Emerging Therapeutics

Controlling Glycosylation in Fusion Protein Manufacturing to Generate Potent Biobetters

The pipelines of pharmaceutical companies are full of biological drugs. Many of them are innovative therapeutic proteins, but a growing number represent biosimilars and biobetters (Figure 1) (1). Biobetters typically are defined as being “based on innovative biologics but with improved properties” (2). Their development benefits from known therapeutic approaches and mechanisms of action resulting in low risk, fast paths to the clinic and thus lower costs. Superiority is achieved through extended half-life (t1/2), improved efficacy, and reduced immunogenicity or…

Developments in Antibody–Drug Conjugates: A Discussion with Thomas Ryll of ImmunoGen

As a major class of emerging therapies, antibody-drug conjugates (ADCs) already have gained the attention of biopharmaceutical researchers and manufacturers because they combine both the precision of monoclonal antibodies and the potency of highly potent drug compounds. A few ADCs already have entered the market, but many more candidates are progressing through industry pipelines. Platform processes are not yet universal (and it remains to be seen whether they ever will be), but major ADC developers are establishing their own with…

Panel Discussion: Emerging Biotherapies and Their Manufacturing Challenges

At noon on Tuesday, 20 June 2017, BioProcess International presented a panel discussion as part of the “Emerging Therapies” session of its BPI Theater at the Biotechnology Innovation Organization’s annual convention in San Diego. Moderated by Patricia Seymour (senior consultant at BioProcess Technology Consultants), this panel comprised Holger Wesche (vice president of research at Harpoon Therapeutics), Richard Snyder (chief scientific officer of Brammer Bio), Marc Better (vice president of product sciences at Kite Pharma), and Paulo Carvalho (associate director of…

Specialized Outsourcing Services: Antibody–Drug Conjugates

Managing just the conjugation part of an antibody–drug conjugate (ADC) project can be a challenge. So when you consider all the component parts of an ADC, it is understandable why so many related activities are outsourced. At Piramal Grangemouth, we provide conjugation development and manufacturing services. Together with our sister sites in the United States and United Kingdom, we offer payload manufacture and fill–finish capability. The Grangemouth (UK) site has been involved in ADC conjugation services now for over 13…

Special Report on Antibody-Drug Conjugates: Technical Challenges and Opportunities

Among the emerging targeted therapies in biotechnology, antibody–drug conjugates (ADCs) hold a unique position. An ADC consists of a monoclonal antibody (MAb) with affinity to tumor cells, a cytotoxic small-molecule payload, and a linker connecting the two. Together the MAb, conjugation chemistry, and cytotoxin increase the complexity of ADCs several-fold relative to unmodified MAbs — and exponentially relative to chemotherapies. Viewing ADCs as hybrids of antibody- and chemotherapy-based cancer therapies is tempting. That description applies chemically and structurally, but ADCs’…

Outsourcing and Biomanufacturing Challenges for Emerging Therapies: A Roundtable Discussion at BIO 2016’s BPI Theater

The biopharmaceutical industry is increasingly interested in a range of emerging therapies. “We’re really starting to get beyond the monoclonal antibody,” said Patricia Seymour (senior consultant with BioProcess Technology Consultants) in her introduction to a lunchtime BPI Theater roundtable at the 2016 Biotechnology Industry Organization annual convention in San Francisco, CA, this past June. The discussion brought together three industry insiders for strategic outsourcing to talk about emerging biotherapies and their manufacturing challenges: Mark Angelino (senior vice president of pharmaceutical…

Emerging Platform Bioprocesses for Viral Vectors and Gene Therapies

Recent advances in molecular biology are expediting genomic sequencing to underpin precision medicine. Such progress is positioning gene and gene-modified cell therapy on the cusp of an extraordinary revolution in patient care for presently unmet medical needs — and a new therapeutic class that could rival monoclonal antibodies (MAbs) in importance. However, despite substantial strides made in clinical trials, the bioprocessing community is struggling to fulfill growing demands for biomanufacturing capacity to make gene and gene-modified cell therapies — including…

Automation of CAR-T Cell Adoptive Immunotherapy Bioprocessing: Technology Opportunities to Debottleneck Manufacturing

Continued clinical efficacy demonstrations of cell-based immunotherapies (iTx) such as chimeric antigen receptor T cell (CAR-T) therapies has made the prospect increasingly likely of an immunotherapy product achieving conditional market authorization in the short term. For example, Novartis and the University of Pennsylvania’s lead candidate (CTL019) for treating a range of hematological malignancies received breakthrough status from the US Food and Drug Administration (FDA) in 2014, permitting access to an expedited drug development pathway for high unmet medical needs (1).…

Uniting Small-Molecule and Biologic Drug Perspectives: Analytical Characterization and Regulatory Considerations for Antibody–Drug Conjugates

Cosponsored by CASSS (an international separation science society) and the US Food and Drug Administration (FDA), the January 2010 CMC Strategy Forum explored antibody–drug conjugates (ADCs), which are monoclonal antibodies (MAbs) coupled to cytotoxic agents. The ADC platform of products is being used more and more for clinical evaluation in oncology. More than a dozen companies are developing several types, including products conjugated with calicheamicin, auristatins, and maytansinoids. Such products use the specificity of a MAb to deliver a cytotoxic…

Fine-Tuning ADCs for Best-in-Class Therapeutics

Antibody–drug conjugates (ADCs) use the targeting ability of a monoclonal antibody (MAb) to deliver a highly biologically active drug to diseased cells while sparing healthy cells, creating potent and effective therapies. This emerging class of novel drugs currently focuses almost exclusively on cancer treatment. Two blockbuster ADCs — brentuximab vedotin (Adcetris from Seattle Genetics) for treatment of rare lymphomas and ado-trastuzumab emtansine (Kadcyla from Genentech/ Roche, manufactured by Lonza) for treatment of HER2-positive metastatic breast cancer — have improved treatment…