EXECUTIVE INTERVIEW - Botanical Solution Inc.: Launching a Revolution in Economical & Environmentally Sustainable QS-21 Vaccine Adjuvant Production

Gastón Salinas is a visionary leader in the field of sustainable biotechnology, renowned for his transformative contributions to pharmaceutical and agricultural innovations. As the Chief Executive Officer of Botanical Solution Inc. (BSI), a company he co-founded in 2013 and has led as CEO of the US-based entity since 2019, Mr. Salinas has played a pivotal role in the company’s emergence as a global leader in Advanced Botanical Materials (ABM). Under his strategic direction, BSI has pioneered groundbreaking plant-based biofungicides, such as Quillibrium®, and sustainable manufacturing of the critical vaccine adjuvant QS-21, traditionally obtained from tree bark, which is used in immunizations for shingles, malaria, RSV, and COVID-19.

Chile, is where Mr. Salinas and BSI cofounder Gustavo Zúñiga, PhD, called home. Chile is also where a beautiful, adjuvant-producing tree grows, called the Quillaja saponaria. Dr. Zúñiga proved that the Quillaja Saponaria could be grown through plant tissue culture and achieve a scalable manufacturing system. The pair recognized they could produce their own plants, and the first application was to use the plant extract as a biofungicide. They soon discovered its usage for vaccine adjuvants – the gold standard vaccine adjuvant of which there is a shortage. Mr. Salinas and Dr. Zúñiga set out to address this shortage by cultivating a virtually unlimited supply to meet the world’s needs.

While Chile was a good pilot market for the technology, Mr. Salinas wanted to bring the value proposition to a global scale. He moved to Davis, California in 2019, right before the COVID pandemic. He quickly learned that there was a huge interest in the QS-21 molecule, which he says turned out to be quite the “box of surprises.”

Fast forward to 2024 when BSI secured $23.3 million in Series A funding, facilitating key partnerships, including a significant collaboration with Croda Pharma, and driving BSI’s expansion into new markets. Last year, BSI won two Pharmaceutical Technology Excellence Awards: the Innovation award for its innovative manufacturing process that sustainably produces QS-21, reducing costs and environmental impact; the Business Expansion award for strategic scaling of production capabilities, R&D advancements, and successful market partnerships, which have positioned BSI as a leader in the rapidly growing botanical ingredients market and a key player in global vaccine development.

Mr. Salinas recently spoke with Drug Development & Delivery about the company’s transition from agriculture to pharmaceuticals, addressing the global shortage of QS-21, and developing the QS-21 gold standard vaccine.

Q: Describe BSI’s transition from serving the agriculture market to the pharmaceutical sector?

A: We had the opportunity to look at a much larger business opportunity for the compound. We were selling the agriculture product to farmers through our exclusive distributor Syngenta for about $30 to $50 per liter whereas a single gram of the pure QS-21 compound in pharmaceutical grade was worth up to $400,000. This is night and day economic impact. We proved on the agriculture side that we were able to successfully de-risk the technology for growing the plant at commercial scale and rolling out the technology to as many countries as possible. This gave us a solid foundation to translate the agriculture value proposition and repurpose to the pharmaceutical space.

Q: Can you please explain how QS-21 was traditionally obtained and how BSI has revolutionized the process?

A: These are very old Quillaja saponaria trees that mostly grow in Chile. The plant naturally expresses the QS-21 compound as a response to an environmental condition, such as a pest attack or stress. No other trees produce the compound. Traditionally, you needed to chop down the tree to get the compound from the inner bark. It’s a real challenge. The older the tree, the higher likelihood of having higher yield of QS-21 to make it economically feasible.

In contrast, BSI grows QS biomass year round indoors using a proprietary plant tissue culture platform. The process is a combination of proprietary handling and environmental protocols, know-how, and plant lines that, when combined, allow growth of green QS tissue (biomass) while eliciting production and accumulation of QS-21, among other compounds. We have learned how to stress the plant tissue to accumulate the compound in sufficient quantities to make it economically feasible. We harvest the biomass on a weekly basis to extract and get down to the pure compound. Traditionally, the industry has relied on reverse-phase HPLC methods for QS-21 purification, which is highly demanding on the use of organic solvents like acetonitrile, creating another even greater sustainability issue. BSI has already solved this problem, too.

Q: What is meant by “gold standard” solutions and what is the QS-21 gold standard vaccine?

A: Vaccines elicit so-called Th1 and/or Th2 responses. Th2 responses are mediated by antibodies whereas Th1 responses are mediated by cells, particularly antigen-specific killer cells.

Alum only induces Th2 responses while QS-21 induces both Th1 and Th2 responses. Alum was commercially introduced in the 1930s and has worked in many vaccines (S. pneumonia, HPV, and polio). Thus, if the invading organism can be eliminated, then the vaccine usually can use Alum as an adjuvant. But, if the offending organism establishes a persistent commensal infection, the vaccine needs to elicit a Th2 response. AS01b with QS-21 was commercially introduced in 2017 and gives both a Th1 (cell mediated immunity) and a Th2 (antibody response). This is important and has enabled new vaccines such as the Shingrix® (herpes zoster), Mosquirix® (malaria), and Arexvy® (RSV) vaccines from GSK. All three of these GSK vaccines are caused by infectious agents that develop persistent commensal infections that our immune systems cannot fully clear.

Q: Why is the QS-21 supply chain so fragile?

A: Some have tried to fully synthesize QS-21 in the past, but no prior effort has succeeded in making it cost effectively, likely because there are too many steps involved. Hence, the industry has continued to need very old QS trees as the unique source of raw materials for obtaining QS saponins. There are deforestation laws in Chile intended to prevent the over exploitation of these ancestral trees. QS saponins are used in multiple industries that include food and beverages, cosmetics, industrial, agricultural, and pharmaceutical applications. As demand for these products continues to grow, more pressure will be put on the supply chain, increasing the sustainability burden. In addition to the importance of producing and manufacturing of QS-21 is the need for a robust supply chain to make sure there will be enough for current and future highly efficacious vaccines that may require this distinct component. If we were to face another global pandemic, the need for securing or stockpiling these materials is one of those lessons learned from the last pandemic. The technology would allow the US and other countries to have a local source of this distinct compound, if needed.

Q: What is so distinctive about QS-21?

A: The compound is not new. It’s been in the literature for more than 30 years. It wasn’t until 2017 that it made it into a commercial product, in this case Shingrix. What’s so distinctive about this molecule is its ability to trigger specific immune responses (Th1 and Th2) and let the immune system recognize the antigens to deliver the expected result. It has been proven, at least for shingles, that when you combine QS-21 with an antigen, you can get almost lifetime durability. After COVID, durability of immunity to vaccination or protection has become a hot topic. For many, receiving a booster shot every six months is a no-go. The holy grail would be to have a lifelong protection against diseases with fewer vaccine doses. Efficacy and durability are associated with QS-21.

Q: Beyond Shingrix, how close is industry to producing other longer-lasting vaccines with QS-21 and for what indications?

A: There is one FDA-approved vaccine against COVID-19, which is adjuvanted with QS-21 and other Quillaja Saponaria saponins. This adjuvant system is called Matrix M. The vaccine was originally developed and marketed by Novavax and soon will be distributed by Sanofi. There are also COVID and flu vaccine candidates adjuvanted with Matrix undergoing clinical testing. My dream is to make QS-21 available for malaria, tuberculosis, respiratory syncytial virus, and other vaccines. That dream will come true not too far from now for high-impact countries and those less privileged.

Q: Please describe the partnership between BSI and Croda.

A: In the last five years, Croda has done a fantastic job trying to secure access to key pharmaceutical ingredients for commercial and clinically relevant vaccines. QS-21 and QS supplements fall into that category. BSI will supply QS-21 to Croda, and Croda will supply QS-21 to pharma companies as an excipient or in formulations. Croda has developed internally and in-licensed the most clinically relevant vaccine adjuvant systems portfolio that need QS-21 to work. We believe Croda is a company best positioned to help us grow the QS-21 market not only for FDA-approved vaccines, but also for future new vaccines.

Q: What is BSI doing with the $23.3 million in Series A funding and how are you attracting other investors?

A: This year, we plan to roll out QS-21 under GMP standards in connection with the Croda partnership. We have a thorough business plan to keep investing in key manufacturing capabilities required to make QS-21 at greater scale. There is also growing interest in other compounds that come from the QS plant, such as QS-7. That is the next low hanging fruit. Both QS-21 and QS-7 compounds are present in FDA-approved vaccines. QS-7 has been studied to be less reactogenic than QS-21 in a preclinical setting, which may translate into less pain and side effects. Both compounds follow similar purification systems.

There are at least three or four other molecules that have kept pharma companies interested in us and we are in the best position to make them available. So, we could be moving from supplying one molecule to up to four. As a company, we have learned we need to create and invest in capabilities internally to make the compounds and formulate in different presentations. In connection with the expansion plan, we will pursue series B funding later this year.