Carolyn Bertozzi founded the field of Bioorthogonal chemistry – a set of chemical reactions that allow scientists to study cells without disrupting the normal biological process of the cells. The term “biorthogonal” was coined by Bertozzi herself and means “not interacting with biology.”
The field had its origins in Bertozzi’s early interest in glycosylation, the naturally occurring cellular process by which sugars show up in proteins or other molecules. Changes in sugar levels in cells are associated with cancer and other illnesses. Bertozzi sought a way to monitor glycosylation and measure it, without affecting a cell’s natural functions.
She developed a chemical reaction that adds a marker molecule to cell surface sugars, using reagents that react with one another but not with normally occurring cell surface molecules. Bertozzi’s team has used the reaction to attach tracers to sugar molecules on cell surfaces in mice. The sugars they targeted are produced in elevated amounts by cancer cells and by inflamed cells. This technique could potentially be used to attach tracers to diseased cells in human patients, allowing doctors to pinpoint the location of cancerous cells in the body, and has led to development of a targeted pharmaceutical that is now in clinical trials.
American Bertozzi shares this year’s Nobel Prize for Chemistry with K. Barry Sharpless, also American, and Danish scientist Morten Meldal, who were cited for their work on Click Chemistry. The field allows molecular building blocks to be snapped together, like Lego pieces, to create complex molecules with huge implications for pharmaceutical development, medicine and material sciences.
The three scientists’ findings build on one another and together have contributed to major advances in the global fight against cancer.
Developments in Oncology
Oncology is one of the most exciting areas of drug development and cancer drugs make up nearly 40% of the global pharma pipeline. Over the coming years, CIO expects important clinical data for several new classes of drugs, as well as continued progress with personalized cancer medicines.
As the way cancer is defined and treated has changed, oncologists increasingly think about it based on its molecular signature and genetic mutations rather than the specific organ it is found in.
The major development of the last decade has been the coming of age of targeted immuno-oncology, an approach that harnesses the body’s own immune system to fight cancer. These treatments offer the hope of more durable responses to treatment than conventional therapy and can have the additional benefit of significantly reduced side effects compared to traditional chemotherapy. This makes them ideal for use by earlier-stage patients or in combination with other drugs.
The first wave of this new generation of drugs, known as checkpoint inhibitors, have established themselves as the standard of care in many cancer types including lung cancer and melanoma. Further broadening their use into the adjuvant (postsurgery) and neo-adjuvant (pre-surgery) settings could open up new opportunities.
Checkpoint inhibitors do not work for all patients, and there remains a need for new treatments in many cancer types. The current cancer pipeline is incredibly broad with various approaches including new immuno-oncology drugs. Some of the approaches likely to be in focus for investors over the next few years include:
• LAG-3 (lymphocyte-activation gene 3) is an immunooncology approach that modulates the activity of checkpoint inhibitors and improves the ability of T-cells to attack tumor cells.
• TIGIT (a type of T-cell immuno-receptor) is another next-generation immuno-oncology target that could be relevant to multiple tumor types.
• SERDs (selective estrogen degraders). Standard treatment for hormone-receptor positive breast cancer is hormonal therapy (aromatase inhbitors) in combination with a CDK4/6 inhibitor such as Pfizer’s Ibrance or Novartis’ Kisqali. SERDs have the potential to replace the aromatase inhibitor backbone of these combination treatments, offering a cleaner side-effect profile, and potentially better efficacy.
• Antibody-drug conjugates (ADCs) combine a cytotoxic chemotherapy designed to kill cancer cells with an antibody designed to target key proteins in the cancer
cell of interest. This allows the drug to be precisely delivered to where it is needed, reducing unwanted exposure of the drug to normal cells.
• Bispecific antibodies. An alternative approach is to engineer an antibody capable of binding to two or more proteins—so-called bispecific antibodies. By binding to two sites and pulling them together, bispecifics can improve the immune system’s ability to fight tumors.
Oncology is the largest and fastest-growing area within the global pharma market. Since 2015, sales of oncology drugs have grown at a 13% annual rate from USD 100 billion to around USD 160 billion. Key drivers have been the rapid commercial success of checkpoint inhibitors —now one of the world’s largest single drug classes with sales of over USD 25 billion in 2020—but also the successful commercialization of other oncology drugs including PARP inhibitors (used to treat breast and ovarian cancer), CDK 4/6 inhibitors (breast cancer), and CD38 inhibitors for hematological cancers. Personalized therapies using modified T-cells (known as CAR-Ts) have reached the market for leukemia, lymphoma and multiple myeloma
CIO expects oncology sales to continue to outpace the broader pharma market, maintaining broadly similar growth rates over the next five years and putting it on track to approach USD 290 billion by 2025. The drug classes above will all continue to drive this growth in the near term, but we expect new classes to contribute increasingly to growth over time.
To read more about the therapies discussed, as well as details on CIO’s outlook on oncology as a longer term investment theme, as well as a discussion of risks, ask your financial advisor for a copy of the report: Oncology – Longer Term Investments: Update, published 12 August 2021. The report includes a reference list.
Main contributor: Wendy Mock
