ANTIBODY DRUG CONJUGATES ANTIBODY DRUG CONJUGATES Walk-in Hood fitted with a mobile reactor. ADC Clean Room (Class C area) Antibody Drug Conjugates (ADCs) are the combination of a monoclonal antibody (mAb) with a cell-killing cytotoxic drug. The antibody acts as a delivery system and selectively targets the tumour cells, due to its high binding specificity for tumourspecific antigens. Once the antibody has reached the tumour, it enters the cancer cell by endocytosis and releases its cytotoxic payload by chemical or enzymatic processes, eventually leading to the death of the targeted cell. The drug conjugate can also act as vascular-targeting agent and selectively attack the blood vessels of the cancer leading to the tumour’s necrosis after the rapid shutdown of its blood supply. The recent approvals of Adcetris® for Hodgkin’s lymphoma and Kadcyla® for Her2-positive breast cancer have provided further evidence of the potential of ADCs in the treatment of cancer. In addition, there are roughly 30 ADCs in clinical and 160 in preclinical development, so there is a need for high quality manufacturing to bring new products into the clinic and ultimately to the public. Autoclave and Hot Air Sterilizer in the ADC Clean Room (Class D area) The Three Main Components of an ADC: 1 The antibody, responsible for the pharmacokinetic and pharmacodynamics properties of the ADC. 2 The warhead accountable for the cell-killing potency. Typical warheads are cytotoxic payloads such highly potent tubulin inhibitors, DNA-alkylating agents or cross-linkers, as well as topoisomerase inhibitors. 3 The warhead linker, the position and the number of drug molecules loaded onto each antibody and the conjugation strategy. Warheads and Linkers Manufacture: Cytotoxic molecules are effective at a low dosage and are therefore classified as highly potent APIs. Because their occupational exposure limit (OEL) is in the low nano-gram range, they must be manufactured in dedicated engineeredbased containment facilities by highly trained personnel. CARBOGEN AMCIS offers highly potent development and manufacturing services since 2002. We are able to manufacture linkers and toxins, from laboratory scale for process research and development purposes up to large scale manufacturing on 1’600 L. Our containment facility has been recently qualified for OEL down to 10 ng/m3 OEL at 8-hour time weighted average. We operate at negative and positive pressure cascade (+30 Pa, +15 Pa, 0 Pa, -15 Pa) and in a dedicated ADC clean room with separated Grade D and C aseptic areas. Conjugation Strategies: Our dedicated team of chemists, biochemists and biologists can advise you on the best linker and conjugation strategy. We have practical experience with the most common conjugation. CARBOGEN AMCIS - Your Partner for Conjugation Projects CARBOGEN AMCIS can handle all aspects the ADC production with the exception of antibody manufacture. Conjugation Activities: Pioneers in the highly potent landscape, we successfully managed numerous drug-linker projects. Our first ADC project was in 2005 and since then it has been a growing interest from our customers, both large pharmaceutical companies and small biotech’s. •• Manipulation of biological molecules •• High potency services since 2002 •• Chemical modification with linkers and activators •• First ADC project in 2005 •• Conjugation of monoclonal antibodies to small molecule compounds up to 20 L volume (aqueous systems) •• Committed to safety •• OEL 10 ng/m3 8h-TWA •• Multiple drugs on the market and undergoing validation •• A septic environment with Grade D and C qualified areas •• Complete service offering for: •• cGMP Compliant •• Warheads, linkers and conjugation Purification & Analytics: •• Process development •• In-process monitoring by various means such as: UV/ Vis, HPLC, Endo-Safe, pH, capillary electrophoresis and conductivity •• Scale-up for drug conjugates •• ICH stability studies •• Full on-site analytical support for the release testing of the product: •• Enzyme Linked Immunosorbent Assay (ELISA) •• SDS-PAGE (Gel Electrophoresis) •• Outstanding track record •• Analytics and purification •• Fill-&-Finish capabilities •• Regulatory and CMC support •• Dedicated project management •• Tailored programmes based on your needs and budget •• Capillary Isoelectric Focusing (cIEF) •• Endotoxin analysis •• RP-HPLC (SEC, HIC, PLRP) TFF equipment in the ADC Clean Room (Class C area) Fill-&-Finish Capabilities In addition to our process research and manufacturing services for the fast supply of highly-potent APIs, CARBOGEN AMCIS offers formulation services for highly-potent drug products and GMP aseptic production of parenteral drugs, including cytostatics and cytotoxics. •• The native cysteine conjugation that exploits the solvent accessible inter-chain disulphide bonds of the antibody in the cysteine. •• Pre-clinical batches (for technical, stability or toxicology studies) •• The lysine conjugation technique uses the terminal amino group –NH2 of the lysine residue as conjugation site. •• Liquid forms, semi-solids and injectables •• The genetic modification approach genetically modifies the antibody sequence to display a functional group on pre-defined positions of the antibody. Why ADC at CARBOGEN AMCIS? •• Clinical batches (for phases I, II and III) GMP Lyophilisation •• Validation of aseptic processes (media fill testing) www.carbogen-amcis.com Bubendorf (Headquarters) CARBOGEN AMCIS AG Hauptstrasse 171 CH-4416 Bubendorf Switzerland www.carbogen-amcis.com CARBOGEN AMCIS AG is a leading service provider, offering a portfolio of drug-development and commercialization services to the pharmaceutical and biopharmaceutical industry at all stages of drug development. The integrated services provide innovative chemistry solutions to support timely and safe drug development allowing customers to make the best use of available resources. CARBOGEN (word), AMCIS (word), CARBOGEN AMCIS (word) and AC (logo) are trademarks owned or licensed by Dishman Pharma Solutions AG and all rights are reserved.