Krystal Biotech, founded by Krish & Suma Krishnan, is a clinical-stage gene therapy company focused on developing and commercialising re-dosable, off-the-shelf genetic medicines for the treatment of severe, life-threatening or rare diseases that have limited or no approved therapies..
Krish, what was the original vision behind Krystal Biotech?
The founding idea came from my wife, Suma , who leads R&D. We’ve worked together for 20 years in startup biotech and both had prior experiences with dystrophic epidermolysis bullosa (DEB). Suma came up with a conceptually simple, elegant idea to fundamentally correct the disease. That idea germinated in early 2016, and we made our own investment to get it off the ground, building a lab and a team to see if this could become a proof of concept.
From 2016 onward, one thing led to another: proof of concept, going public, early clinical trials, and ultimately getting Vyjuvek for DEB approved in 2023.
Since Vyjuvek’s approval and rollout, what has the launch reinforced for you about delivering real patient impact?
Innovation only matters if it reaches the people who need it and changes their lives fundamentally – that’s the true value of an idea.
DEB patients have a difficult life, not just the patients but the whole family, because their skin can wound with any type of friction, with constant pain and having to keep the wounds bandaged.
When Vyjuvek was approved, it was transformational not only because it fundamentally treats the disease, but because it’s convenient. Not requiring patients to travel, having treatment delivered to them at-home and applying a gel to a wound in a painless way mattered enormously. It has been adopted well in the U.S., Europe, and now Japan, and the most important part to date has been safety—unlike many gene therapy stories where you quickly hear about safety concerns, which have been non-existent with Vyjuvek so far.
About how many patients suffer from DEB globally?
There are about 3,000 patients in the United States, with roughly 1,200 diagnosed. In the U.S., one reason for misdiagnosis or lack of diagnosis is that genetic testing isn’t that prevalent or paid for by insurance, so many patients go without a confirmed diagnosis.
There are about 3,000 patients in Europe, but most are genetically tested and confirmed. Outside the U.S. and Europe, there are roughly another 3,000. In total, that’s about 9,000 to 10,000 patients globally, split somewhat equally between the U.S., Europe, and the rest of the world.
You’ve described Vyjuvek as a “fundamentally corrective” treatment. Can you explain, in practical terms, how it works at the genetic level and what that means for patients?
DEB is monogenic disease, caused by a mutation or missing gene called COL7A1. What Vyjuvek does is provide a clean copy of the gene to the patient. It doesn’t try to fix the broken gene; it delivers a clean copy of DNA into the nucleus.
A big advantage, and part of the safety record, is that we don’t interfere with the patient’s existing DNA. COL7A1 produces anchoring fibrils that hold the skin together. When the gene isn’t working, patients don’t have anchoring fibrils, so the skin falls off. By providing a clean copy, anchoring fibrils form and wounds are healed. The earlier you treat a patient, you see wound closure & skin durability, which positively impacts quality of life, whether that’s being able to travel, be more active, or simply be able to wear clothes that don’t hide their skin.Thankfully, Vyjuvek is approved from birth now.
Are you using the insights from Vyjuvek to treat other diseases as well?
Yes. The same modality applies to other monogenic diseases, with cystic fibrosis (CF) front and center. CF is a mutation in a single gene and we provide lung cells a fresh copy of the gene. we’ve shown proof-of-concept delivery across all lobes of the lung in a simple 10–15 minute administration through a nebulizer.
We also have alpha-1 antitrypsin, again monogenic, as well as neurotrophic keratitis. Across the pipeline, the story is re-dosable gene delivery to the skin, lung, or eye. When the cell that holds the new gene turns over, we re-dose so the new cell, which is mutated, gets a fresh copy of the working gene.
We also have exceptions where we use the same delivery modality for cytokines in lung cancer—IL-2 and IL-12—with the hypothesis of stimulating the immune system and shrinking tumours, and longer term, we want to migrate toward broader genetic material delivery, potentially including antibodies.
As you expand into oncology, where does the lung cancer program currently stand in clinical development, and what near-term readouts should stakeholders look for?
It’s already in Phase 1, and we had a proof-of-concept announcement last year. The study continues to move forward. Recently, the program received RMAT (regenerative medicine advanced therapy), which is essentially “breakthrough” status for biologics; for gene or cell therapy, the FDA calls it RMAT.
RMAT reflects the agency’s view that there is potential and allows close, frequent interaction with the FDA to try to bring the drug to market. Depending on how the data evolves, there is a possibility of accelerated approval in the near future. If not, we would run a full randomised pivotal trial. The early data looks promising, but it’s early and has to be realised over time.
As programs mature, have you considered changing your approach to manufacturing?
Unlike bespoke modalities, we are off the shelf—scientifically, not autologous but allogeneic. In gene and cell therapy, we think it’s critical to control manufacturing because quality is essential when dealing with patients’ genes, and trade secrets matter.
We invested heavily into manufacturing early, before we knew the drug would be approved. We have two facilities in Pittsburgh where we make the drug to ship globally. We believe manufacturing should be a core strategy, and we don’t plan to change that as we get bigger. If anything, we want to scale manufacturing beyond the U.S..
Looking at the next 12 months, what excites you most and what are your priorities?
Getting Vyjuvek to patients across the world and hearing stories about lives changing, not just from the U.S. but from Japan and Europe, remains heartwarming and a major focus..
We’re in two pivotal trials right now, one for neurotrophic keratitis and another for lesions in the eye from DEB, which received the FDA’s platform technology designation, . The priority is positive pivotal readouts and getting ready to bring these therapies to patients worldwide. We also have other programs that could enter pivotal trials later this year, making it a very busy commercial and clinical year.
