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Three plant-based pharmaceuticals: taxol, scopolamine and buprenorphine

Over the last 150 years, the pharmaceutical industry has focused on decoupling the production of medicinal compounds from their sources in the natural world, which are susceptible to unpredictable swings in supply due to natural events like wildfires, drought or floods. 

To accomplish this, the pharma industry has largely relied on synthetic chemistry, a discipline that has given scientists the ability to mimic natural compounds without relying on materials from the earth. This approach is now responsible for blockbuster drugs such as aspirin, L-DOPA and metformin (see our previous blog for more info). 

There remains a large number of naturally occurring compounds, however, that are either too complex or expensive to produce at scale through synthetic chemistry. As researchers continue to develop advanced manufacturing technologies, like synthetic biology-based fermentation, to produce these compounds at scale, the pharmaceutical industry still has to rely on naturally occurring plants as source materials for many drugs. 

Among the hundreds of plant-based pharmaceuticals globally, three of the most well known are the cancer medication taxol, the motion sickness drug scopolamine and the addiction treatment buprenorphine.

Taxol

Taxol, the most well-known natural-source cancer drug globally, is derived from the bark of the Pacific yew tree (Taxus brevifolia). Today, Taxol – which is the trade name for the molecule paclitaxel – is used in the treatment of breast, lung, and ovarian cancer, as well as Kaposi’s sarcoma.

First discovered in the 1960s, paclitaxel was extracted from samples of the Pacific yew’s bark by USDA researchers, and quickly found to have interesting cytotoxic activity that could limit runaway cell growth (as in cancerous tumors). While early trials of the molecule showed significant antitumor activity in mice, development toward the clinic was slow as scientists struggled to both harvest the naturally occurring molecule and to synthesize it in the lab.

Years later in the 1980s, larger clinical trials became possible when researchers discovered a method to extract a starting material of Taxol, 10-deacetyl-baccatin III, from the common yew Taxus baccata. By taking this structurally similar starting material and applying a few final chemical synthesis steps, scientists were able to create a semi-synthetic form of Taxol. Currently, a plant cell culture method is used to produce the drug at global scale, but because plants are multicellular organisms with cell walls these cultures are difficult and expensive to grow. Moving forward, scientists are exploring microbial engineering approaches to produce Taxol that are more efficient than current plant cell culture methods.

To date, Taxol is one of the commonly used cancer drugs ever manufactured, with annual sales of about $3 billion in 2019.

Scopolamine

Scopolamine and its biochemical precursor hyoscyamine are naturally occurring tropane alkaloids that are found in plants of the Solanaceae (nightshade) family such as mandrake, jimsonweed, and tomato. Scopolamine (also known as hyoscine) is classified as an anticholinergic agent, which means it blocks the action of acetylcholine, a type of neurotransmitter, and inhibits involuntary muscle movements and various bodily functions. Today, scopolamine is best known for its routine prescription as a treatment for nausea and vomiting related to motion sickness or surgery.

Plant extracts containing scopolamine have been used since ancient times as a medicinal treatment for gastrointestinal disorders. In 1880, the chemist Albert Ladenburg first isolated scopolamine from the nightshade plant Scopolia carniolica, and over the ensuing years, scientists discovered wider uses for the molecule. In the 1970s, the FDA approved a transdermal patch to deliver scopolamine to patients seeking treatment for motion sickness or postoperative nausea and vomiting.

Beyond a treatment for motion sickness, other tropane alkaloid drugs are being investigated to treat a variety of CNS disorders from Parkinson’s disease to other neuromuscular disorders. 

Buprenorphine

Buprenorphine is a semi-synthetic compound made from the starting materials thebaine or oripavine, which are naturally occurring alkaloids found in the opium poppy. Today, buprenorphine is used often as a treatment for opioid addiction and also as an analgesic – the antagonist properties of buprenorphine are equivalent to the popular treatment medication naltrexone, but as analgesic it is significantly more potent (and less addictive) than morphine.

Buprenorphine was first discovered in the 1960s as part of an attempt to find alternatives to morphine to treat narcotic addiction. Upon discovery, the molecule proved interesting because it is a partial agonist, which gives it a ceiling effect, meaning that the risk of overdose is attenuated. It was also difficult to produce at scale, as thebaine, the compound’s starting material, had to be sourced from specialized farms and was only available in limited quantities. (Even to this day, the dominant source of thebaine is farms in Australia, as the compound remains extremely difficult to produce through chemical synthesis.)

Initially used as an analgesic, studies of buprenorphine as a treatment for opioid use disorder in the late 1990s and early 2000s – which was associated with growing numbers of overdoses – were becoming increasingly popular. After compelling evidence, the FDA approved buprenorphine as a treatment for opioid addiction in 2002.

Buprenorphine has steadily gained mainstream acceptance, and the drug achieved over $3 billion in 2019 sales.

From Ingredients to Inspiration

Plants produce a dizzying array of medicinal compounds. Today, the pharmaceutical industry spends billions of dollars every year mimicking these compounds through synthetic chemistry, or isolating these compounds from the plants themselves to produce drugs like taxol, scopolamine and buprenorphine. In the coming years, as scientists scale up alternative manufacturing technologies like synthetic biology-based fermentation, pharma will continue to shift from relying on plants as raw materials to viewing plants as inspiration for medicines.

*Drug sales are provided by Cortellis Generics Intelligence™ (formerly Newport), ©Clarivate

Appropriate regulatory submissions will be prepared and submitted to support Antheia’s customers who need to reference and access necessary process-related information.

Yihui Zhu, PhD

Head of Fermentation

Yihui leads the fermentation team at Antheia. With over 25 years of hands-on experience in the field, he brings in-depth knowledge and expertise in microbial metabolism and fermentation process development. He is also skilled in developing comprehensive fermentation data collection, analysis, and visualization systems. Prior to joining Antheia, he served as a fermentation lead at Intrexon and Codexis where he successfully built fermentation labs and teams and led multiple biofuel and biochemical projects to reach stretch milestones and tech transfer. Yihui is passionate about the potential of fermentation and is dedicated to advancing the field through innovative research and development.

Yen-Hsiang Wang, PhD

Head of Strategy, Partnerships, and Finance

Yen-Hsiang leads strategy, partnerships and finance at Antheia. He completed his M.S. and Ph.D. in Bioengineering at Stanford, with extensive research experience in synthetic biology, metabolic engineering and computational modeling. Before joining Antheia, he worked at McKinsey and Tencent with a strong focus in corporate strategy and big data/advanced analytics. At Tencent, he served as Director of Strategy and Business Development for the AI Lab, leading corporate initiatives in healthcare AI/ML applications and commercialization. He also served in AI4H (Artificial Intelligence for Health), a collaboration between WHO and ITU, to establish global standards for AI in healthcare.

Audrey Wang

Head of Financial Planning and Analysis

Audrey leads financial planning and analysis at Antheia. With an MBA from Washington University in St. Louis, Audrey is passionate about leveraging financial analysis, digital technology, and data analytics to guide companies in making optimal investments and strategic business decisions. Audrey has a decade of experience in helping companies solve unique problems and creating long-term impact with unconventional approaches. Before joining Antheia, she was at Vir Biotechnology and Merck where she led various FP&A workstreams, including investment valuation, asset prioritization, and manufacturing sites operation finance support. Audrey completed CFA Level II and passed the U.S. CPA exam in 2011.

Antonij Tjahjadi, CPA

Head of Accounting

Antonij Tjahjadi leads accounting at Antheia and holds active CPA license. He joined Antheia with more than 20 years of experience in corporate accounting, bringing deep expertise in ramping up accounting operations for start-up companies, SEC reporting/technical accounting, and SOX implementation efforts. Before joining Antheia, he held various leading roles in both public and private company settings, including directing accounting functions at Ambys Medicines, where he successfully implemented Netsuite with Point Purchasing integration and set up various accounting policies and processes, and played a key role in the initial public offering of Nutanix, Inc.

Ken Takeoka

Head of Biology

Ken leads the Biology team at Antheia, which incorporates both strain and protein engineering functions. He has more than 16 years of experience in the synthetic biology field, working with leading companies, including Amyris and Novartis. One of his passions is molecular biology tool development and he previously worked to build the foundation for the automated strain engineering pipeline at Amyris. At Novartis, he modernized the molecular biology techniques and established a platform to model mechanisms of antibiotic resistance in a range of organisms.

Suzanne Sato

Head of Downstream Processing

Suzy leads downstream chemistry processes at Antheia. She has 19 years of experience in process development, including route development through synthetic chemistry and scale-up of small molecule APIs for GPCR targets under cGMP for Phase I-III trials. Before joining Antheia, Suzy led a full DSP team at Amyris where she successfully pivoted developments from biofuels hydrocarbon products to pharmaceutical intermediate, flavor, fragrance and nutraceutical products. She led a team that scaled 11 products and took five products to commercial manufacturing.

Farrah Pulce, PMP

Head of Project Management

Farrah leads program and project management at Antheia. She has over 20 years of experience leading program and project management, operations, and engineering for companies across the CPG, aerospace, and automotive industries. Prior to joining Antheia, Farrah implemented and led the sustaining program management team at Impossible Foods. She also led product operations, project management, and cost optimization at Blue Bottle Coffee and Tyson Foods to develop and commercialize new products. As a certified project management professional (PMP), Farrah has a proven record of successful project delivery, improving project management practices, and building collaborative teams.

Jordyn Lee

Head of Communications

Jordyn leads communications and external affairs at Antheia. She brings a decade of multidisciplinary communications experience in helping companies make complex science and technology accessible to broad audiences, all while maintaining technical accuracy and integrity. She has a passion for visionary storytelling and translating impact across the entire communications ecosystem – her work has spanned from public relations to corporate communications to marketing. Jordyn has served as an advisor to a number of different life sciences companies and most recently led corporate communications at Amyris.

Ben Kotopka, PhD

Head of Data Science

As Head of Data Science at Antheia, Ben manages in-house software development and external partnerships for storing and interpreting research data, executing bioinformatics analyses, and streamlining business processes. Prior to Antheia, Ben worked as an academic researcher at the intersection of machine learning, bioinformatics, and synthetic biology. Following this, as an entrepreneur and consultant, he developed and deployed data science solutions for biotechnology applications ranging from metabolomics-driven compound discovery to MRI segmentation.

Guerin Kob

Head of Supply Chain

Guerin is responsible for leading the design, development, management and improvement of Antheia’s end-to-end global supply chain. He has over 15 years of experience leading high-performing supply chain and procurement teams at leading biotechnology and specialty chemical companies, with extensive experience in process development and end-to-end supply chain optimization. Prior to joining Antheia, Guerin served as Senior Director of Global Supply Chain for Sumitomo Chemical’s biotechnology division with Valent Biosciences, where he led the end-to end supply chain including procurement, logistics and distribution, integrated business planning, materials management, customer service, and supply planning functions globally.

Pavel Aronov, PhD

Head of Bioanalytics

Pavel leads the Bioanalytics team at Antheia. He has 20 years of experience in analytical and clinical chemistry, mass spectrometry, chromatography, and metabolomics. Pavel built and led the original Chemistry and Analytics team at Impossible Foods enabling strain development, fermentation, DSP, regulatory, QC, and scale-up of leghemoglobin biomanufacturing. During his academic career at UC Davis and Stanford University Pavel developed a vitamin D assay used by all major clinical diagnostics laboratories and pioneered metabolomics studies to investigate kidney disease and microbiome.

Jesse Ahrendt

Head of Quality Assurance and Regulatory Affairs

Jesse has more than 25 years of experience in regulatory affairs, quality systems, manufacturing quality, and regulated industries, ranging from early- to late-stage pharmaceuticals, biomanufacturing, consumer care, and medical devices. He has supported global product launches and the underlying quality supply chain components in industries that require strict adherence to internationally accepted quality standards. Before Antheia, he led quality efforts at Zymergen and Sandoz, and supported many global pharmaceutical companies during his time in Biotech Consulting at NSF International, all to bring quality to the forefront in manufacturing, standardize global processes, and support customer regulatory requirements.

Heidi Pucel

Chief People Officer

Heidi is a results-driven human resources executive and HR business partner who leverages decades of experience in empowering, motivating, and inspiring to drive transformation within high-performing and rapidly-growing workforces. A certified executive coach and passionate advocate for people-oriented solutions, Pucel serves as a partner to executive teams to design programs that support employee development, engagement, and recruitment and retention. Pucel most recently served as Chief People Officer for Countsy, where she worked as an interim HR executive for clients in the biotechnology and software industries, such as Ceribell and Tune Therapeutics.

Zack McGahey

Chief Operating Officer

Zack is a leading executive in operations management, specializing in bioprocess engineering and manufacturing management. He has over 20 years of experience leading manufacturing functions for companies across the pharmaceutical, synthetic biology, diagnostics, and automotive industries. Before joining Antheia, Zack was VP of manufacturing and capex project management at Zymergen. He also gained experience managing commercial scale facilities operations for Tesla, where he was responsible for managing 10 million square feet of factory, lab and warehouse space during the Model 3 ramp.

Kristy Hawkins, PhD

Co-Founder & CSO

Kristy has over 20 years of experience in the field of synthetic biology, focusing on yeast metabolic engineering for the production of small molecules. She did the founding work on the benzylisoquinoline alkaloid pathway during her graduate studies and gained valuable industry experience at Amyris and Lygos. Kristy is an expert in tool development, high-throughput screening, and host strain and heterologous pathway engineering.

Christina Smolke, PhD

Co-Founder & CEO

Christina is a pioneer in synthetic biology and metabolic engineering, where she has over 20 years of experience. As Professor of Bioengineering and Chemical Engineering at Stanford University, her laboratory led the breakthrough research to engineer baker’s yeast to produce some of the most complex and valuable medicines known. Under her leadership, Antheia’s synthetic biology platform enables new possibilities for drug discovery and efficient, sustainable, transparent, and on-demand drug manufacturing at scale. Her vision and accomplishments have garnered numerous awards, including the Chan-Zuckerberg Biohub Investigator, NIH Director’s Pioneer Award, Nature’s 10, Novozymes Award for Excellence in Biochemical Engineering, and TR35 Award.

Antheia Completes Successful Product Validation

Appropriate regulatory submissions will be prepared and submitted to support Antheia’s customers who need to reference and access necessary process-related information.