Feliza Mirasol is the science editor for 

Feliza Mirasol

Andrew Carnegie of Inaphaea BioLabs discusses the establishment of translational CROs and the role of PDCs in the drug discovery process.

A Look at Translational CROs and PDC Modeling (BIO 2024)

At this year’s BIO annual meeting, drug discovery and early phase analytics garner greater industry focus. Andrew Carnegie, PhD, head of Strategic Commercial Development, Inaphaea BioLabs, discussed some trends in the R&D analytical space and the advances being made to speed up the drug discovery process.

Carnegie explains that translational contract research organizations (CROs) aim to bring more clinically relevant humanized cell-based assays to the forefront early in the drug development pathway. Having clinically relevant data early on can help minimize the risk of failure of a compound/molecule in the preclinical and clinical stages of development, he notes.

“[A translational CRO] is really about providing design, input, and interpretation of results, in addition to just running the experiments, and sending a report based on the study,” Carnegie says. “We feel that better experimental design should lead to a more streamlined plan that is more efficient, and it provides our partners with better value for money. So, we're really looking at cutting down timelines and bringing more data points early on in the experiment so people can make decisions about their molecules early on, and hopefully be more successful in the preclinical and clinical stages.”

Carnegie also emphasizes that drug discovery is a challenging process with a low success rate of release of drugs. “Data suggests that poor prediction of efficacy remains the main cause of attrition and clinical failure. Around that, too, traditional drug discoveries relied on 2D cell cultures, often using non-human species, but animal disease models rarely reflect and represent the real causes, complexities, and phenotypes of human disease. This has really influenced a rise of 3D organoids and more clinically relevant, complex humanized cell models in paving the way for more accurate preclinical models that closely mirror human physiology and pathology,” he explains.

Thus, the humanization of the early phases of drug target validation has the potential to significantly improve how targets are validated for drug discovery, Carnegie adds. Among the tools now being used to humanize early phases of drug target validation are patient-derived cell (PDC) models. “The PDC is a primary cell culture, and it's established from the patient cancer cells, which were isolated directly from the tumor tissue or the patient body fluids. PDCs are maintained at a low-pass ID number, and result in a much higher clinical relevance than tumor cell lines. This really ties in with us wanting to bring humanized models earlier into the process to be more relevant and give more relevant clinical prediction and predictive data. The models are a great combination of accessibility and disease relevance,” he states.

Better early analytical work ultimately improves campaign success or the drug development process, Carnegie also emphasizes. “Our approach is to provide improved data by using more relevant 3D and hypoxia testing in disease-relevant systems, and bringing that [in] earlier … allows for more successful campaigns. [In addition], the kill-the-compound early approach is also very valid, allowing time and money to be better placed. So, with that early analytical R&D work, you can really get a [significant amount] of information upfront, [which] makes your decision easier on whether you'll take that molecule into preclinical and then into the clinic,” he remarks.

“PDCs are really the first step towards the true humanization of preclinical science and can be used to improve the translation of preclinical assets and enhance biological understanding,” Carnegie concludes.

Click the video above for the full interview. BIO 2024 is being held in San Diego, Calif., on June 3–6.

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Andrew Carnegie, head of Strategic Commercial Development at Inaphaea BioLabs, discusses the establishment of translational CROs and the role of PDC models in the drug discovery process.

Lee Cronin, founder and CEO of Chemify, discusses the combination of digital chemistry, robotics, and AI in the drug discovery space at BIO 2024.

The Intersection of Chemistry, Robotics, and AI in Drug Discovery (BIO 2024)

As BIO 2024 moves into full swing, Lee Cronin, founder and CEO of Chemify, a UK-based company specializing in building up digital chemistry for chemical research, discovery, and manufacturing, discusses how the combination of digital chemistry, robotics, and artificial intelligence (AI) are advancing the drug discovery space.

According to Cronin, the concept behind digital chemistry is to connect chemical reactions to synthesize molecules in standardized hardware, or in a standardized way. This involves “using a programming language so that we can very faithfully reproduce chemistry, on demand and also to a given quality,” Cronin states. The process of computation in digital chemistry is akin to running code on a computer, he emphasizes. “The concept of digital chemistry … is pioneering this ability to turn code into molecules reliably at scale, on demand, and also for the creation of quite complex molecules, and even APIs,” he adds.

The combination of programming language, robotic architecture, and the use of data and AI is creating a new approach to not just making molecules but discovering and doing process optimization, practically in one tool chain, Cronin explains. “What this means is that we should be able to go from the discovery process to dreaming up new molecules to then the optimization and scaling,” he says.

It is not necessarily easy to dream up a molecule 

 and then translate that into producing that molecule on demand because some aspects may not be worked out, or the yields might be low, or there may be other blocks, Cronin points out. “What Chemify has done is we've built a series of approaches that allow us to digitize chemical reactions and have them ready on demand—a bit like building blocks,” he states. This approach allows the user to pull a code and go from a chemical reaction A to B or from a chemical reaction A to D, depending on preference. “[This approach] allows you to go from your target that you dream of, to then work out what particular reactions you must do ahead of time, and, more importantly, allows you to restrict your search of chemical space when you're [early in the research process], when you're dreaming up new molecules to reactions you know how to do, [and] so this increases the speed that you can discover new molecules and make new molecules, and go through the cycle of design–make–test–analyze,” Cronin explains.

Of particular significance is that once a new molecule has been made, once the code has been established, that code can be reused and optimized to scale further down the line, Cronin points out. “You've got this programming language and these reactions and the robots that run it; [therefore], you're able to update your process continuously with the weight of the insights that you get,” he adds. With these chemical reaction insights, the data and methods can then be processed through AI, allowing for optimized yields, Cronin states.

View the video above for the full interview with Cronin. Cronin is speaking at the 

New Tools, New Times: Chemical and Structural AI for Drug Discovery

 panel at BIO 2024 in San Diego, Calif., which is being held June 3–6.

Lee Cronin, founder and CEO of Chemify, discusses the combination of digital chemistry, robotics, and AI in the drug discovery space.

Cell and Gene Therapy Catapult (CGT Catapult) and the Canadian Advanced Therapies Training Institute (CATTI) have developed a strategy that aligns training standards and assessment for the manufacture of advanced therapies. The organizations noted in a May 30, 2024 announcement that this strategy is an important first step toward building shared standards to facilitate access to a skilled workforce.

Advanced therapies are manufactured by highly trained personnel who are good manufacturing practice (GMP)-certified and who know how to operate in aseptic conditions. The current training and assessment for these personnel varies around the world, which makes it difficult for the workforce to relocate and for the industry to access global talent.

“This partnership marks a crucial step towards ensuring that our workforce is equipped with the highest level of expertise to meet industry demands. By setting these international standards, we aim to enhance the quality and safety of advanced therapies, ultimately benefiting patients worldwide,” said Vanessa Laflamme, CEO of CATTI, in the press release.

CATTI and the CGT Catapult first formed a collaboration in 2023 under which they aim to increase the levels of standardization in the training and assessment standards used in Canada and the United Kingdom. Since then, the organizations have aligned training materials and programs and have outlined a joint strategy that specifies which specific skills and competencies should be assessed. The goal is to establish a rigorous template that can then be applied across all manufacturing training materials and across various skill levels.

“By sharing expertise and working with CATTI, a leading provider of training for the advanced therapies industry, we have a valuable opportunity to enhance and standardize the training available to organizations and individuals. This builds on the efforts of the CGT Catapult to date and the investment we have made, alongside government, in developing a successful training program for the UK workforce. Together, we aim to ensure that our growing global sector is supported by a highly skilled workforce equipped with the latest knowledge and skills,” said Matthew Durdy, chief executive, CGT Catapult in the release.

CATTI also partnered with bioMérieux Canada in December 2023 to combine their capabilities to enhance workforce training in advanced therapies and the production of quality control solutions for the bio/pharmaceutical industry (1). Under this agreement, bioMérieux is responsible for deploying more than half a million dollars’ worth of analytical equipment and services in the CATTI training laboratory located at the University of Guelph in Ontario, Canada. The training under this collaboration will equip highly qualified, GMP-certified personnel who are qualified to work under aseptic conditions with the skills and knowledge to manufacture anticancer immunotherapies, cell and gene therapies, vaccines, and other biotherapeutic applications.

1. Canadian Advanced Therapies Training Institute. CATTI and bioMérieux Canada are Joining Forces to Support the Development of a Qualified Workforce in Advanced Therapies. Press Release, Dec. 7, 2023.

Articles

CGT Catapult and CATTI aim to standardize advanced therapy manufacturing with new aligned training standards.

CGT Catapult and CATTI Establish Shared Training Standards for Advanced Therapies

The Cell and Gene Therapy Catapult (CGT Catapult), a UK-based independent innovation and technology organization specializing in CGTs, announced on May 29, 2024 that it has teamed up with Cellular Origins, a TTP company focused on enabling scalable, cost-effective, and efficient cell and gene therapy (CGT) manufacturing, to establish a universal automated system for CGT manufacturing.

Under the partnership, the two parties will implement the physical and digital integration of existing bioprocessing equipment at CGT Catapult’s Manufacturing Innovation Centre (MIC) in Stevenage, UK. They plan to achieve this integration by combining Cellular Origins’ robotic platform, Constellation, with CGT Catapult’s expertise in good manufacturing practice (GMP) operations. The goal is to generate evidence of the benefits of automation in real-world applications and advance the understanding of how automation can address barriers to scaling up that have hindered progress in CGT manufacturing.

Cellular Origins stated in a company press release that “[t]he unique benefit of Constellation is universal automation that fluidically and digitally integrates a wide range of existing bioprocessing equipment, with minimal change to both the biological process and the bioprocessing equipment.” The company’s use of automated tube welding allows it to adapt to a process, consumables, and equipment, rather than the other way round. The company can adapt without the need to add new components or connectors, which would enable therapy developers to scale their respective CGT therapy for wider administration to patients without the delays and risk of needing to re-develop their respective manufacturing process, according to Cellular Origins in the press release.

The Constellation platform will be based at CGT Catapult’s Stevenage MIC in that organization’s digital and automation testbeds. GCT Catapult launched two new digital and automation testbeds on May 29 as well. According to CGT Catapult’s press release, “The modules will be among the first sandbox environments anywhere in the world that have been specifically designed with automation, digital, and robotic technologies for the cell and gene therapy industry. They will mirror GMP standards to ensure that the processes developed can be rapidly deployed into GMP-compliant facilities.”

In addition to being equipped with the Constellation platform, these first testbeds will offer access to autoloMATE, an advanced orchestration and manufacturing management software from Autolomous, a UK-based provider of cloud-based CGT software platforms, which will allow for a streamlined and data-driven workflow, according to the CGT Catapult press release.

“[W]e are delighted to announce this collaboration, enabling us to access [CGT Catapult’s] expertise and leverage the full potential of Constellation to revolutionize CGT manufacturing at scale. CGT Catapult’s experience in establishing GMP facilities and optimizing cell therapy manufacture is directly aligned with Cellular Origins’ mission to prove the impact automated manufacturing can have in transforming cell therapy production. Through this partnership, we will work to demonstrate an automated manufacturing approach that will provide a route for patients worldwide to access these life-saving therapies,” said Edwin Stone, PhD, CEO at Cellular Origins, in the release.

“Embracing automation is a key step that the cell and gene therapy industry must take to reduce costs, increase efficiency and meet the growing demand for advanced therapies,” said Matthew Durdy, chief executive at the CGT Catapult, in the release. “Through working with leading robotics and software experts such as Cellular Origins, we aim to develop new strategies that increase levels of automation. This will help our collaborators access the benefits of these technologies, help make advanced therapies more affordable to healthcare systems, and help more patients receive life changing therapies.”

CGT Catapult will implement Cellular Origins' robotic platform in its Stevenage, UK, site to establish automated CGT manufacturing.

CGT Catapult and Cellular Origins Team Up to Develop Automated CGT Manufacturing

Eli Lilly and Company (Lilly) announced on May 24, 2024 that it has raised its investment in its Lebanon, Ind., manufacturing site by $5.3 billion, more than doubling its overall investment from $3.7 billion previously to now $9 billion. The increased funds are intended to boost the company’s manufacturing capacity for APIs used in the production of Zepbound (tirzepatide) injection and Mounjaro (tirzepatide) injection, which are used to treat chronic diseases such as obesity and type 2 diabetes.

"Today's announcement tops the largest manufacturing investment in our company's history and, we believe, represents the single largest investment in synthetic medicine API manufacturing in [United States] history," said David A. Ricks, Lilly's chair and CEO, in a company press release. "This multi-site campus will make our latest medicines, including Zepbound and Mounjaro, support pipeline growth and leverage the latest technology and automation for maximum efficiency, safety, and quality control. Importantly, we are investing in our home state of Indiana, creating high-wage, advanced manufacturing, engineering, and science jobs for hundreds of current and future Hoosier families."

Lilly has invested more than $16 billion since 2020 to develop new manufacturing sites in the United States and Europe. Outside of Indiana, the company’s other new sites include Research Triangle Park and Concord, NC; Limerick, Ireland; and Alzey, Germany. The company has also separately invested an additional $1.2 billion to update existing manufacturing facilities in Indianapolis, and, in April 2024, it acquired an injectable manufacturing facility in Pleasant Prairie, Wis., from Nexus Pharmaceuticals (1). These manufacturing investments altogether total more than $18 billion, according to the company press release.

With the additional investment in the Lebanon site, Lilly expects that 200 full-time jobs will be added for highly skilled workers, including engineers, scientists, operating personnel and lab technicians. The company anticipates a roster of an estimated 900 full-time employees when the facility is fully operational. The Lebanon site is located within Indiana's LEAP Research and Innovation District.

Meanwhile, the state of Indiana plans to support Lilly's expansion project by partnering with the company on infrastructure solutions, such as road improvements, water, electric, and other utilities. The state will also support workforce development commitments and certain economic incentives related to the company's achievement of its investment and employment goals.

"Lilly's commitment to meeting the demand for our life-changing medicines goes beyond buildings and extends to improving education opportunities and upskilling a global workforce of the future," said Edgardo Hernandez, executive vice-president and president, Lilly Manufacturing Operations, in the press release. "Academia is a critical partner to both industry and government as we work together to advance innovation in our state and communities around the globe."

Lilly broke ground at the Lebanon site in 2023 and expects to begin production toward the end of 2026, with operations scaling up through 2028.

1. Eli Lilly and Company. Lilly Acquires New Injectable Medicine Manufacturing Facility from Nexus Pharmaceuticals. Press Release, April 22, 2024.

Lilly’s investment increase is intended to boost manufacturing capacity at its Lebanon, Ind., site for APIs used in the production of tirzepatide and other pipeline drug candidates.

Lilly Raises Investment in Indiana Site to $9 Billion to Expand API Manufacturing

Johnson & Johnson signed a definitive agreement to acquire a wholly owned subsidiary of Numab Therapeutics, a clinical-stage biotechnology company specializing in immunology and oncology therapeutics, in an approximately $1.25 billion all-cash transaction, Johnson & Johnson announced on May 28, 2024. Through the acquisition, Johnson & Johnson gains the global rights to NM26, a novel, investigational bispecific antibody being developed for atopic dermatitis (AD). The transaction is subject to regulatory clearance and other customary closing conditions and is expected to close in the second half of 2024. 

NM26 will soon enter Phase II studies. The bispecific antibody targets two clinically proven pathways in AD, interleukin 4 receptor (IL4R)-alpha subunit (IL-4Rα) and IL-31. AD is the most common inflammatory skin disease (1); it is known to be highly heterogeneous and is driven by different disease mechanisms in distinct patient subpopulations. IL-4Rα triggers T helper type 2 (Th2)-mediated skin inflammation (1) and IL-31 impacts skin itch and subsequent scratching (2), both of which worsen the disease. By targeting these two pathways, NM26 has the potential to transform the standard of care for AD and could also be effective in treating other inflammatory skin diseases in which Th2 inflammation and itch are prevalent, according to a company press release.

“To deliver durable, symptom-free remission for the millions of people living with AD, our medicines need to be tailored to target multiple disease-driving pathways in different patient subpopulations,” said David Lee, Global Immunology Therapeutic Area head, Johnson & Johnson Innovative Medicine, in the press release. “That’s why we are committed to developing differentiated bispecifics that combine the targeting of two distinct disease-driving pathways. NM26 has the potential to deliver a treatment specifically for patients who have inflamed skin associated with intense itching.”

AD symptoms include inflamed skin that can be associated with itch and subsequent scratching, which often results in skin pain, skin abrasions that increase risk of infection, difficulty sleeping, anxiety, stress, depression, and in some cases an increased risk of suicide. “Current therapies fall short of delivering durable, symptom-free remission, with approximately 70% of patients not achieving remission in what is the most common inflammatory skin disease (1),” Johnson & Johnson cited in the press release.

“Our goal is to deliver transformational efficacy for all patients living with immune mediated diseases [such as] AD,” said Candice Long, worldwide vice-president, Immunology, Johnson & Johnson, in the release. “Our investment in differentiated bispecifics is the next chapter in our impactful Immunology legacy. It reinforces our commitment to address unmet medical needs by leveraging patient insights and our deep disease expertise.”

1. Simpson, E. L.; Bieber, T.; Guttman-Yassky, E.; et al. Two Phase 3 Trials of Dupilumab versus Placebo in Atopic Dermatitis. 

 (24), 2335–2348. DOI: 10.1056/NEJMoa1610020
2. Kabashima, K.; Matsumura, T.; Komazaki, H.; Kawashima, M. Nemolizumab Plus Topical Agents in Patients with Atopic Dermatitis (AD) and Moderate‐to‐Severe Pruritus Provide Improvement in Pruritus and Signs of AD for Up to 68 Weeks: Results from Two Phase III, Long‐Term Studies. 

Johnson & Johnson will gain NM26, a bispecific antibody targeting atopic dermatitis, via the acquisition of a wholly owned subsidiary of Numab Therapeutics.  