished college. She refused. 'I always defied it and fought it,' she says. 'I was a tough one for them. I broke all the rules.'
She came to the U.S. for graduate school, getting a master's degree in organic chemistry at Villanova University. (While there, she met Krish Krishnan, who was getting his MBA at Wharton and lived nearby.) After that, she worked as a drug developer, starting at Janssen Pharmaceuticals. At New River Pharmaceuticals, she led the discovery, development and approval of Vyvanse, a blockbuster drug to treat ADHD. After European drugmaker Shire (acquired by Takeda for $62 billion in 2018) bought New River for $2.6 billion in 2007, she worked on rare diseases. Then, at Intrexon (now known as Precigen), she focused on gene therapy treatments as its head of therapeutics. She holds more than 70 patents for a variety of drugs. 'For 25, 30 years, this is all that I did,' she says. 'I am familiar with all kinds of rare diseases and where the unmet need is.'
'I was never afraid of risk-taking. I never felt like I needed a stable job.' Krystal Biotech cofounder Suma Krishnan
She had an idea for a gene therapy for butterfly skin patients that could be delivered as a gel directly onto the affected skin using a modified version of the herpes simplex virus to deliver the treatment. The drug works by delivering a healthy copy of the gene that encodes a type of collagen to the skin cells, enabling healing to occur. Some 25,000 people in the United States have epidermolysis bullosa, but only around 3,000 of them have the dystrophic form of it, which is severe and for which Krystal's treatment is used.
Brett Kopelan, executive director of Debra, a nonprofit for those affected by the disease, and whose daughter, now 17, was born with a severe form of it, calls it 'the worst f—-ing disease you've never heard of.' Kids with it often live with constant pain and need to be bandaged on much of their bodies; they're also susceptible to numerous other ailments, including a form of skin cancer. 'My goal is to make this a chronic, livable disease like type 2 diabetes,' says Kopelan, whose daughter uses Krystal's treatment, among others. 'We're getting really close to that, and we have Suma and Krish to thank.'
When she had the idea that became Vyjuvek, there were no treatments on the market. While she was at Intrexon, that company had been working with another biotech, Fibrocell (which has since been purchased by Castle Creek), on a hospital-based therapy. 'I saw the pain and suffering,' Krishnan says. 'These kids are born with missing skin from birth and it gets worse over time. They say, 'Nobody cares about us.''
She took the idea to her husband Krish, who had been the chief operating officer at New River and Intrexon and with whom she had worked for well over a decade. They decided to develop the drug—this time on their own. Biotech was booming and lab space was impossible to find in San Francisco. Instead, they searched the country for locations, settling up in a vacant lab space in Pittsburgh, a city known more for robotics startups than biotech but where they could hire grad students from Carnegie Mellon, at first flying back and forth from their home in northern California. They shunned VC funding, raising a small amount from friends and family and telling them bluntly to think of their investment as philanthropy. 'We figured if it didn't work out, we'd shut it down,' Krishnan says.
In 2017, they took the company public, raising $45 million, thanks to Krish Krishnan's network taking previous companies through their IPOs. 'It was a Mickey Mouse IPO,' he says, noting that it allowed an investor from Fidelity who'd backed his previous companies to become a shareholder. 50 Over 50: 2025 Our fifth annual list of 200 women who are redefining what's possible in life's second half. VIEW THE FULL LIST
The idea of delivering gene therapy at home rather than in the hospital was both elegant and a little crazy. 'Look, honestly, as great as the idea was, when somebody comes and says, 'I want to put gene therapy in a gel on a wound at home,' it's like somebody saying today, 'I want to have a house on Mars,'' says Krish Krishnan, the company's CEO. 'Yeah, great idea, but how are you going to get there? It was that kind of idea.'
Six years later, in 2023, Krystal received FDA approval for Vyjuvek—very fast for a novel gene therapy. Getting the FDA to sign off on a home-based gene therapy that would use a modified version of the herpes virus during the Covid-19 pandemic required studies that could allay any concerns about safety at a time when, as Krishnan notes, 'people were very nervous about viruses.'
They set a list price of $24,250 per vial. That works out to an annual cost of $631,000 per year for an average patient who uses 26 vials, before discounts; but patients typically require fewer treatments over time as their wounds heal. Gene therapies tend to be expensive, with many costing $1 million or more. With rare disease, 'the payers are a bit more forgiving on the pricing,' Krish Krishnan says, noting that any one insurer is unlikely to have more than a few patients with the disease. 'We can show the value proposition to Blue Cross Blue Shield and they understand,' he says.
Life sciences investor Dan Janney, managing partner of Alta Partners, was among the few friends who invested personally in Krystal in the early days, having met Suma and Krish through their children, who went to school together. He calls Krystal 'probably the most efficient company that I've ever been involved in' in terms of its use of capital. 'They've done a really incredible job of getting to profitability,' he says.
'As great as the idea was, when somebody comes and says, 'I want to put gene therapy in a gel on a wound at home,' it's like somebody saying today, 'I want to have a house on Mars.' Krystal Biotech cofounder Krish Krishnan
Krystal's drug for the butterfly skin disease isn't the only one on the market anymore. In April, clinical-stage biotech Abeona Therapeutics (which is publicly traded with a market cap of $348 million) gained FDA approval 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. That treatment, which has a list price of $3.1 million, launched this summer.
Having gotten the one therapy on the market in the U.S. and approval for it in Europe and Japan, Krishnan is now looking at other diseases in lung disease, cancer and eye ailments. One of the furthest along, now in phase 3 clinical studies, is for ocular complications of the skin disease they're already treating. Others, now in earlier stage clinical trials, include treatments for cystic fibrosis and for lung tumors, a particular focus of Krishnan's given the increasing prevalence of lung cancer among younger women who never smoked. In each case, Krystal's drug would deliver a healthy copy of the gene to treat the disease, though the delivery mechanisms vary, with the lung cancer therapy using a nebulizer, for example.
The big question is whether Krystal can successfully expand beyond one rare disease to multiple drugs that can treat a variety of health problems using gene therapies delivered with the modified herpes virus. Krishnan's plan is to use the cash from Vyjuvek's commercial sales to fund the clinical development of those other therapies. 'We have money and we can use that to develop the rest of our pipeline products,' she says. 'The first one is always harder.'
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