Science Pool

Just - Evotec Biologics is at the forefront of biomanufacturing innovation with its JP3 platform. By integrating intensified perfusion cell culture and fully connected downstream processing, we achieve remarkable productivity and cost efficiency. Our approach not only boosts output but also ensures consistent, high-quality biotherapeutics.

Leveraging AI/ML technologies and advanced process intensification, Just - Evotec Biologics is setting new industry standards. Our continuous manufacturing process significantly reduces costs and expands global access to essential biotherapeutics.

Download

In the evolving landscape of cancer treatment, Immuno-Oncology (IO) has been at the forefront for the past 15 years, revolutionizing our approach to battling this formidable disease. Immunotherapy, which harnesses the body's immune system to fight cancer, offers hope where traditional therapies have often fallen short. For instance, in advanced stage IV melanoma, the median survival has improved from 6 months to 6 years over the past decade thanks to immunotherapy.

However, the journey from discovery to clinical application is fraught with challenges. Why do some patients respond to immunotherapy while others do not? What opportunities exist for developing the right combination therapies? How can we better select the right cancer indications for a particular IO target? How can we ensure the success of these treatments across diverse patient populations?

At Evotec, our immunologists are equipped with the expertise and experience to support your IO projects from target identification through to clinical trials. Whether you require a comprehensive and strategic partnership or targeted support at critical stages, our capabilities can synergize with your efforts to make a tangible difference.

Comprehensive Support Across the Immuno-Oncology Spectrum

In-depth Immunology Expertise

Our team’s knowledge spans from innate to adaptive immunity, providing a robust foundation for developing cutting-edge cancer immunotherapies. We offer:

●    Genetic Engineering of Primary Immune Cells: Optimizing target validation for effective therapy development.
●    Bespoke In Vitro Immunological Assays: Custom-designed assays to evaluate immune responses and the potency of immunotherapeutic candidates.
●    Single-Cell Level Immunotherapy Assessment: Utilizing Immunological Synapse technology for precise drug discovery.

Preclinical Animal Models Dedicated to IO

Moving forward with candidates within the drug discovery journey requires robust and tailored in vivo models for IO:
●    Syngeneic Mouse Models: Developed with various tumor-immune phenotypes and responsiveness to checkpoint inhibitors; these models help in assessing therapeutic efficacy, modulation of the immune response (tumor microenvironment and periphery), as well as pharmacodynamics features (PK/PD).
●    Humanized Mouse Models: Presenting a functional human immune system with the possibility of xenografting a human tumor. These models are pivotal for particular therapeutic modalities such as biologic therapeutics (e.g., immune cell engagers) or cell therapies; they could also be interesting for early toxicology studies looking at immune-related adverse events.

Translational Validation Using Relevant Patient Samples

To bridge the gap between in vitro models done with primary human immune cells isolated from healthy donors and in vivo models in the drug discovery process:
●    Broad Clinical Network: Collaborations with hospitals and clinicians to select the relevant samples for the project.
●    Translational Validation of Therapies: Access to cancer patient samples ensures that therapies are effective in a patient context.
●    Enhanced Target Validation: Possibility to develop on-target biomarker assays or validate target expression in a particular indication.

Advanced Technological Integration

Our approach integrates cutting-edge technologies to de-risk your drug development strategy:
●    High-Throughput Imaging and Analysis: Tools like the ImageStream X and Operetta provide high-speed, high-resolution insights into immune cell interactions.
●    Complex Flow-Cytometry and Functional Assays: These analyses on fresh human tumor samples facilitate target engagement validation and biomarker identification.
●    Omics Technologies: Including scRNAseq, TCR sequencing, and proteomics, to uncover novel biomarkers and therapeutic targets.

Precision Medicine and Biomarker Strategies

By incorporating biomarker strategies early in the discovery process, we enhance the understanding of disease mechanisms and improve patient stratification for clinical trials. Our efforts in precision medicine are aimed at identifying the right therapeutic interventions for the right patients, thereby increasing the likelihood of clinical success.

The Evotec Advantage

Evotec’s experienced IO team supports your projects from the lab bench to the patient bedside. Our comprehensive services include:
●    Functional In Vitro Immunological Assays: Supporting programs for small molecules, biologics, and cell therapies.
●    In Vivo Rodent Models: Essential for preclinical testing of therapeutic efficacy and safety.
●    Translational Research and Patient Sample Access: Enhancing the relevance and translatability of preclinical findings.

Driving Success in Immuno-Oncology

Our integrated approach, combining deep immunological expertise with advanced technologies and translational capabilities, ensures that we address the complex challenges of IO drug discovery. By partnering with Evotec, you gain access to a wealth of knowledge and resources designed to propel your project forward, from the initial stages of discovery to the clinical validation of novel therapies.
For more information on how Evotec can support your Immuno-Oncology projects, visit our website or contact us at info@evotec.com.

Conclusion

The revolution in cancer immunotherapy is just beginning, and the journey to effective treatments requires collaboration, innovation, and expertise. At Evotec, we are committed to advancing the field of Immuno-Oncology, providing the tools and support necessary to transform groundbreaking discoveries into life-saving therapies. Join us in this mission and let’s make a difference in the fight against cancer.
Contact us today to speak with one of our immunologists and explore how we can progress your IO projects together.

Learn More

In the dynamic world of biopharmaceuticals, cost efficiency is a critical factor, especially for start-up companies navigating the complex landscape of drug development. Continuous biomanufacturing is an innovative approach that has garnered significant attention for its potential to significantly reduce the cost of commercial biologics. Less often discussed, however, is the potential for continuous biomanufacturing platforms for first-in-human (FIH) clinical trials. This method not only streamlines the production process but also offers substantial savings during the manufacture of material intended for early phase antibody development, making it an attractive option for emerging biotech firms.

 

What is Continuous Biomanufacturing?

Continuous biomanufacturing is a process where the production of biopharmaceuticals occurs in a seamless, ongoing manner, as opposed to traditional batch manufacturing, which involves discrete, separate production cycles. This continuous approach leverages advanced technologies and automation to maintain a steady flow of production, ensuring consistent quality and efficiency.

 

Cost Efficiency in Early-Stage Clinical Trials

One of the most compelling advantages of continuous biomanufacturing is its ability to produce large quantities of biopharmaceuticals in a single run. This is particularly beneficial for early phase clinical trials, where the initial supply can often be enough to cover subsequent Phase 2a and Phase 2b clinical studies. Here’s why emerging biopharmaceutical companies benefit:

1. Elimination of Additional Batches: Traditional batch manufacturing often requires multiple production runs to meet the demands of Phase I and II clinical trials. Each additional batch incurs significant costs, including raw materials, labor, and quality control. Continuous biomanufacturing, however, can produce a large enough supply in one go, eliminating the need for these extra batches.
   
   
2. Consistent Quality: Continuous processes are designed to maintain a high level of consistency and offer more levers to tightly control critical quality attributes than fed-batch processes. Supplying multiple clinical trials from the same lot of material ensures a perfect level of consistency which is crucial for regulatory approval and patient safety, further streamlining the development process.
   
   
3. Time Savings: By producing all necessary material in one continuous run, companies can significantly reduce the overall time required to manufacture the material they need for clinical trials. They avoid the challenge of finding available slots in their CDMO’s production schedule. This accelerates the overall timeline for clinical trials, allowing for faster progression through the development pipeline.

 

Financial Impact for Start-Ups

For start-up companies, the financial implications of continuous biomanufacturing are profound. The cost savings from eliminating additional batches can amount to millions of dollars. These funds can then be redirected towards other critical areas of drug development, such as:

1. Research and Development: Investing in expanding the pipeline of new candidate biopharmaceuticals. 
   
   
2. Clinical Trials: Initiating additional clinical studies for other disease indications. 
   
   
3. Extending the funding runway: Providing the company with the longest possible time before it needs to raise additional funding. 
   
   

 

Learn More

Biopharmaceutical companies increasingly want to convert fed-batch manufacturing processes to continuous platforms. We teamed up with GLOBAL Regulatory Writing & Consulting for this whitepaper so that you can learn:

• How to meet regulatory expectations when switching to continuous manufacturing
• The importance of appropriate risk assessments
• How to demonstrate comparability with previously manufactured material

Learn More

Very Large-Scale (VLS) production facilities have traditionally been used for the commercial supply of biopharmaceuticals. Some commentators  argue that there is no need to break with this orthodoxy. Yet many sponsor companies and CDMOs are making a concerted effort to establish continuous drug substance manufacturing. In this blog article we examine six reasons that might explain this phenomenon.

 

Why are so many innovator companies and contract manufacturing organizations making a concerted effort to establish continuous drug substance bioprocesses? 

Historically the biopharmaceutical industry has relied on Very Large-Scale (VLS) production facilities for commercial supply. Yet there are increasingly frequent calls for innovation in antibody manufacturing¹ backed by industry consortia like NIIMBL² and the BioPhorum Operations Group³. Let’s explore some of the reasons why:

 

1. Productivity: Continuous manufacturing allows significantly higher productivity than fed-batch manufacturing in VLS facilities. The current state of the art for cell line development in fed-batch processes is 8+ g/L compared with equivalent titers of 30+ g/L in perfusion bioreactors⁴. This allows antibody production in smaller, more efficient and agile facilities that deliver extremely low Cost of Goods Manufactured (COGM) while avoiding upfront scale-up costs and risk⁴.

 

2. Production Capacity: Continuous manufacturing facilities, such as Just - Evotec Biologics J.POD^® facilities, can deliver 2,000+ kg of drug substance each year and are ideal for many biotherapeutics including monoclonals, bispecific antibodies and Fc-fusion proteins. VLS facilities are designed to accommodate a small number of high-volume products.

 

3. Agility: Demand for biologics fluctuate throughout their lifecycle and is notoriously difficult to predict. This is especially true during both the product introduction phase and at the end of the lifecycle as sales are eroded by competing products. 

Commercial demand for Enbrel^®, for example, was so great when it was launched that patients’ access was restricted until the supply chain recovered⁶. In contrast, Biogen started investing $2 billion in VLS manufacturing at Solothurn, Switzerland in 2015⁷ to manufacture Aduhelm^®. The product was initially approved in June 2021 only for the company to announce it would halt sales due to a realignment of its Alzheimer’s disease franchise in January 2024⁸ leaving the company to find a new use for their facility.

Continuous biomanufacturing facilities comprising of intensified single-use platforms with production-on-demand cleanrooms are extremely agile and can be built in under two years thanks to parallel construction techniques and reduced need for WFI, SIP and CIP utilities. This contrasts with stainless steel VLS facilities which take over 4 years to bring online⁹. They require significant amounts of capital engineering leading to high depreciation costs that must be ultimately borne by the facility occupants.

 

4. Supply Chain Security with Distributed Manufacturing: Global drug shortages have put the spotlight on supply chain security in the pharmaceutical industry. These have become vulnerable for several reasons including an over-reliance on small numbers of centralized facilities in a limited number of geographical regions¹⁰.

Global networks of distributed manufacturing facilities mitigate these risks and ensure the needs of local patient populations are met despite a range of scenarios that can evolve during epidemics and pandemics. This avoids an excessive reliance on non-governmental organizations corralling manufacturers to produce specific medicines or demanding elusive new business model solutions that may or may not expand access. With the aim of increasing medicine supply chain security for their population, policymakers such as the French government have chosen to invest in industrial sovereignty in the healthcare sector. The need for this was emphasised by the health crisis caused by the COVID-19 pandemic¹¹.

 

5. Process Portability: VLS production processes suffer from having low process portability. Transferring between these facilities is neither fast, inexpensive or assured of success. The cost of transferring processes into a new VLS facility runs into tens of millions of dollars. Consider the bill for new consumables alone or the cost of packing chromatography columns with diameters exceeding 1.4 m with Protein A resins. Very few VLS facilities are identical despite what commentators would like us to believe.

In practice, these fixed pipe facilities must be re-engineered for each new unique product that is transferred into the asset. The sponsor must pay these CAPEX costs but also the cost of pilot and engineering runs required to mitigate scale-up risks. 

Just – Evotec Biologics provide true process portability by offering partners access to its technology platform under a licensing agreement so that sponsor companies can bring their products and processes in-house and fully under their control.

 

6. Sustainability: Pharmaceutical and large biotechnology companies are increasingly cognizant of their environmental impact and are setting ambitious sustainability goals. Intensifying antibody production through adopting continuous manufacturing will allow these firms to manufacture their antibody products with fewer of the earth’s resources¹². In contrast, VLS facilities require large amounts of carbon-intensive concrete during their construction phase. During operations they need significant amounts of energy to generate super-heated steam for SIP systems and highly purified water-for-injection needed for flushing cleaning solutions from stainless steel tanks.

 

References

1. Kelley, B. (2024). The history and potential future of monoclonal antibody therapeutics development and manufacturing in four eras. mAbs, 16(1). https://doi.org/10.1080/19420862.2024.2373330
2. Process Intensification Program - NIIMBL
3. BioPhorum Technology Roadmapping roadmap vision 2.0
4. J.CHO High Expression System for Continuous Manufacturing with Extraordinary Titers - Science Pool (evotec.com)
5. Garcia, F.A. & Gefroh, E. (2023) Reducing biopharmaceutical manufacturing costs through continuous processing in a flexible J.POD® facility. Drug Discovery Today, 28 (7). https://doi.org/10.1016/j.drudis.2023.103619.
6. Gellene D. Immunex says enbrel shortage worse than anticipated [Internet]. Los Angeles Times; 2002. https://www.latimes.com/ archives/la-xpm-2002-may-24-fi-immunex24-story.html
7. Biogen, awaiting FDA nod for $2B Swiss plant, plans to ship initial Aduhelm doses from North Carolina factory | Fierce Pharma
8. Biogen: how is the biotech pivoting from a failed Alzheimer's drug? (labiotech.eu)
9. FUJIFILM DIOSYNTH BIOTECHNOLOGIES BREAKS GROUND ON THE LARGEST CELL CULTURE BIOPHARMACEUTICAL CDMO FACILITY IN NORTH AMERICA | Fujifilm [United States]
10. Four ways pharma companies can make their supply chains more resilient | McKinsey
11 Evotec accelerates access to biologic therapeutics with initiation of manufacturing facility in Toulouse - Evotec Website (English)
12. Continuous Biomanufacturing Reduces Environmental Impact - Science Pool (evotec.com)

 

Learn More

Download our presentation from Recovery of Biological Products XX titled “Turning the crank using a hybrid continuous purification platform” from Michelle Najera, Megan McClure, Shahbaz Gardezi and Beth Larimore. 

Learn how:

1. Process intensification solutions for monoclonal antibodies, Fc-fusion proteins and bispecific antibodies t ease liquid handling pain points.
2. Our J.CHO^TM High Expression System is delivering perfusion permeate titers of over 2 g/L/d over 25 days.
3. Continuous capture chromatography significantly enhances resin utilization
4. Two tank virus inactivation steps can be developed with bench-scale models

Download the Presentation

 

This poster describes the rapid conversion of an intensified fed-batch antibody manufacturing process to an integrated continuous biomanufacturing process using the Just-Evotec Biologics platform, resulting in several key project accomplishments: 

• Mitigation of upstream IFB challenges
• Significant productivity increase
• Short development time
• Minimal risk from changes in product quality

These results demonstrate that the rapid conversion of fed-batch processes for monoclonal antibodies to an integrated continuous biomanufacturing process can be achieved with a robust ICB platform. This supports the biotherapeutics industry’s need to quickly adapt to changing clinical and business circumstances.

Download our poster

Biologics manufacturing typically uses engineered Chinese Hamster Ovary (CHO) cells to produce folded and glycosylated antibodies. Determining the optimum conditions to grow and maintain cell culture often requires considerable time and effort.

A quantitative understanding of cell metabolism through an analysis of cell culture metabolites can enable optimization growth conditions for improved titles or increased perfusion duration. Mass spectrometry is the optimum tool for metabolite measurement, however, transforming raw data into accurate quantitative measurement requires both expertise and extensive sample preparation.

In this poster we demonstrate the ability of simple sample preparation using universal calibrators and a novel machine learning algorithm to rapidly provide biological insight into bioprocessing samples taken from perfusion cell cultures.

Download our poster

Continuous biomanufacturing is reducing the cost of goods of biopharmaceuticals. Achieving continuous manufacturing requires expertise in equipment design.

Download the highlights of Andrea Isby's presentation at Repligen's DSP Workshop in Estonia from May 23rd, 2024 to learn more. 

Download the presentation

High-throughput screening methodologies have accelerated downstream development for monoclonal antibodies by enabling parallelized evaluation of chromatographic resins across a range of conditions. However, scientists must now interpret results in a meaningful and consistent way.

Learn how Just - Evotec Biologics' Downstream Data Browser automates visualization of high-throughput datasets, fits response surface statistical models, standardizes report results from a high-throughput screening method and facilitates comparison across molecules allowing the accelerated development of continuous biomanufacturing processes.

Read our poster to learn more