Key Concepts
- Topical gene therapy
- Epidermolysis Bullosa (EB)
- Collagen 7
- Anchoring fibrils
- Herpes simplex virus (HSV) vector
- FDA approval process
- Venture capital vs. self-funding
- Initial Public Offering (IPO)
- Cystic Fibrosis (CF)
- CFTR gene
- Nebulized drug delivery
Suma Krishnan's Journey and Crystal Biotech's Founding
Suma Krishnan, co-founder and president of Crystal Biotech, discusses her journey from a lab scientist to developing a novel topical gene therapy for Epidermolysis Bullosa (EB). She started her career in big pharma companies like Pfizer and Johnson & Johnson, focusing on drug development, moving products from molecular hits to clinical studies and regulatory pathways. However, she felt pigeonholed and lacked the ownership and comprehensive involvement she desired.
Krishnan realized she wanted to develop drugs for herself, owning the process and the intellectual property. She quit Intrexon, filed an IP for her idea to treat a rare skin disease using a vector to deliver genes, raised friends and family money, and started Crystal Biotech.
Decision to Forego Venture Capital
Crystal Biotech avoided venture capital to maintain control over the company's direction. Krishnan wanted the freedom to pursue her compassionate vision for treating EB, having connected with patients and advocacy groups. Venture capital involvement could have led to strategic shifts, a sale of the company, or a direction misaligned with her passion.
Early Funding and IPO
The company was initially self-funded with investments from friends and family who were aware of the high risk. Krishnan's experience in drug development allowed her to efficiently manage a limited budget and avoid common pitfalls. A small, dedicated team of five to six people conducted the necessary studies for a Phase 1 IND (Investigational New Drug) application.
Strong investors, who had previously profited from Krishnan's ventures, advised taking the company public. Crystal Biotech went public in 2017, just a year and a half after its founding, raising $30-40 million at a valuation of $50-60 million. As of the interview, the company's valuation is $4.4 billion.
Focus and Responsible Growth
Krishnan emphasizes the importance of staying focused and responsible with investor money. Crystal Biotech avoided unnecessary expenses, such as large offices, and prioritized in-house work. Krishnan personally wrote investigational documents and protocols, trained her team, and mentored young scientists.
Epidermolysis Bullosa (EB) and Topical Gene Therapy
EB is a rare genetic disease affecting an estimated 2,000-4,000 people in the US and 30,000 globally. It is caused by a defect in the collagen 7 gene, which results in the lack of functional collagen 7 protein. Collagen 7 is crucial for anchoring the epidermis (top layer of skin) to the dermis (layer below), forming anchoring fibrils. Without collagen 7, the skin layers slide over each other, leading to severe blistering and open wounds from minor friction.
Crystal Biotech's gene therapy involves a topically applied gel containing a modified herpes simplex virus (HSV) vector. The virus is engineered to be non-infectious and carries the human collagen 7 gene. When applied to open wounds, the vector delivers the gene to skin cells, enabling them to produce collagen 7 and correct the skin defect.
FDA Approval Process
The FDA approval process for the topical gene therapy was challenging because it was a novel approach. Crystal Biotech worked closely with the agency to determine the clinical pathway, administration pathway, clinical study design, and endpoints. The COVID-19 pandemic added further complexity. A key consideration was enabling at-home administration of the weekly treatment, as patients could not travel to a clinic regularly.
Potential Applications Beyond EB
The HSV vector used in the EB therapy has potential applications for other diseases, including lung diseases, cancer, and eye disorders. Crystal Biotech is exploring these possibilities and has a pipeline of clinical trials for multiple indications.
Cystic Fibrosis (CF) Program
Crystal Biotech has a program for cystic fibrosis, a rare disease with a subset of patients who do not produce any CFTR protein due to a specific mutation. The company is developing a nebulized formulation of the HSV vector carrying the CFTR gene. Patients can inhale the nebulized vector, delivering the gene directly to their lungs and enabling CFTR protein production. The program is in Phase 1/2 clinical trials, with early safety data showing promise.
Advantages of Experience
Krishnan believes that being over 50 is both an advantage and a disadvantage. While aging presents challenges, her passion and perspective gained from seeing patients suffer provide motivation. She emphasizes the importance of focus, responsibility, and avoiding unnecessary expenses.
Advice for Young Women
Krishnan advises young women to be humble, learn as much as possible, and leave their ego at the door. She stresses the importance of patience, hard work, and endurance. It took her 25 years to gain the experience and knowledge needed to start her own company and develop a successful therapy. She encourages young women to be honest about what they know and don't know, and to be willing to do even mundane tasks.
Notable Quotes
- "The day when pain stops is when I know I'm dead." - EB patient, highlighting the constant suffering.
- "I'm like a dog with a bone. I knew that I have this product and I I need to take it to the finish line." - Suma Krishnan, emphasizing her focus and determination.
- "Knowledge is your weapon." - Suma Krishnan, stressing the importance of continuous learning.
Synthesis/Conclusion
Suma Krishnan's story is one of perseverance, compassion, and strategic decision-making. Her journey from a lab scientist to the founder of a multi-billion dollar biotech company highlights the importance of ownership, focus, and a deep understanding of drug development. Her decision to forego venture capital allowed her to maintain control and pursue her vision for treating EB patients. The success of Crystal Biotech's topical gene therapy and its potential applications for other diseases demonstrate the power of innovation and a patient-centric approach. Krishnan's advice to young women emphasizes the value of humility, continuous learning, and patience in achieving long-term goals.
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