Carlos A. Martinez used nature’s catalysts to make Paxlovid a reality

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Carlos A. Martinez sits on a piano bench in front of a red curtain.

Credit: Luis Manuel Diaz

Carlos A. Martinez

In 2020, Carlos A. Martinez and his team at Pfizer were racing to massively scale up production of nirmatrelvir, a key component of the COVID-19 antiviral Paxlovid. While it can take years for a drug candidate to make it to patients, Pfizer brought nirmatrelvir to market in only 17 months (ACS Cent. Sci. 2023, DOI: 10.1021/acscentsci.3c00145).

Vitals

Hometown: Cali, Colombia

Education: BS, chemistry, University of Valle, 1994; PhD, chemistry, University of Florida, 2000

Current position: Director of the Biocatalysis Center of Excellence, Pfizer

Hobbies: Running, playing the piano, and gardening

Favorite song: “Somewhere over the Rainbow” by Israel “IZ” Kamakawiwo’ole. And I enjoy classical piano music, can listen to Chopin and Beethoven for hours.

Recent project: Built a pond at my house

I am: Latino

Martinez, director of Pfizer’s Biocatalysis Center of Excellence, played a key role in making the starting material for a main fragment of nirmatrelvir using enzymes. “As a company, we all felt that the development of the vaccine and antiviral were the most important things at the time,” Martinez says.

He says the biggest challenge was not the scientific aspects of the process but the need to work quickly across internal and external bureaucracy. The team had to work seamlessly to meet grueling timelines, monitor technology transfers to commercial suppliers, and ensure uniformity across manufacturers and vendors.

As part of the larger efforts at Pfizer to bring Paxlovid to market, his team repurposed and adapted an enzymatic route to make an intermediate previously used in the synthesis of boceprevir, a hepatitis C treatment that was withdrawn from the market in 2015 (J. Am. Chem. Soc. 2012, DOI: 10.1021/ja3010495). This fragment had been made previously, but his team couldn’t find enough documents detailing the drug’s production. “We almost had to reinvent the process,” Martinez says. Drawing on public domain knowledge and using an enzyme produced by Codexis, he and his group were able to double the productivity compared with that of the previous process route.

Martinez is used to solving tough problems. He’s led the biocatalysis efforts at Pfizer for more than 20 years. He was awarded the 2024 American Chemical Society Award in Industrial Chemistry for his “outstanding contributions to chemical research in the industrial context.”

Martinez’s journey, defined by creatively using enzymatic reactions on the metric ton scale to produce lifesaving drugs, began in a library in his hometown of Cali, Colombia, in the 1980s. He loved reading about the chemical elements. “I always thought there was something wonderful about the periodic table,” Martinez says. A biochemistry class during his fourth year of undergraduate studies at the University of Valle solidified his desire to do chemistry research that could make an impact on human health.

After completing his undergraduate studies, Martinez served as a summer visiting student in the lab of Jon Stewart at the University of Florida. “That’s how I met the field of biocatalysis for the first time,” Martinez says. “I worked really hard as a summer intern and eventually received an invitation to join Stewart’s group. It ended up being a very good move for me.”

Stewart says Martinez joined his lab as it was just starting up, and Martinez’s time there was part of “the foundation of everything that came after” in the lab. Martinez then served as a postdoctoral fellow in Frances Arnold’s lab at the California Institute of Technology, where he was a key contributor in the lab’s early efforts at generating new enzymes by recombining similar sequences from different organisms. “I came away with an understanding that the development of a process could involve the development of the catalyst,” Martinez says, instead of just trying to make a commercially available enzyme fit a synthetic target.

There’s a lot to be discovered and a lot of value to be brought to the chemical research ecosystem in the US and beyond from students from Latin America.

Martinez started his professional career in the first biocatalysis group at Pfizer in 2001, excited about the potential to apply the technique in industrial processes. He knew scaling up would be key. “Unless we were able to impact projects at large scale, biocatalysis was never going to be integrated into the workflows of how we do business,” he says.

The group’s first success story came when it successfully developed an enzymatic manufacturing process for pregabalin, the active ingredient in the nerve-pain medication Lyrica. The group’s technique used a commercially available lipase enzyme (Org. Process Res. Dev. 2008, DOI: 10.1021/op7002248).

“It was the first time we were able to identify an enzyme and a process that could be scaled up,” says Daniel Yazbeck, a founding member of the Pfizer biocatalysis group who now serves as CEO of the private investment fund Yazbeck & Co. The new process improved yields and efficiency and reduced waste streams compared with the first-generation route.

Carlos A. Martinez stands in front of a pond.

Credit: Luis Manuel Diaz

“This set the stage for future success stories,” Martinez says. “It sent a message that this biocatalysis technology was scalable,” giving the team much-needed credibility.

Yazbeck says the first few years of starting up Pfizer’s biocatalysis group were exciting and intense. “Biocatalysis was a relatively new field, and we were spearheading Pfizer’s efforts,” he says. Through it all, Martinez was methodical, steady, and consistent. “Carlos was always driven to do the science and make it work,” Yazbeck says. “Consistent and steady wins the game.”

When he’s not diligently racking up accolades or helping bring lifesaving medications to reality, Martinez tries to encourage students from his home country to recognize their own talent. “I’m very proud of my upbringing in Colombia,” he says. “The education I received was top tier and quite rigorous.”

Martinez gives talks at Colombian universities and maintains an informal network of Colombian scientists. He hopes his encouragement will build confidence in students to pursue graduate studies in places like the US. “There’s a lot to be discovered and a lot of value to be brought to the chemical research ecosystem in the US and beyond from students from Latin America.”

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