IMMUNO-ONCOLOGY INSIGHTS

Anticipating immuno-oncology modality/platform development trends for 2022

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Anticipating immuno-oncology modality/platform development trends for 2022

Tumor-mediated immune suppression: beyond PD-1
- What next for TIGIT and LAG-3? (And will further checkpoint inhibitor opportunities arise?)
- Exploring various mechanisms and their future relevance to the I-O field (eg. TGF-β)
Examining the near-mid-term prospects and development trends for next-generation cellular immunotherapy
- How is the new wave of autologous CAR T cell immunotherapies set to build on the clinical success of first and second generation approaches?
- Allogeneic cellular immunotherapy – how are safety and efficacy obstacles being addressed in early clinical studies (eg. through gene editing)?
- What progress in engaging and harnessing innate immune system mechanisms against solid tumors? (eg. NK cells, γδ T cells, , TLR or STING agonists)
- Next-gen CARs (eg. TRUCKS and multi-targeted CARs, CAR macrophages)
Are cancer vaccines back to stay? Assessing progress in alleviating long-standing delivery and target selection challenges
- Personalized neoantigen-based cancer vaccines
Oncolytic virotherapy: How are various platforms and payloads stacking up?
- What might the future combination therapy picture look like?
- How to leverage in patients with systemic metastatic disease?
A pivotal year for bi-/tri-specific T cell engagers: are novel targets resulting in reduced toxicity and enhanced T cell activation in the clinic/against solid tumors?
Cytokines: next steps in the development and I-O application of IL-2, IL-15, IL-18, etc.

Dissecting investor and market access trends and drivers for I-O R&D insights

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Dissecting investor and market access trends and drivers for I-O R&D insights

What are investors’ and analysts’ reflections on current vibrant market sentiment and associated VC/IPO activity, and their expectations for future financing trends in the I-O space? And what is their message for industry decision-makers?
How will the market evaluate larger (but crowded) indications vs niche indications for I-O agents moving forward?
What are the implications for patients, clinicians, regulators, and the field as a whole of recent I-O product withdrawals following conditional approvals?
Mounting competition in the PD-1/PD-L1 arena: what will be the repercussions for:
- Checkpoint inhibitor pricing and reimbursement? (Will we see a price war? What does that mean for the I-O industry, if so?)
  - When will we see the first PD-1 biosimilar? What will be its expected impact?
- Combination therapy development strategy across the I-O sector?
What novel/innovative pricing and reimbursement models are best suited to next-generation I-O therapeutics, particularly as they move into earlier lines of therapy? (Eg. pay by performance models)
How can the community as a whole work to increase patient access to I-O therapeutics on a global basis?

Optimizing clinical development strategy for the rapidly evolving I-O field

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Optimizing clinical development strategy for the rapidly evolving I-O field

Expanding the reach of immuno-oncology
- Examining novel clinical trial endpoints in I-O studies – what’s being considered across the field? Developers and regulator perspectives
- Examining clinical development strategies and data for I-O agents in earlier lines of treatment/stages of disease – what lessons can the field take moving forward?
  - What does data obtained so far tell us about future I-O applications in the neoadjuvant and adjuvant settings?
- How to approach the challenge of addressing metastatic disease with I-O?
- What next for patients who acquire resistance to I-O drugs?
What is needed at the strategic and practical levels to enable AI and machine learning to fully permeate the I-O space?
- Allowing the integration of disparate data sets for efficient clinical development
How to anticipate and alleviate the ongoing/future impact of COVID-19 pandemic-related disruption on immuno-oncology therapeutic clinical development?
Where is clinical trial design innovation required by the immuno-oncology space?
- Addressing the growing issue of underpowered early-phase trials
- Harnessing the potential of adaptive trial designs for the I-O field
- How to approach the challenge of predicting and planning for future standards of care when you are in early development?
Evolving approaches to the intensifying I-O patient recruitment challenge (particularly for biomarker-heavy studies)

Novel target and pathways: driving new approaches to tackling the TME and resistance to I-O therapeutics

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Novel target and pathways: driving new approaches to tackling the TME and resistance to I-O therapeutics

What are the key enabling technologies enhancing novel target identification and validation for antibody therapeutics and cellular immunotherapies? Exploring their capabilities and considerations for practical application
What tools can assist in targeting tumor-associated antigens? (Eg. MHC, peptide recognition)
Evaluating cellular immunotherapies (CAR T, TCR, NK, etc.) and bimultispecific antibody therapies in solid tumor indications
- Optimal approaches to improve specificity (eg. enhancing bispecific antibody avidity)
- Which novel targets and pathways are showing promise in improving response rates, efficacy?
  - Understanding mechanisms of resistance (eg. to CAR T cell therapy in melanoma)
  - Targeting multiple antigens
  - What are the next steps towards personalizing immuno-oncology therapy to the individual TME?
What progress with approaches to break up the tumor stroma, thus enabling penetration of TILs and other therapeutics?

Combination therapy development: strategic directions towards improving current I-O response rates

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Combination therapy development: strategic directions towards improving current I-O response rates

What key learnings can we take from the latest wave of checkpoint inhibitor combination trials?
- What are the chief considerations for combinations involving antibody drug conjugates? And what’s next for this particular field?
- Combinations with emerging checkpoint inhibitors – what is the data telling us?
- Combinations with TKIs/targeted therapies
How to further rationalize I-O combination therapy development?
- Regulator perspectives: evolving regulatory thinking on combination therapy selection and trial design
What unique insights into the TME are single cell RNAseq and spatial transcriptomic applications providing to help direct the design of combination regimens?

Safety: what progress in understanding and addressing immune-related adverse events?

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Safety: what progress in understanding and addressing immune-related adverse events?

How are the antibody therapeutic and cellular immunotherapy fields alike addressing the challenges of:
- Suppressing irAEs (eg. CRS, neurotoxicity)?
- Addressing on-target/off-tumor toxicity?
Assessing the role of the innate immune system in the development of irAEs
What platforms are demonstrating potential to aid in the prediction of toxicity?
How to optimally manage cancer patients with past irAEs and/or autoimmune diseases?

How to move towards precision I-O? Innovation in biomarker R&D

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How to move towards precision I-O? Innovation in biomarker R&D

Assessing the current state of play and identifying next steps in terms of discovering and developing reliable markers of response in solid tumors
- What new directions in biomarker discovery can novel and emerging I-O agents open up for the field (eg. LAG-3, cellular immunotherapies)?
What do resistance markers tell us about how to harness the innate immune system moving forward?
Exploring the cutting edge in imaging tools and their application in I-O (eg. PET-based tracer studies to monitor immune response; leveraging early imaging predictors to gain an idea of response; delivering noninvasive markers of disease)
What are the next steps for the field in capitalizing on the potential of single cell sequencing and analysis tools?
- Mass cytometry for simultaneous multiple marker analysis
  - Harnessing CyTOF (cytometry by time of flight) in combination with spatial imaging
Applying AI and machine learning to integrate biomarker data (eg. with longitudinal patient data) – what is practical both now and in the future?
Evaluating the potential of circulating plasma exosomes
What is the latest thinking in terms of the role of the microbiome and its impact on immune response?
Who will fund and drive the high-risk/high-reward novel biomarker research required by the I-O field moving forward?

Nonclinical tools update: are they improving in their capabilities of predicting clinical responses?

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Nonclinical tools update: are they improving in their capabilities of predicting clinical responses?

Emerging animal models. (How to better humanize immune-compromised mice? Utilizing bespoke CRISPR-derived ‘gene of interest’ mice)
Developing and validating appropriate cell models and organoids
What can resected tumors tell us about what changes in the TME following I-O dosing?
How to harness preclinical predictivity for co-stimulatory molecules?
Why aren’t preclinical models of antigen-specific T cells predictive of clinical success?
How and where is the combination of preclinical and clinico-genomic data helping predict patient response?
What are the keys to further accelerating speed to IND in the I-O space?
Regulatory perspective: how to approach nonclinical toxicology studies for personalized I-O therapeutics given the lack of good animal models available?
How to address cost and capability issues (of current DNA synthesis platforms, for example) to ensure continued advancement of synthetic biology in the I-O space?
How should we reconsider or redesign our R&D approach from discovery onwards if we are targeting second- or third-line treatment with I-O agents from the get-go?

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Leveraging the cutting-edge TME toolkit

What is the current extent of our understanding of the ‘how’ and ‘why’ of hot and cold tumors?
- Promising pathways to addressing the issue of T cell exhaustion
- What are the relevant dendritic cells in human tumors?
How and where is the application of key enabling technologies unlocking the secrets of the TME and tumor resistance to advance the immunooncology field?
- Multiomics approaches (genomics, proteomics, transcriptomics)
- Single cell analysis
  - Single cell RNA analysis (eg. of TILs)
- Non-invasive spatial imaging
  - What can high parameter cytometry (flow and mass) tell us about cell-to-cell interactions in the TME?
- Recent progress in understanding and measuring metabolism in situ in the TME (eg. measuring pH as a sign of immunoregulation)
How to better utilize these tools to gain further insights into I-O mechanisms of action? (Eg. why do checkpoint inhibitors work?)
How to address key data integration issues in deriving insights from novel analytical tools, particularly in terms of integration with disparate preclinical and clinical datasets?

Combination therapy development: emerging I-O therapeutic modalities and predictive technologies

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Combination therapy development: emerging I-O therapeutic modalities and predictive technologies

How and where are next-gen sequencing and analytical tools being effectively applied to improve predictability of safety and efficacy in the combination setting?
Reviewing combination therapy considerations and challenges, and defining next steps, for:
- Bi/trispecific antibodies
  - How to alleviate heightened toxicity risk for T cell redirection agents in combination?
- Cellular immunotherapies
  - Which tools are delivering insights into optimal combinations for CAR T cell and other cellular immunotherapies?
  - What are optimal pre-conditioning regimens in the solid tumor setting?
  - Exploring the logic of combining innate and adaptive immune system approaches
Oncolytic virotherapies
What can the latest clinical outcomes from regimens combining anti-PD-1 antibodies with intra-lesional therapies (TLR, STING, oncolytic viruses) tell us about their ability to impact distant disease sites?

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Immuno-oncology: tools of tomorrow 2023

Immuno-Oncology Insights’ annual exploration of enabling tools and therapeutic technology platforms likely to make a splash in 2023