Lalo Flores, CEO at Century Therapeutics, on Developing Next-Generation Cell Therapies

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Lalo Flores, CEO at Century Therapeutics

In this episode, we sat down with Dr. Osvaldo (Lalo) Flores, CEO at Century Therapeutics, a biotechnology company developing transformative allogeneic cell therapies to create products for both hematological and solid tumor malignancies. In January 2022, Century entered into a strategic collaboration with Bristol Myers Squibb (BMS) to develop induced pluripotent stem cell (IPSC)-derived allogeneic cell therapies. Century is based in Philadelphia, PA.

In this conversation, Lalo and I discussed:

• The varied experiences of working in small biotech start-ups versus big pharma companies
• Identifying a large unmet need in hepatitis B and building a first-in-class company, Novira Therapeutics, to address it
• The cell therapy revolution and how Century Therapeutics is innovating beyond “Generation 1.0”
• How small biotech start-ups and big pharma companies can synergistically collaborate to advance programs efficiently
• Philadelphia’s status as a biotech hub with diverse talent from both academia and industry

Start to 3:50: Science Requires Curiosity, Discipline, and Passion

• On getting exposed early to science: Born in the Northern Patagonia region of Chile, Lalo was raised by two scientists — his father, a veterinarian and his mother, an agricultural engineer. At 17, Lalo was motivated to build his career as a scientist and arrived in the U.S. to pursue his PhD in Biochemistry and Molecular Biology at Rutgers University.
• On learning the intangibles: During his graduate training, Lalo joined forces with an Associate Professor who was just starting his lab. Lalo cites these early days as the training ground where he learned the importance of the hard work, discipline, and passion required to succeed in science, especially in the face of numerous setbacks.

3:50 to 7:45: R&D Through the Lens of Big Pharma and Biotech Start-Ups

• On transitioning to industry via a start-up: Lalo was a talented graduate student, having published many scientific papers and joined Ron Evans lab at Salk Institute as a Postdoc. However, he was quickly recruited to join Tularik, an emerging biotech start-up, where he caught the entrepreneurship “bug.”

“When you join an early-stage start-up company, it’s really exciting. I could sense the energy of all the scientists … being offered the opportunity to do science that could … one day help patients.”

• On recognizing the power of big pharma: While at Tularik, Lalo ran the company’s partnership with Merck and ended up joining Merck after Tularik was acquired in 2004. Lalo worked his way to becoming Department Head of Molecular Endocrinology during which time he ran a number of discovery and development programs. While at Merck, Lalo came to recognize the power of a big pharma company, which holds significant institutional knowledge, experience, and resources.

7:45 to 16:10: Identifying an Unmet Need and Addressing It at Novira Therapeutics

• On understanding what’s next: Lalo left Merck after nine years and started Novira Therapeutics to address hepatitis B. At the time, the industry focused mainly on hepatitis C but that problem was nearly solved; Lalo saw hepatitis B, a chronic viral infection with no cure, as next in line.
• On pursuing an “undruggable” target: Lalo and his partner identified papers that validated a new target, the capsid of the virus, which was considered undruggable at the time. Together, they formed Novira and raised $500K in Seed financing. Today, multiple capsid inhibitors are in development with Novira being the pioneer in the field.

“[ Capsids ] are structural proteins that don’t bind to traditional binding sites, so they’ve been ignored by the industry. I said ‘Listen, this is something I can do.’”

• On running an efficient organization: In the early days, the Novira team consisted of just Lalo and his partner, George Hartman. The two of them did most of the thinking while outsourcing the legwork to external contract research organizations (CROs) like WuXi AppTec and Evotec. Once they gained traction, they raised a Series A financing led by 5AM Ventures, a top-tier venture capital firm, in 2012. With just the Series A funds, Lalo and team were able to move quickly and execute on their plan which ultimately led to Novira’s acquisition by Johnson & Johnson.

16:10 to 31:50: Building Century Therapeutics, a Next-Generation Cell Therapy Company in Philadelphia

• On drawing inspiration from CAR-T pioneers: Lalo reminds us of the pioneering work done by U Penn and biotech companies like Juno Therapeutics and Kite Pharma in developing novel CAR-T therapies for patients with hematological malignancies. The early data were remarkable with several patients being cured of their cancers after multiple lines of traditional therapies. This promise inspired an entire industry to pursue cell therapy further, even beyond hematological malignancies.

“This pioneering work is what inspired so many, including myself. Having worked my entire career in R&D, this concept of using living cells as drugs … I recognized was the beginning of a new era.”

• On innovating beyond “Generation 1.0:” The first generation (i.e., Generation 1.0) of cell therapies were incredibly impactful but bore several limitations, such as the requirement of harvesting the patients’ own cells and inability to sufficiently engineer the cells to achieve the desired durability and potency. Century’s platform uses IPSC-derived cells instead of patient- or donor-derived cells, which allows Century to limitlessly genetically modify cells using modern precision gene editing tools and use single cell clones to create master cell lines that can be used in manufacturing to ensure homogenous products.
• On establishing synergistic partnerships: While headlines typically highlight the financial impact of multi-billion-dollar partnerships like Century’s with BMS, Lalo was sure to emphasize the strategic value as well. Century’s partnership with BMS allows the company to pursue further cancer indications (of which there’re many) with an industry-leading partner that contributes complementary technologies and scientific expertise along with significant financial investment.

“This is a perfect example of the power of partnerships and how they can add so much value to both the biotech company and big pharma partner.”

• On building Century in Philadelphia: Lalo describes Philadelphia’s ecosystem as “special” in that it combines academic talent from the likes of U Penn, Drexel, and Temple with industry talent from the many big pharma companies in the region. Above all, it’s a beautiful city to live and work in!

31:50 to End: Advice to the Next Generation of Business Leaders

• On being open minded: Lalo encourages emerging leaders to keep an open mind and focus on learning. Optimize for learning and personal growth, especially under the guidance of mentors who care. Most importantly, there’s no one path to success.