8:30 am Check in & Coffee
9:25 am Chair’s Opening Remarks
Understanding the Why Behind Cytokine Failures & Looking Ahead to the Future to Maximize Cytokine Therapy Success
9:30 am Analysing Positive Global Trends in Specificity, Toxicity, & Clinical Success to Identify Promising Areas of Research
Synopsis
- Exploring the new and emerging strategies based on clinical failures and successes globally
- Reviewing the top disease indications reported with the most trial efficacy data presented to build from learnings
- Recognizing trends from investors within the cytokine space to gain a greater understanding of what they are looking for within Oncology and Immunology and Inflammation
10:00 am Morning Break
10:30 am Roundtable Discussion: Discussing Regulatory Strategy indications for Dose Optimisation & Expansion with Cytokine-based Drugs
Synopsis
- Overview of the history and evolution of Project Optimus and its application to understand how to manoeuvre in the regulatory environment when developing cytokines with an FDA perspective when approaching FDA optimization
- Discussing the pros and cons of Project Optimus to advance the regulatory development plan
- Interactive discussion with the attendees about their experiences in the regulatory landscape to successfully navigate regulatory issues
Understanding Toxicity Challenges & Improving Safety Profiles to Widen the Therapeutic Window
11:15 am Managing Toxicity Caused by The Over Expression of Cytokines to Widen the Therapeutic Window
Synopsis
Exploring the story behind the introduction of receptor bias to reduce toxicity and improve efficacy
Discussing the key strategies for optimizing cytokine potency while mitigating their inherent toxicity while considering the role of the therapeutic index in determining the clinical efficacy and safety of cytokine-based therapies
Examining whether toxicity is the primary limiting factor in achieving therapeutic benefit
and considering alternative factors that may influence the ‘therapeutic window’
11:45 am Manipulating the Immune System to Deliver Cytokines to Specific Cells
Synopsis
- Modulating cytokine affinity to bias towards preferential binding of the antibody over the cytokine
- Examining in vitro and in vivo models to characterize immunocytokine targeting and function
- Applying the same concept of targeting pd-1 delivery in T cells for Oncology indications and using this approach to deliver cytokines to supress immune responses rather than targeting tissues
12:15 pm Pulsed Cytokine Delivery for Anti-Tumor Immunotherapy & its Impact on Toxicity & Efficacy
Synopsis
- Investigating how we can better control the duration and intensity of cytokine signalling to improve therapeutic outcomes
- Exploring the use of intact, killed, non-pathogenic (Decoy) bacteria as a novel approach to induce pulsed cytokine release and anti-tumor activity in pre-clinical models
- Presenting data from a clinical oncology trial demonstrating pulsed and exceptionally broad cytokine induction, designed to improve safety and efficacy
12:45 pm Controlling the Achillies Heel of all T Cell Directed Therapies; Suppression of IL-2 Mediated Cytokine Release Syndrome by Combination with IL-10
Synopsis
- Discussing the therapies designed to enhance anti-tumor T cell efficacy and how they all share a common liability, the unpredictable induction of cytokine release syndrome (CRS) that is dissociated from efficacy
- Investigating how, independent of the mode of stimulation, activation of T cells results in secretion of IL-2
- Exploring IL-2 receptor binding leads to the induction of IFNg, TNFa, IL-6 and IL-1b, the hallmark proinflammatory cytokines of CRS. The combination of IL-2 with IL-10 protects the induction of IFNg, while suppressing the secretion of TNFa, IL-6 and IL-1b, thereby suppressing IL-2 mediated CRS and reducing toxicity associated with all therapies that
- activate or employ T cells
1:15 pm Lunch Break & Networking
Exploring Masking Strategies Used to Maintain Cytokine Activity Whilst Limiting Toxicity
2:15 pm Exploring the Potential of Cytokine-based Therapies to Modulate the Immune Response Specifically Within the Tumor Microenvironment
Synopsis
- Discussing strategies for designing cytokines, while highlighting the importance of understanding the complex interplay between cytokines, immune cells, and tumor cells to optimize therapeutic outcomes
- Investigating the impact of masking and unmasking strategies on cytokine activity, pharmacokinetics, and pharmacodynamics, while exploring the use of tumor-specific enzymes, pH gradients, and other triggers to unmask cytokines at the tumor site
- Exploring the use of artificial intelligence to rationally design of therapeutics and the selection of cytokine targets
2:45 pm Improving the Therapeutic Index of IL-2 Therapy through Masking & Antibody Targeting
Synopsis
- Discussing masking as a strategy to reduce systemic IL-2 activity and toxicity
- Investigating how PD-1 targeting can reconstitute IL-2 activity on tumor-reactive T cells
- Exploring the potential for synergistic combination to enhance the efficacy of CD3 Bispecifics and CAR-T therapy
3:15 pm Afternoon Break & Poster Session
3:45 pm Managing the Potency of Cytokines with Masking Strategies to Improve Safety
Synopsis
- Exploring how we can mute the potency of cytokines by using masks with attenuators considering the appropriate degree of attenuation
- Delivering cytokines to target cells without the need to leave your mask while maintaining full activity
- Using different masks on an ‘on and off’ rate to control the cytokines binding and strength to improve specificity
4:15 pm Tumor-activated INDUKINE Molecules: Improving the Therapeutic Index of Proinflammatory Cytokines for Cancer Immunotherapy
Synopsis
Illustrating the concept, design and preclinical validation of tumor-activated IL-2 and IL-12 INDUKINE molecules
Demonstrating that a prodrug strategy permits systemic dosing of wild type cytokines at exposures required for monotherapy activity
Integrating clinical safety, efficacy, PK and tumor biomarker data to establish POC for novel cytokine engineering strategies in FIH studies