Launched in June 2018, the BioProcess Insider digital information portal delivers the latest financial and business news and expert insider views influencing the commercialization of biopharmaceuticals. Here are just a few recent stories edited for our space limitations in print. For more discussion and in-depth analysis, check out the website at www.bioprocessinsider.com. Every edition provides expert and insider perspectives on current financial movements and deal-making; the newest technology purchases and capacity investments; regulations affecting the bioprocessing sector; global market actions and reactions; and industry trends.

Janssen Opens HIV Vaccine Plant

Janssen Pharmaceuticals, a subsidiary of Johnson & Johnson, has opened a new single-use biomanufacturing facility to support commercialization of a preventative human immunodeficiency virus (HIV) vaccine candidate in development. Representing an investment of €72 million ($82 million), the multipurpose vaccine-production facility was inaugurated on 25 October 2018 in Leiden, the Netherlands. It will be used initially to manufacture an investigational mosaic HIV-1 preventive vaccine.

The plant was commissioned following the 2014 Ebola outbreak in West Africa, said Dirk Redlich (vice president of strategy and operations leader at Janssen Vaccines) in a recent press tour. At the time, Janssen’s facility in Switzerland made small volumes of an investigational preventive Ebola prime-boost vaccine regimen: two million doses at 10-L scale. But the company’s leadership wanted a large-scale facility to prepare for commercialization of more vaccines, Redlich said, so they decided to construct this new plant. It is equipped with single-use bioreactors to a scale of 1,000 L. Using Janssen’s proprietary human PER.C6 cell line to make adenoviral vectors, Redlich said, “we can produce between 100 and 300 million doses of vaccine with a rather small 1,000-L volume,” depending on the disease.

Chasing the Holy Grail: The first product to be made at this site will not be an Ebola vaccine, but rather a preventative HIV vaccine. Janssen has been involved in such product development since acquiring TiboTec Therapeutics in 2011. Tibotec was the first company to enter the market with an effective drug, which (along with other drugs) changed HIV infection from a death sentence to a treatable disease. Even so, it is still a major health concern: 40 million people live with HIV or acquired immune deficiency syndrome (AIDS) around the world, 22 million of whom have no access to therapies.

Thus a preventative vaccine against the infection would be “the holy grail,” said Hanneke Schuitemaker (vice president of viral-vaccine discovery and translational medicine at Janssen). She pointed to her company’s current HIV vaccine program, which is currently in the phase 2b clinical development stage.

According to Janssen, that product candidate is stable at temperatures up to 28° C. The platform elicits both antibody responses and cellular responses, and the vaccine virus is engineered to be incapable of replication. “The PER.C6 cell line has a sequence that allows the virus to grow through a highly efficient platform,” explained Redlich, “so you can grow viruses in numbers not seen before. Normal cell lines have about a million cells per milliliter, but we can have up to 100 million cells/mL.” Primary analysis of the phase 2b proof-of-concept study is planned for 2021.

“Biopharma” Draws Investment Dollars

With consistent yearly growth of ~12%, the biopharmaceutical sector is the “favored child” of the drug industry, according to Eric Langer (president and managing partner of BioPlan Associates). At the first BIOLive event this past October at CPhI Worldwide in Madrid, Spain, he told delegates that innovation and sales revenue have driven a divide between the large-molecule and traditional small-molecule pharmaceutical segments.

“Today’s market is around $250 billion in biopharma sales,” he said. “This is still an emerging market, but what we are seeing here is that 25% of all pharmaceutical revenue is now ‘bio’ — large molecules. This represents a growth of 57 times since the emergence of biopharma [28 years ago], but more importantly a 12% annual growth rate over the past 12 years.”

That has given the overall pharmaceutical industry a level of consistency that it never had before, he argued. “Pharma has seen around a 4% growth rate, but biopharma has been demonstrating this 12% growth rate year-on-year, and that’s very exciting for investors.” Furthermore, 45% of products in the drug pipeline are biologics, which this makes biopharmaceutical companies even more attractive to investors looking for big payoffs.

Investors’ Favored Child: The label of biopharmaceutical is being misused by traditional small-molecule drug makers, Langer cautioned. When a company calls itself a “biopharma,” that implies an element of biotechnology. “It sounds higher tech,” he said, but just because you use a biotechnologic component in your development process, that does not mean your product is a true biopharmaceutical. However, it does make your company potentially more “investable” by people who want to be part of this “new wave” of drug making. Langer added that the terms biotech and biopharma are “sexier than the word drug,” which is driving investment in small innovative biotechnology organizations and in traditional “big pharma” companies that have embraced the bio- prefix.

Langer also talked about why the large pharmaceutical companies are reluctant to integrate fully their actual biotechnology subsidiaries and acquisitions into their overarching businesses. For example, Janssen Biotech is distinguished from its parent company Johnson & Johnson; Genentech is the biotechnology part of the Roche group. “In a way, the biopharma community is getting special treatment from their parent companies,” he said. “They are not so integrated as one might have expected, and they continue to have a certain degree of independence.”

That’s partly because big pharma sees its biopharmaceutical groups as favored children simply because they are more profitable than the classical drug business. But companies also are aware that innovation is driven from the biotechnology side of the industry, so they are reluctant to merge that too much into their traditional organizations: “If you integrate too hard, you run the risk of killing that innovation,” Langer said.

Merck Expanding in Ireland

Merck & Co. touts its newly announced construction of a vaccine and biologics production site in County Carlow as its latest commitment to Ireland. Known as MSD outside North America, the company will construct its second plant there, about 80 km southwest of Dublin, and create 170 new jobs. The facility will focus on production of vaccines and biologics, with an expansion of warehouse and laboratory services. Spokesperson Barbara Coyle told BioProcess Insider, “Recruitment for the new facility will commence immediately, and it is intended that new manufacturing operations will commence in 2023.”

No specific financial details have been disclosed, but this follows a number of recent investments in MSD’s Irish manufacturing network: In 2017, the company announced investment of €280 million ($320 million) to expand its Brinny site (County Cork) and build the first standalone vaccine and biologics facility outside the United States in Carlow. And in February 2018, the company announced plans to build a plant at its former women’s healthcare product business in Dublin to manufacture the top-selling cancer drug Keytruda (pembrolizumab), which will create 350 jobs.

“The decision to further invest in Carlow is a real testament to the talent of the current Carlow team and MSD Ireland’s wider employee base,” Coyle said, “and reinforces MSD’s commitment to Ireland, further strengthening our 50-year strong legacy here. Construction of this additional facility adds to our ability to offer current and future employees an opportunity to experience all elements of pharmaceutical and biotech manufacturing within Ireland.”

Heather Humphreys (Ireland’s Minister for Business, Enterprise, and Innovation) described the new facility as “a tremendous asset” to the country’s drug industry that “will deepen the great partnership between Ireland and the company.” Coyle said that MSD’s continued Irish investment reflects “continued access to highly skilled employees as well as collaborative partnerships with the government and third-level institutions.”

For decades, Ireland has been a major drug-manufacturing hub, spurred by low corporate tax rates and a highly skilled workforce. The language, proximity to Europe, and EU membership also have boosted multinational investment. The biopharmaceutical sector has been encouraged further by government support, including the funding and establishment of the National Institute for Bioprocessing Research and Training (NIBRT). Described as a “flight simulator for biomanufacturing” NIBRT has trained more than 4,000 people each year in bioprocessing since it opened at a site in Dublin in 2011. The country has seen multimillion-euro investments from other companies, including Eli Lilly, Pfizer, Takeda, and WuXi Biologics.

4D Bioprinting Instead of Animal Testing?

Drug maker Servier Laboratories has announced a deal with supplier Poietis (both in France) to use its “four-dimensional” (4D) bioprinting technology for development and production of liver tissues to use in preclinical testing. Bruno Brisson (Poietis cofounder and vice president of business development) told BioProcess Insider that his company’s technology works through “layer-by-layer additive biofabrication of functional three-dimensional (3D) tissues with a very precise and highly resolutive technology assisted by laser that helps to position different cell types in a 3D environment. The 4th dimension is the necessary maturation time for printed cells in different layers to become a functional and self-organized tissue. The 4D bioprinting approach consists of programming tissue self-organization by designing tissue-constituent organizations — cells and extracellular matrix — that evolve in a controlled way until specific biological functions emerge.”

Animal Free? Brisson said that regulators around the world are keen to see development and evaluation of such models for in vitro testing purposes. Furthermore, such technologies “might be of interest to limit the use of animals” in preclinical research. When asked what would help encourage wider adoption of such models, he described “the diffusion of the technology itself: making the bioprinting process and systems user friendly, affordable, safe, and precise enough to address the issues of tissue engineering and manufacturing.”

Meanwhile, Canadian company Stemcell Technologies has signed an exclusive license agreement with Brigham and Women’s Hospital for the rights to commercialize technologies for generation of human pluripotent stem-cell–derived kidney organoids. Such miniature organs are potential research tools to replicate in vivo organ function in vitro, in this case to provide a framework for studying renal physiology, injury, and disease at distinct developmental stages.

“Organoids can be used in place of — or as a supplement to — animal models for preclinical research,” a Stemcell spokesperson told us. Such cell-based models, however, are not likely to fully replace animal models in the future, “but they do provide an alternative in many cases.”

Brain on a Dish? Speaking in a press tour of the Radboud University Medical Center in Nijmegen, The Netherlands, technician Jason Keller told journalists that animal models do not necessarily help companies determine drug efficiency. “There is a push right now to find platforms that will be more predictive than animal models,” he said. Keller’s team currently is working on a “brain-on-a-dish” model made from a donor’s stem cells. The concept is in testing with antiepilepsy drugs as part of an effort find a potential treatment for Dravet Syndrome (also known as severe myoclonic epilepsy of infancy), a rare genetic disease with no predictive tool currently available for drug developers.