24/7 BIOPHARMA - issue 1 / October 2024

INDENA

Indena has been continually investing in know-how, personnel and equipment for its CDMO services for many years. Its most recent expansion program includes the construction of a state-of-the-art new 400 sq m R&D laboratory equipped with high performance and high containment fumehoods (12 bench-top fumehoods and two walk-in fumehoods), a laminar flow fumehood, two gloveboxes able to host 15 R&D scientists, completing the team of 70 scientists working at Indena. A new industrial GMP line with reactors until 10 000L will also allow the company to produce and commercialise many more regular APIs and HPAPIs. The market for HPAPIs is growing due to the increasing prevalence of complex diseases and the development of targeted therapies. It has been estimated that HPAPIs may now account for more than 30% of the drug development pipeline. Some of the conditions that use HPAPIs include cancers, auto-immune disorders, infectious diseases and rare diseases. It can be said that Indena is at the forefront in addressing the latest market challenges, as its capability in HPAPIs production comes from the experience it gained more than 30 years ago, with the first oncological blockbuster drug, Paclitaxel. The production of Paclitaxel involved some challenges: the development of a sustainable supply chain for the ingredient; the development of a method of isolation under high-containment conditions; and the analytical methodology of control according to stringent pharmaceutical protocols in terms of purity and stability. The solution devised by Indena for Paclitaxel was an extraordinary result and created a unique expertise of the company – from its experience of working with nature, Indena has learned to manage complex molecules of any type, from both the analytical and the production perspectives. Today, Indena’s ambition is to extend its expertise also to Antibody Drug Conjugates (ADCs), which represent a significant advancement in targeted therapy, holding immense promise for the pharmaceutical industry. These engineered molecules combine the specificity of monoclonal antibodies with the potent cytotoxicity of chemotherapeutic drugs, offering a more precise and potentially less toxic approach. Indena is now able to manufacture linker-payload that means specifically: - Development and Clinical Supply batches: payload-linker process development, scale-up, Challenges of a growing market

Figure 1. Glovebox.

analytical development and preliminary non-GMP Bioconjugation trials. Scale: from 10 mg to 100g. - GMP Manufacturing: linker-payload clinical manufacturing and commercial manufacturing. Scale: from 50 g to 5 kg. - Outstanding analytical development capability. - Indena is already present on the market with some payloads such as: - Maytansinoids: DM1 & DM4 entirely manufactured in Europe at the Indena plant (including fermentation and synthesis steps). - CDMO linker-payload: Manufacturing of a GMP linker-payload in phase one. - Bioconjugation: ADC pre-clinical research – Bioconjugation trials. Since 2019, Indena’s main production site has been equipped with a GMP Pilot plant, which includes two 1000 L reactors in stainless steel, 400 and 1000 L glass lined reactors, 250 L hastelloy reactor, temperature ranges: -80 °C/+200 °C, 500 L chromatographic column and hastelloy centrifuge. The P8 plant is being expanded in several steps, starting from a first revamping in early 2024, then with further upgrades in late 2024/early 2025. This expansion will allow the plant to enlarge the capacity of reactions/ chemical synthesis up to ten times the actual capacity, produce on larger scale HPAPIs obtained both by State-of-the-art equipment

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TWENTYFOURSEVENBIOPHARMA Issue 1 / October 2024