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    what will therapy look like in 2033?


    For our special newsletter on cancer, Labiotech had the opportunity to put the same question to several biotech company experts. And while no one can know for sure what the future holds, the CEOs, CMOs and CSOs have some insightful comments on what cancer treatment will look like 10 years from now.

    Klaas Zuideveld, CEO, Versameb

    In 10 years from now, I expect cancer therapies to address the tumor in a fully-integrated system biological manner. The last 10 years have seen great advances in both combination therapies, as well as cancer diagnostics, in a next phase rather than combining therapies empirically or based on SoC (standard of care), a better understanding of an individual’s tumor biology should allow for an optimized approach where every element of a therapy targets a particular pathway in a synergistic manner to effectively eliminate the tumor.

    Ian Wilson, CEO, ImaginAb

    In his first major address to Congress in April 2021, President Joe Biden asked lawmakers to help him “end cancer as we know it.” The U.S.’ ambition to stop cancer deaths began with the project Moonshot. This program involves: 1. Include more people in expanded and modernized cancer clinical trials. 2. Increase the pipeline of new cancer drugs. 3. Ensure access to current and new standards of cancer care. 4. Enhance diversity in the cancer research workforce.

    We all expect that improvement in diagnosis will provide an opportunity to treat earlier and more effectively, and with this many new therapy modalities will emerge and be positioned throughout the cancer care path. Of particular note and of interest is the emergence of radiopharmaceutical therapy (RPT), fueled by the excitement of recently approved drugs such as Novartis Pluvicto approved by FDA as first targeted radioligand therapy for treatment of progressive, PSMA positive metastatic castration-resistant prostate cancer. 

    RPT is emerging as a safe and effective targeted approach to treating many types of cancer. In RPT, radiation is systemically or locally delivered using pharmaceuticals that either bind preferentially to cancer cells or accumulate by physiological mechanisms. Unlike biologic therapy, it is far less dependent on an understanding of signaling pathways and on identifying agents that interrupt the putative cancer phenotype-driving pathway (or pathways).

    The idea of linking a cancer-targeting molecule with a molecule that kills cancer cells is not new either. For example, several drugs called antibody-drug conjugates ADCs, in which an antibody that binds to specific cancer cells is linked to a toxic drug, have been approved for treating cancer. Many of these newer drugs are re-engineered versions of existing compounds used for nuclear imaging.

    Nuclear imaging tests, such as positron emission tomography (PET), sometimes use weakly radioactive compounds linked to molecules that bind to specific targets on the surface of cancer cells. Specialized cameras can then reveal even tiny deposits of cancer cells, helping to measure the spread of cancer through the body. And a big advantage of having imaging and treatment molecules that use the same target is that imaging can then give doctors a sneak preview of whether the treatment is likely to work.

    Kees Melief, CSO, ISA Pharmaceuticals

    Immunotherapy will have been further developed, including personalized vaccines and combination of therapeutic vaccines with immune checkpoint inhibitors and targeted drugs. In addition, adoptive T cell therapy and therapeutic vaccine combinations will have been developed and commercially established. Neoadjuvant immunotherapy will be approved and applied on a large scale, minimizing the risks of surgery on bulky cancers.

    John Maher, CSO, Leucid

    In gazing into the future, I look back over the past 20 years in which we have witnessed the emergence of a brand-new form of cancer treatment, namely immunotherapy.

    Immunotherapy was practiced unsuccessfully throughout the 20th century and even earlier and its repeated failure had caused it to become a laughing stock within the oncology community. That perspective has radically altered in the new millennium and I envision several further advances that will cement the mainstream role of cancer immunotherapy by the mid 2030s.

    The spectrum of tumor targets against which drugs may be directed using immunological approaches continues to increase through basic discovery research. This expanding list will undoubtedly be exploited using new immune cell engagers and antibody-drug conjugates with increasingly potent and precisely released toxic payloads.

    Immune checkpoint blockade has already uncovered a complex dialogue between the immune system and common cancers of which we had been completely oblivious. Building on this, we are likely to see the emergence of new agents that block additional physical, chemical and biological immune checkpoints operating within the microenvironment of common solid tumors.

    Within this burgeoning field, the area where I feel greatest impact will ultimately be achieved involves cellular immunotherapy. Therapeutically infused cells constitute living drugs with multiple anti-cancer attributes and they are amenable to sophisticated engineering strategies to achieve precise, targeted and controlled attack against tumors. In the same way as the mobile phones of 10 years ago provided only a small glimpse of the functionality of their modern-day successors, cellular therapies of the 2030s are likely to offer a further step change in therapeutic impact.

    The vanguard of this effort entails the engineering of immune cells to express CARs (chimeric antigen receptors), an approach that has achieved unprecedented clinical impact against blood cancers. While solid tumors impose many additional hurdles, the expanding toolbox of cellular and genetic engineering technologies offers tremendous scope for the further development and refinement of these therapies.

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    We are also learning of the need to carefully calibrate the activity of these cells to reduce acute toxicity and instead achieve a more durable and sustained assault on tumor deposits.

    This is a completely new way to treat cancer and will require considerable infrastructural innovation to enable scalable manufacture and delivery of these complex drugs to patients. As the field advances, cancer physicians will transition to become a new cadre of clinical immunologists as they grapple to harness the enormous potential of the immune system to control cancer as well as dealing with the immunopathology that accompanies these new therapies.

    Of course, this also means that future cancer doctors will need much greater immunology education than has been the case in typical medical school curricula!

    Will West, CEO, CellCentric

    The progress over the last decade has been amazing.  There is no reason why this won’t continue.  We will never ‘cure’ cancer, but we can certainly prevent more cases, and keep people alive for longer, and healthier.

    Catherine Pickering, CEO, iOnctura

    We will see an acceleration in the shift towards personalized cancer care.  The costs of profiling a tumor e.g. understanding the complete nature of all genetic mutations in the tumor, has decreased substantially in recent years.  In 10 years time, this targeted approach will drive cancer care across the majority of tumor types.

    There will be a bigger role for combination therapy.  We have learnt so much in recent years about how and why tumors respond to certain therapies.  Combinations of drugs that target multiple independent hallmarks of cancer have synergistic effects working together to prevent tumor cell proliferation whilst at the same time breaking down the tumor microenvironment to allow drugs to have better access to the tumor and unveiling the cancer to the immune system.  Combinations of tolerable drugs will be used to drive better patient outcomes.

    Jennifer Wheeler, CMO, Precirix

    First, it is helpful to take a look back – from a “one size fits all” treatment paradigm that was the norm a decade ago, towards an “n-of-one” approach where optimal treatment is based on the unique molecular characteristics of a patient’s tumor, immune system/tumor microenvironment (as well as other “omic” analytics). 

    There has been a revolution over the past decade towards personalized oncology.  This accelerated progress in the treatment of cancer has been supported by discoveries in other fields: bioinformatic and AI-driven approaches for interpretation of large datasets; internet-driven information access for broad collaborations and open access to research and resources; private funding for research and development leading to the approval of many new classes of oncology drugs beyond the traditional arsenal of chemotherapy drugs, among others.

    It seems reasonable to project even more accelerated improvements in the treatment of cancer over the coming decade.  In 10 years, it may be possible not only to detect cancer before visible tumors have formed, but to also treat with early intervention and prevent further development. 

    There will still be many patients diagnosed with advanced cancers.  The equitable dissemination of novel diagnostics and treatments to all patients may lag behind successful development and approvals, and patients without access will be more likely to present with advanced cancers. 

    Treatments for patients with “incurable,” advanced or metastatic cancers will be highly personalized and consist of combination approaches or multimodality, integrated platform therapeutics.  Cancer will be thought of as a “chronic disease” model, much like we think of diabetes and high blood pressure today, where sequential treatments are given over a lifetime after a diagnosis (though treatment of these diseases too will evolve significantly, and lifetime treatment may be less necessary).  Successful treatment of cancer patients with advanced disease will include an understanding of not only the patient’s tumor (with a broad “omic” understanding based on genomics, epigenomics, transcriptomics, proteomics and metabolomics) and tumor immune microenvironment, but also a multi-disciplinary approach of understanding misalignment and “disease” in other areas of the body and impact on cancer.  

    High throughput platforms that rapidly analyze patient samples and data, scaled to be used in large populations, will support an integrated, systems approach to the diagnosis and treatment of cancer.  One can imagine a future where a sample of a patient’s tumor is taken and rapidly analyzed with results that are rapidly integrated using an AI-driven algorithm.

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    There may be a 3D image of the tumor, down to the contours and pockets of cancer cell proteins, and including a topographic map of the immune landscape surrounding the tumor cells.  All feeding a real-time design of a molecule that is created to match the unique characteristics of the patient – molecular alterations, potential resistance pathways, etc.

    This “sci-fi” vision of bedside diagnosis and design of therapy may be a bit further off than 10 years, but it illustrates one of the important objectives – earlier detection and treatment personalized for each patient. And to go one step further, one can imagine that therapies will be “driven” by microscopic “bots” AI-powered to make real-time decisions based on data and analytics they feedback after dosing. 

    Radiopharmaceuticals, drugs that deliver potent radioactive isotopes directly to tumors, are likely to become an treatment modality across tumor types and stages of disease including: after tumors have already spread beyond the organ where they initially grew (advanced/metastatic, stage IV cancer) to decrease the size, and to control subsequent tumor growth; when metastatic tumors that have been treated successfully but start to grow again, to be able to treat on an intermittent, repeated basis to ensure control of disease (“maintenance” therapy); when a tumor is very large, to decrease the size and a make the tumor operable (“neoadjuvant” treatment); after surgery to decrease the chance that the cancer will come back (“adjuvant” treatment).    

    Radiopharmaceutical therapies will evolve into next generation theranostics that are even more precise with less toxicities, making it viable to retreat patients, and to consider treatment in the very early stages of disease.



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