ORIGINALLY PUBLISHED:
12 December 2022
Written by:
Senior Vice President, Global Head of Haematology (Early and Late-Stage), Oncology R&D, AstraZeneca
Vice President, Global Franchise Head of Haematology, AstraZeneca
At AstraZeneca, our vision is to redefine the standards of care in haematology with innovative medicines and novel combination strategies.
By delivering a range of treatment options that address the complexity of blood cancers and reduce the treatment burden, we strive to ensure each patient receives the most effective and individualised care possible.
Addressing the Complexity of Blood Cancers
Despite advancements in haematology care, an estimated 4 million people globally live with blood cancer, underscoring the profound need for new treatments.1 The over 150 sub-types of blood cancers, including leukaemias, lymphomas, and myelomas, are complex and challenging to treat due to their molecular and phenotypic diversity.2 This complexity necessitates a range of therapeutic approaches, all underpinned by deep disease understanding.
Building New Standards of Care in Haematology
Our approach is driven by the knowledge that not all tumours are the same. Each type has a unique set of molecular drivers and requires treatments that address a patient's specific tumour characteristics.3 To this end, we are leveraging our leading discovery capabilities to advance a diverse and innovative portfolio, spanning antibody drug conjugates (ADCs), cell therapy, epigenetic modulating agents and T-cell engagers (TCEs).
We believe the real potential is in combining therapies to drive deeper, more durable responses, and the breadth of our haematology portfolio enables us to explore a range of novel combinations. A key focus is on developing chemo-free or chemo-light combinations that are administered over a short duration, as part of our commitment to reduce the treatment burden for patients.
As we strive to improve cure rates, it’s pivotal to identify and treat cancer early in the course of disease, or at the earliest signs of disease relapse. Together with our external partners, we are pioneering the use of cell-free DNA methods to assess minimal residual disease (MRD) as an intermediate clinical endpoint and to inform treatment decisions.
Advancing Our Haematology Pipeline of Next-Generation Modalities
Our approach to developing transformational medicines is two-fold:
- Leveraging mechanisms that kill cancer cells directly, for example by targeting tumour drivers or delivering chemotherapy into cancer cells
- Exploring ways to activate the immune system to better detect and eliminate cancer while sparing healthy cells
One area of focus is on modalities that generate a new immune response against cancer, including TCE and cell therapies. These treatments can expand the promise of immunotherapy to patients without existing immunity against their tumour and who are not expected to respond to current treatments.
T-Cell Engagers (TCEs)
TCEs are multispecific antibodies engineered to activate the patient’s own immune system against their tumour.4 While TCEs are driving meaningful impact across some types of blood cancer, side effects like cytokine release syndrome can limit the amount of drug administered.5 To address this we are exploring various approaches including step-up dosing methods to gradually prime the patient’s immune system.
We’ve also pioneered the Target Induced T-cell Activating Nanobody (TITAN) platform, and delivered our first next-generation TCE in haematology, targeting CD20, which preferentially engages the CD8 subpopulation of T-cells. Our new class of TCEs is designed to engage only the T-cells that can kill tumour cells, aiming to achieve a more targeted immune response against cancer.
Cell Therapy
Cell therapy holds great promise as a one-time-treatment in haematology care. Chimeric antigen receptor T-cells (CAR-Ts), a type of cell therapy created by isolating and modifying a patient’s T-cells to target their disease, have shown the ability to eradicate very advanced leukaemias and lymphomas and are having a significant impact in the treatment of some types of blood cancer.6
Building on this, we are progressing innovative solutions to overcome barriers to cell therapy adoption, such as the complex and long manufacturing process. Our dual-targeting CAR-T is designed using a rapid manufacturing technology that has the potential to bring cell therapy to patients faster. Looking ahead, we are researching ways to deliver off-the-shelf patient-ready cell therapies.
Antibody-Drug Conjugates (ADCs)
We are also exploring mechanisms that directly kill cancer cells. By harnessing the tumour-targeted ability of an antibody to deliver a chemotherapy agent into cancer cells, ADCs provide a selective way to kill cells and minimise damage to healthy cells. ADCs will have an important role to play in the future of haematology care, including as a backbone therapy for building novel combinations.
Our ambition to build new standards of care is bold. But that’s what makes coming to work at a place like AstraZeneca every day so exhilarating. We look forward to continuing to innovate and accelerate the discovery and development of transformative therapies for even more patients.
