Episode 12: Vertex

🔬✨ From Cystic Fibrosis Breakthroughs to Gene Editing Cures

In this episode of Petri Dish Perspectives: Biotech Unleashed, Manead unpacks how Vertex turned cystic fibrosis from a fatal disease into a treatable condition and why they’re now tackling sickle cell, diabetes, and more with CRISPR and stem cell science.

Discover how visionary chemists, Nobel-winning gene editors, and patient advocates built one of biotech’s most inspiring success stories, proving that deep science and real patient impact can go hand in hand.

Grab your coffee and hit play! 🚀

#Biotech #VertexPharma #CRISPR #GeneEditing #CysticFibrosis #RareDisease #HealthcareInnovation #PetriDishPerspectives #BiotechPodcast

Chapters

• 1:04 Founding Story
• 7:12 Cystic Fibrosis Breakthrough
• 13:55 Sickle Cell, Beta Thalassemia, and T1D
• 19:35 Jeff Leiden, Reshma Kewalramani
• 21:21 Keys to Vertex's Success
• 22:00 What’s Next for Vertex?

Transcript

🎙️ Intro

Hello and welcome to Petri Dish Perspectives: Biotech Unleashed, the podcast where we geek out about science and the companies shaping the future of healthcare. I’m your host, Manead, and I’m a scientist with a PhD background in cancer biology and analytical chemistry. With every episode, my goal is to deliver digestible pieces of information on healthcare companies under 30 mins. 

Today, we’re diving into Vertex Pharmaceuticals, a biotech trailblazer best known for transforming cystic fibrosis from a death sentence into a manageable condition for thousands of patients. But that’s just the beginning. Vertex is now taking on gene editing, sickle cell disease, and Type 1 diabetes with the same vision. And also, if you’re based in Boston or have been to Boston before, this company may be quite familiar. I remember visiting Boston for the first time and loved the location of Vertex HQ.

Quick disclaimer: full credit goes to all original sources cited in the transcript.

Grab your coffee or tea, settle in, and let’s jump right in.

🧬 Segment 1: Origins – From Chemistry Roots to Molecular Targeting

Let’s rewind all the way back to a few decades. Before founding Vertex Pharmaceuticals in 1989, Joshua Boger had already carved out a distinguished career in chemistry and drug development. Born in 1951 in North Carolina, Boger pursued his undergraduate studies at Wesleyan University, where he majored in chemistry and philosophy, a combination that hints at his later interest in challenging the norms of pharmaceutical research.

He then earned his PhD in Chemistry from Harvard University, where he studied under Nobel Laureate E.J. Corey, one of the pioneers of modern synthetic chemistry. At Harvard, Boger sharpened his skills in rational drug design and chemical synthesis, gaining early exposure to the power of theoretical modeling in drug discovery.

Boger went on to spend nearly a decade at Merck & Co., one of the leading pharmaceutical companies in the world. There, he rose to the position of Senior Director of Basic Chemistry, overseeing key programs in antiviral drug development. But even at Merck, he grew increasingly frustrated with the limitations of traditional drug discovery—which often relied on randomly screening large libraries of compounds in hopes of finding a hit. It was slow, inefficient, and lacked mechanistic elegance.

Boger had a radically different vision: what if we could design drugs “on purpose”—starting from the structure of a target protein and building molecules specifically to fit it? This approach, called structure-based drug design, was just beginning to gain traction thanks to advances in X-ray crystallography and molecular modeling.

In 1989, he left Merck and founded Vertex Pharmaceuticals in Cambridge, Massachusetts. His goal was to create the first biotech company built entirely around rational drug design, integrating computational chemistry, structural biology, and medicinal chemistry into a unified engine for precision therapeutics.

One of Vertex’s earliest and most high-stakes challenges was designing inhibitors for HIV protease, a key enzyme the virus uses to replicate. The early 1990s were the height of the HIV/AIDS crisis, and protease inhibitors were emerging as a new class of antivirals that could complement nucleoside reverse transcriptase inhibitors (NRTIs) like AZT.

Boger believed Vertex could make a meaningful impact by using structure-based techniques to design molecules that tightly bound the active site of HIV protease. The target protein’s structure had just been solved, giving researchers a detailed map of the “lock” they needed to build a “key” for.

Vertex scientists applied cutting-edge computational modeling and synthetic chemistry to generate a new class of protease inhibitors. Their lead candidate, VX-478, showed promise but ultimately lost the race to Abbott’s ritonavir (Norvir) and Roche’s saquinavir, which reached the market first.

Still, the project was a success in other ways, it validated Vertex’s model of rational drug design and demonstrated that the company could take on highly complex biological targets. It also attracted talented scientists and investment, fueling the next chapter of drug discovery.

Vertex’s early HIV program put it on the map scientifically, even if it didn’t win the first-to-market prize. And more importantly, it laid the foundation for what would eventually become one of the most successful biotech pipelines in the industry. Then came breakthroughs in hepatitis C and pain, but nothing quite stuck—until cystic fibrosis came into view.

Vertex, Inc. (VERX) had its initial public offering (IPO) in 1991. The shares began trading on the Nasdaq under the ticker symbol VERX. It was $4.63 per share. 

💨 Segment 2: The CF Breakthrough – Turning the Tide

Cystic fibrosis (CF) is a rare genetic disease that affects about 90,000 people worldwide, primarily those of Northern European descent. For decades, CF was considered a childhood death sentence—most patients didn’t live past their teens or early twenties. The disease is caused by mutations in the CFTR gene, which encodes a protein that controls the flow of chloride and water in and out of cells. When this protein malfunctions, it leads to thick, sticky mucus building up in the lungs, pancreas, and other organs—causing chronic lung infections, digestive issues, and progressive organ damage.

By the early 2000s, treatments for CF were mostly supportive: antibiotics for lung infections, chest physiotherapy to loosen mucus, pancreatic enzyme supplements to aid digestion. They treated the symptoms, but not the root cause—the broken CFTR protein.

That’s where Vertex stepped in. In 2000, the Cystic Fibrosis Foundation (CFF) took a bold step: it partnered directly with Vertex and invested tens of millions of dollars to find drugs that would fix the underlying genetic defect. This was one of the first major examples of a disease foundation directly funding biotech R&D, creating a new model for patient-driven drug discovery.

Vertex scientists set out to do something no one had done before—find small molecules that could either “potentiate” the CFTR protein (help it open its ion channel properly) or “correct” its folding and trafficking so it reached the cell surface where it was needed.

Years of research, high-throughput screening, and medicinal chemistry paid off. In 2012, Vertex won FDA approval for Kalydeco (ivacaftor)—a potentiator that dramatically improved chloride transport for patients with the G551D gating mutation, found in about 4–5% of CF patients.

For these patients, Kalydeco was life-changing. Kids who had spent their childhoods in and out of hospitals suddenly saw lung function jump by 10–15 percentage points, gained weight, and spent less time on antibiotics or in the ICU. Parents described it as “a miracle in a bottle”—for the first time, their children could think about college, travel, and careers.

But that was just the beginning. Most CF patients have the F508del mutation, which causes the CFTR protein to misfold and break down before it reaches the cell surface. So Vertex developed correctors to help the protein fold properly and combined them with Kalydeco’s potentiator action.

This led to a pipeline of combination therapies:

• Orkambi (lumacaftor/ivacaftor), approved in 2015 for patients with two copies of F508del.
• Symdeko (tezacaftor/ivacaftor), approved in 2018, with improved tolerability and broader use.
• And the blockbuster Trikafta (elexacaftor/tezacaftor/ivacaftor), approved in 2019. Trikafta combined two correctors plus a potentiator, dramatically expanding treatment eligibility to roughly 90% of all CF patients.

Financially, Trikafta became a huge win —generating over $9 billion in annual revenue—one of the highest-grossing rare disease therapies ever. But more importantly, it became a symbol of what precision medicine can achieve when biotech companies, patient foundations, and cutting-edge science align around a clear target.

Today, Vertex remains the undisputed leader in CF. But they’re not stopping there. They’re pushing deeper into gene editing with CRISPR-based therapies aimed at curing CF altogether, not just treating it. They’re also exploring cell therapies to replace damaged lung tissue and looking at ways to help the small percentage of patients who still don’t benefit from existing drugs.

Vertex’s CF journey is now taught in business schools and biotech circles as a masterclass in patient partnership, precision drug design, and relentless execution—a story that proves that sometimes, a company really can give people decades of life back.

🧬 Segment 3: Expanding the Horizon – Beyond CF

Having dominated cystic fibrosis and secured billions in annual revenue, Vertex knew it couldn’t afford to become a “one-trick pony.” Leadership understood that relying on a single franchise leaves any biotech company vulnerable to expiring patents, shifting science, or market disruption. So they set out to diversify — not by chasing just any pipeline, but by staying true to their core strengths: understanding proteins, rewriting cellular behavior, and executing disciplined clinical development.

🔬 Sickle Cell and Beta Thalassemia — CRISPR Enters the Chat

In 2015, Vertex made a bold bet on what was then still a fledgling technology: CRISPR-Cas9 gene editing. They teamed up with CRISPR Therapeutics, a biotech co-founded by Emmanuelle Charpentier, who, along with Jennifer Doudna, would go on to win the 2020 Nobel Prize in Chemistry for their pioneering work developing CRISPR as a genome editing tool.

The idea was simple but revolutionary: instead of treating the symptoms of genetic blood disorders, fix the underlying genetic code. Vertex and CRISPR Therapeutics targeted sickle cell disease (SCD) and beta thalassemia, both caused by single-point mutations that affect hemoglobin, the protein that carries oxygen in red blood cells. Patients with SCD suffer from debilitating pain crises, organ damage, and shortened life expectancy, while those with beta thalassemia often require lifelong blood transfusions.

Their therapy, exa-cel (brand name: Casgevy), works by harvesting a patient’s own hematopoietic stem cells, editing them ex vivo using CRISPR-Cas9 to reactivate fetal hemoglobin (HbF) production, then reinfusing them. Fetal hemoglobin is naturally silenced after birth, but by turning it back on, patients can bypass the faulty adult hemoglobin that causes disease.

By 2023, Casgevy became the first-ever CRISPR-based therapy to receive regulatory approval, starting with the UK’s MHRA and then quickly following with FDA and EMA approvals in 2024–2025. Early trial results were transformative: patients who once required monthly transfusions or suffered frequent pain crises were living transfusion-free and pain-free — functionally cured.

This milestone wasn’t just historic for Vertex and CRISPR Therapeutics — it marked a turning point for all of genetic medicine. It validated that complex gene editing could be done safely, effectively, and commercially at scale. Vertex leads the global rollout and commercialization, while CRISPR Therapeutics maintains control of manufacturing. Together, they represent a blueprint for next-gen biotech alliances: big enough to push through regulatory hurdles, but nimble enough to keep scientific rigor front and center.

💉 Type 1 Diabetes — Regenerating Insulin from Stem Cells

Vertex’s next frontier? Tackling Type 1 diabetes (T1D) — a lifelong autoimmune disease in which the immune system destroys insulin-producing beta cells in the pancreas. For nearly a century, treatment has relied on daily insulin injections or pumps, but patients still face long-term risks like blindness, kidney failure, and cardiovascular disease.

The turning point came in 2019, when Vertex acquired Semma Therapeutics, a Harvard spinout founded by the late Dr. Douglas Melton, a pioneering stem cell researcher whose own children live with T1D. Semma had developed technology to turn pluripotent stem cells into fully functional, insulin-producing pancreatic beta cells — essentially replacing what the immune system had destroyed.

In 2021, Vertex began clinical trials with VX-880, an infusion-based cell therapy that implants these lab-grown beta cells into the liver, where they can sense glucose and secrete insulin in real time. Early results have been remarkable: some patients have reduced or even eliminated their daily insulin needs — something unheard of since the discovery of insulin in the 1920s.

But challenges remain. Since T1D is an autoimmune disease, implanted cells are still at risk of being attacked by the immune system. So Vertex is working on VX-264, which takes the same lab-grown beta cells and encapsulates them in a protective device, shielding them from immune attack while still allowing glucose and insulin to pass through. If this works, it could deliver a functional cure without the need for lifelong immunosuppressive drugs.

🧪 Segment 4: People who made their mark

Vertex is known not just for its science but for the people behind the science — a company culture that blends rigorous discipline with a genuine sense of mission. Unlike some biotechs that jump from one trendy target to another, Vertex is famously clinical trial–obsessed, disciplined, and unapologetically cautious about where it places its bets. If the biology isn’t airtight, they won’t chase it — because real patients’ futures are on the line.

This mindset was shaped by leaders like Dr. Jeff Leiden, a cardiologist and molecular biologist who served as CEO from 2012 to 2020. Leiden took over when Vertex was still heavily reliant on a single cystic fibrosis franchise. He set out to transform the company into a sustainable biotech engine — not by expanding wildly, but by doubling down on what made Vertex special: deep genetic validation, careful execution, and therapies with game-changing impact, not just incremental benefits.

Today, under Reshma Kewalramani, Vertex’s first female CEO and one of the few women of color leading a major biotech company, that patient-first discipline has only intensified. A trained physician-scientist, Kewalramani brings the perspective of someone who’s sat across from families facing incurable diseases. Her leadership has kept Vertex’s bar for new programs high — but also boldly expanded the company’s reach into gene editing, regenerative medicine, and cell therapy, with the same determination that brought CF patients Kalydeco and Trikafta.

As of December 2024, Vertex’s people — more than 6,000 strong, many with PhDs, MDs, or both — are known for their collaborative, all-in approach. Lab scientists, clinical researchers, patient advocacy liaisons, and regulatory experts all pull in the same direction, fueled by stories of real patients whose lives have been changed forever. 

🧩 Segment 5: Lessons from Vertex – Resilience, Rigor, and Reinvention

So what can we learn from Vertex?

• Start with deep science: Every success story here is rooted in genetics and molecular biology.
• Patient partnerships matter: The Cystic Fibrosis Foundation’s support was pivotal.
• Focus, then diversify: Vertex didn’t jump into a dozen areas—they mastered one and then thoughtfully expanded.
• Execute brilliantly: They are one of the best clinical operators in biotech. Period.
• Stay private until you’re ready: Vertex waited to IPO until it had real science to show—unlike today’s hype-driven startups.

🏗️ Segment 6: What’s Next – The 2025 and Beyond Pipeline

As of mid-2025, Vertex has one of the most enviable late-stage pipelines in biotech. Highlights include:

• VX-548: A non-opioid pain drug targeting NaV1.8 channels. Phase 3 data looks promising for post-surgical and neuropathic pain.
• Casgevy (exa-cel): Now approved in the U.S. and Europe for sickle cell and beta thalassemia, with ongoing long-term follow-ups.
• VX-880/VX-264: Type 1 diabetes cell therapies in Phase 1/2 and 2 trials.
• VX-522: An mRNA-based therapy for CF patients with rare mutations who can’t benefit from Trikafta.
• Gene editing for DMD (Duchenne muscular dystrophy): In preclinical stage but a high-priority target.
• APOL1-mediated kidney disease: VX-147 is in advanced stages and could be first-in-class for this genetically defined kidney condition.

Vertex has also expanded its manufacturing footprint and expects its next-gen CF therapy, Vanza triple (a once-daily triple combination) to be the standard of care soon. It was just approved in the EU in July 2025.

More recently, in April 2024, Vertex and Alpine Immune Sciences, a biotech company focused on discovering and developing innovative, protein-based immunotherapies, today announced that the companies have entered into a definitive agreement under which Vertex will acquire Alpine for $65 per share or approximately $4.9 billion in cash. 

By the time this episode was recorded, Vertex’s stock sits at $470.33 a piece compared to about $4 when they IPO’ed, more than 10,000% increase in value. Market cap is at $120B. According to Glassdoor, an average salary for a PhD at Vertex varies depending on experience and specific role, but generally ranges from $184,000 to $318,000 per year. Vertex Pharmaceuticals has a headquarters in Boston and 23 office locations globally. The Vertex Companies, on the other hand, has locations in many other areas and has worked on projects in more than 40 countries, according to their website. 

🎵 Outro

That’s it for today’s Petri Dish Perspectives: Biotech Unleashed. From CF trailblazer to gene editing pioneer, Vertex Pharmaceuticals shows us that biotech success comes not just from innovation—but from persistence, patience, and principled execution.

🎧 If you liked this episode, please hit subscribe, leave a review, and share it with your biotech-curious friends. Got a company or therapeutic area you’d love to hear about? Drop me a message—I’d love to dig in.

Until next time, stay curious, stay evidence-based, and keep exploring the science shaping our future.

References

1. www.vrtx.com
2. www.wikipedia.org
3. www.finance.yahoo.com
4. www.endptnews.com
5. www.glassdoor.com  
6. www.investors.vrtx.com 

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