On the 6th – 9th July 2021 Oxford Global held Immuno Week: Online. Running over 4 days, the digital event showcased a range of industry-leading keynotes, 10+ panel discussions, Q+As, and workshops, as well as 40+ presentations and case studies. The flagship conference had 350 + delegates from the foremost pharmaceutical and biotech companies, as well as the top research institutions and provided an in-depth look at the key opportunities and challenges in cancer immunotherapy development from discovery through to the clinic. Key speakers included Marta Amaral (Laboratory Head at Sanofi), David Gilham (Chief Scientific Officer at Celyad), Pelin Candarlioglu (Cell Biologist-Bioengineer at GlaxoSmithKline), Klaus Dembowsky (Chief Executive Officer at amcure), Peter Ellmark (Chief Scientific at Officer at Alligator Bio), Philip Bland-Ward (Chief Development Officer at Crescendo Biologic), and Jens Kringelum (Director at Evaxion). In the post-event report, we have gathered some highlights from the event, including a summary of the key topic areas discussed in our post-event advisory board meeting, as well as the major trends and challenges facing the immunotherapy industry today.
The Event – Key Topic Areas
Immuno Week featured 4 in-depth conference days, each with a different thematic focus crucial to the immuno-oncology industry. On Day One, the spotlight was on Novel Therapeutic Modalities, with thematic sessions focussing on the discovery and development of innovative cell therapies and therapeutic antibodies. The most popular presentation with 85 views was the keynote address given by Celyad Oncology’s Chief Scientific Officer. Entitled, ‘Next-Generation Allogeneic And Autologous CAR T Candidates’, the presentation explored the process by which adoptive cell therapy for cancer arrived into the mainstream clinical conscience, as well the implications allogeneic and autologous CAR T candidates have for personalised medicine. The second most viewed presentation was the closing keynote presentation ‘Road Maps For Successful Tumour Immunotherapy’, led by the President and Chief Scientific Officer at Aleta Biotherapeutic. This talk provided an in-depth look at the latest novel therapeutics latest novel therapeutics modalities and combination therapies in cancer treatment and received 68 views.
Day Two covered Novel Biomarker in Immuno-Oncology, delving into the pressing considerations of identifying key biomarkers to improve patient response and enable precision immunotherapies, as well as genomic strategies for oncology. The keynote address presented by the Director of Genomic Immuno-Oncology at Evaxion was the most viewed presentation of the day. Entitled ‘AI & ML For Precision Immunotherapy’ the address received 60 views and introduced PIONEER, an automatic system for identification of cancer-specific epitopes. The Second most viewed talk was Simcere Pharmaceutical Group’s ‘Unleashing T Cell Activity By Targeting TNFR2 To Promote Robust Anti-Tumour Immunity’. The presentation received 52 views and spoke of the promising IO target, TNFR2, and its ability to reduce the proliferation and function of Treg cells.
Day Three provided an in-depth look at Advanced Models and Immunoassays, reflecting the continued industry focus on developing more accurate preclinical models within immuno-oncology. This stream showcased numerous case studies on preclinical models of safety and efficacy, such as 3D, in-vivo, and in-vitro models. The workshop entitled ‘Safety and Testing Immunotherapies In-Vitro’ was the most popular presentation of the day. It received a total of 58 views and consisted of 3 presentations, each led by a senior representative from GlaxoSmithKline, Roche Pharma Research and Early Development, and the University of Cambridge, followed by a panel discussion. The second most viewed presentation was led by the Vice President of WuXi AppTec, and looked at ‘Target Selection To In-Vivo Efficacy: Building An Integrated Immuno-Oncology Discovery Platform’. This investigated the use of humanised and advanced models for target identification and validation and received 56 views.
Finally, Day Four concluded the event with an afternoon workshop on Macrophage Drug Development. Pathios Therapeutics’ keynote address, ‘GPR65 Is A Critical Innate Immune Checkpoint In Tumour Associated Macrophages: Human Genetic Validation And Discovery Of Potent And Selective GPR65 Antagonists’, was the most popular event of the session with 45 views. In this, the Chief Executive Officer spoke of the correlation between tumour-associated macrophages and poor prognosis, and the innovative ways to overcome this. With 33 views, the second most popular presentation of Day 4 was Faron Pharmaceuticals’. Entitled ‘Macrophage Scavenger Receptors As Targets For Anti-Tumour Immunity’, the company’s Chief Development Officer discussed the promising early results of tumour targeting using macrophages.
Market Trends: Advanced Models, Tumour Microenvironment, and Combination Strategies
Since the approval of several checkpoint inhibitors in the early to mid-2010s, the global immunotherapy market has experienced rapid growth. Since 2017, the market has undergone a CAGR of 17.4%, growing from $33.7 billion to an estimated $103.4 billion by 2024. During the post-event advisory meeting, board members from both top biotech companies, and research institutions discussed the expected key market trends facing the immunotherapy industry today.
1.) Advancing Preclinical Models: Developing suitable models during the preclinical stage of immuno-oncology discovery and development is crucial. Immunotherapy requires advanced models that accurately simulate the complexity and diversity in the relationship between the body’s immune system and its ability to eliminate cancer cells. A common in-vivo model employed in preclinical trials is the use of mouse models. This approach enables the measurement of tumour growth via the physical measurement of tumour volume. However, despite its ease and speed of application, animal models such as mice rarely represent the intricacies and heterogeneity of human oncological diseases. As such, the field is experiencing a push towards developing more accurate preclinical models to better monitor drug activity, therapeutic response, and guide the development of safer and more effective therapies. In particular, there has been a significant drive towards more accurate preclinical models such as humanised mouse models and 3-D models.
2.) Investigating the Tumour Microenvironment: Understanding the functional role and contribution of the tumour microenvironment in cancer development is also an expanding area of immuno-oncology research. The microenvironment consists of stromal cells, extracellular matrix components, and nurtures the harsh environment needed for tumour growth. Cancer cells and their dynamic interactions with their microenvironment is an essential constituent in not only the disease progression but also drug resistance, the restraint of growth, and invasion and metastasis. Therefore, comprehension of the communication process occurring between cancer cells and the microenvironment provides a valuable insight into improving therapeutic responses. As a mechanism of interaction between cancer cells and their ability to evade immune surveillance, microenvironments may well provide the key to advancing immuno-oncology treatments – and might even facilitate the targeting of solid tumours, which have proven tricky to treat with immunotherapies up until this point.
3.) Improved Patient Response Using Combination Strategies: A major priority right now for immuno-oncology is the use of combination strategies to improve both patient response and the durability of treatments. While immunotherapy agents can be effective as a monotherapy option, combination therapies have the potential to reach a wider range of patients. Combination strategies act synergistically, with either immunotherapy agents being paired with conventional cancer treatments such as targeted therapy and radiotherapy, or by pairing two immunotherapy treatments together. These possess the complementary effects, which essentially provides a doubly powerful means of defence against an immune system attack. Exciting developments in the use of combination strategies to improve patient response includes findings from a UCL -led phase II trial. According to early results, a combination of the antibody therapeutics nivolumb and ipilmumab has provided the most optimal response to the treatment of metastatic prostate cancer to date.
Challenges: Safety, Significant Biomarkers, and Cost
With all the excitement surrounding the latest preclinical and clinical trials in immunotherapy, there are still a number of challenges to overcome before immuno-oncology becomes the therapeutic cornerstone in cancer care that scientists are predicting.
1.) Safety: While the successes of novel immuno-oncology therapies are undeniable, the safety of these treatments remains questionable. In some cases, their desired immune activation and pharmacological potency can lead to exaggerated effects and toxicity. Clinical trials have also found that cell and genes therapies in immuno-oncology can lead to immune system dysfunction, and as such can impair the humoral and cellular immunity the body requires to defend against certain infectious diseases. Unnecessary tissue damage can also occur, resulting in hypersensitivity and chronic inflammation. Industry response includes improving the safety of immuno-oncology through delivery technology. One such way is to take a systemic and localized delivery approach to mitigate the side-effects of immunotoxicity.
2.) Identifying Significant Biomarkers: Developing robust and validated biomarkers to monitor drug activity and therapeutic response is paramount to ensuring the guided development of safer and more effective therapies. Ensuring a high level of biomarker quality that uses validated and cutting-edge techniques is paramount. However, doing so presents numerous challenges. Firstly, the dynamic nature of the immune system makes it difficult to identify and then determine the effectivity of the biomarker candidate. Secondly, small patient target populations make it difficult to test the validity of the biomarker. One of many approaches to identifying significant biomarkers has included recent studies into the promise of Cancer Testis Antigens (CTAs). The attractive qualities of the potential biomarker CTAs includes their broad expression in a variety of cancers, effective immunogenicity, and a highly selective expression in tumour tissue.
3.) Reducing the Cost of Therapies: Despite the ground-breaking promise of many immunological therapies to date, the agents are extremely expensive to manufacture and administer. On average it can cost over $80 billion USD worldwide to treat selected cancers with immune blockers for a year. Consequently, these costs can put a huge strain on health care systems and can affect the reimbursement scheme of a country. Precision immunotherapy strategies also come with a heavy price tag. Given the nature of precision medicines, the extra level of personalisation to a patient or patient group inflates costs from a standard drug treatment. The requirement for genetic testing and companion diagnostics comes with a need for larger patient pools and elevated expenses.
Immuno-oncology is an area of intensive research and an incredibly competitive field. Since the approval of the first immuno-oncology therapeutic back in 2010, each year sees the approval of more drugs across multiple cancer types and partnering deals between leading pharmaceutical companies happen nearly every day, bringing us ever the closer to discovering the innovative and optimal therapeutic strategies needed to help defeat cancer once and for all. The future looks bright for immuno-oncology and here at Oxford Global we firmly believe it is set to become one of the integral pillars of cutting-edge cancer.
The market trends and the important insights provided by the advisory board will inform the structure and content of our 2022 Immuno series with the launch of our Preclinical Immuno-Oncology online event and our Tumour Microenvironment online event. Stay tuned for further information but in the meantime, we hope you can join us at the Immuno UK: In-Person event on the 13th and 14th October 2021.