7:30 am Morning Check-in & Light Breakfast
8:15 am Chair’s Opening Remarks: Considerations on What Helps to Keep Biotech Companies Moving Forwards in Spite of Difficult Times
Addressing Failures Across Cytokine Based Drug Development to Examine the Evolving Industry & Highlight Exciting Novel Directions for the Field
8:30 am Exploring the Cytokine Therapeutics Landscape: Where Are We Now?
Synopsis
- Overview of the oncology and non-oncology cytokine-based drug development landscape, both preclinical and clinical
- Analyzing and evaluating companies exiting the field or dropping cytokine pipelines
- Outlining novel cytokine engineering strategies
9:00 am Engineered PD1-IL15 Improves Intratumoral CD8+ T cell Function and Antitumor Immunity
Synopsis
- Designing PD1-IL15 to deliver stimulation to PD1+ tumor-infiltrating lymphocytes (TIL) while minimally affecting circulating peripheral natural killer (NK) cells and T cells
- The PD1-IL15 mouse surrogate promotes CD8 T cell-dependent anti-tumor Immunity
- Enhancing efficacy compared to the combination of aPD1 with an IL-15 Superagonist
9:30 am A Brief History of the Cytokine Field: New Frontiers for Cytokine Based Drug Development
Synopsis
- Delving into previous experiences from cytokine therapeutic development across the years
- Identifying early approaches that had limited success
- Evaluating novel innovations driving more sophisticated cytokine development
10:00 am Speed Networking & Morning Break
Uncover Positive Clinical Updates & Hear Key Translational Learnings from the Journey to the Clinic
11:00 am Updating the Clinical Progress of DK210 (EGFR), Fusing IL-10 With wtIL-2 to Prevent Toxicity & Enhance Potency
Synopsis
- Treating patients with cold tumors has already elicited potent peripheral immune activation leading to confirmed stable disease of stage 4 PDAC, and unconfirmed stable disease of patients with stage 4 CRC
- Indicating DK210 (EGFR) has successfully blunted IL-2 inflammatory toxicity while retaining potent immunological activation and dramatically improved its therapeutic index
- Outlining how responses stimulated in a predictive in vitro assay correlate with patient anti-tumor responses on therapy, suggesting the capacity to select patients that are most likely to respond
11:30 am Pioneering Cytokines & Growth Factors: Transforming Research & Healthcare
Synopsis
- Outlining cytokine quality (purity, bioactivity, batch-to-batch consistency)
- Producing GMP-grade cytokines (regulatory documents and guidelines, products, applications)
- Exploring applications of our cytokines (cell culture, organoid culture diagnostic biomarkers, cytokine receptors as biomarkers)
11:40 am XTX501, a Tumor-Activated PD1/IL2 Bispecific Molecule, Designed to Stimulate & Expand Antigen-Experienced T cells in the Tumor Microenvironment
Synopsis
- Design of XTX501 and key components
- Rationale for targeting IL-2 to PD1-positive T cells and importance of masking
- Overview of preclinical data including PK and tolerability in non-human primates
12:10 pm Exploring how BPT567 (PD1-IL18) Induces Potent Anti-tumor Immune Responses
Synopsis
- Revealing BPT567 as an immunoconjugate (IC) consisting of an IL-18 binding protein-resistant IL-18 payload that is chemically conjugated to a PD-1-blocking antibody
- Triggering a profound expansion of intratumoral PD1+ CD8+ T effector memory cells accompanied by a high local induction of IFNg release within the tumor microenvironment.
- Outlining BPT567 exhibiting a strong anti-tumor efficacy at remarkably low doses of the IL-18 payload, which can be attributed to its ability to potently induce cis-signaling in PD-1+ T cells.
12:40 pm Lunch Break & Networking
Interrogating Our Understanding of Cytokine Mechanisms to Develop Targeted Cytokine-Based Therapeutics
1:40 pm Revealing Cytomask®: Cis-Demasking Cytokine Technology for Targeted Delivery
Synopsis
- Outlining masking cytokine technology, allowing activity on-demand at the Right Site but suffers from enzyme selectivity
- Cis-delivery cytokine technology allows redirection of activity on the right cells but requires potent cytokine attenuation and non-optimal cell selectivity
- Cytomask® is a novel Cis-Demasking cytokine technology avoiding cytokine attenuation and lack of selectivity of cleavable linkers to unmask cytokine specifically on immune cells expressing the appropriate target
2:10 pm Precision Engineering of Cytokine Therapeutics by Measuring Protein Interactions at Scale With AlphaSeq
Synopsis
- Utilizing AlphaSeq, a tool for massive PPI data generation, IFNA2 and IL-21 cytokine variants are engineered with varied affinities for human and mouse receptors, guiding precision development of cancer therapeutics with reduced systemic toxicity
- Exploring protein affinities and signaling potencies were orthogonally measured using biolayer interferometry and human PBMC phosflow assays, leading to the fusion of promising cytokines with anti-CD8 antibodies, significantly enhancing signaling potency in targeted cells
- Enabling the creation of a therapeutic matrix of cytokines and antibodies, enhancing specificity and efficacy in targeted cancer treatments in immuno-oncology
2:40 pm Blockade of Common Gamma Chain Cytokine Signaling With REGN7257, an Interleukin 2 Receptor Gamma (IL2RG) Monoclonal Antibody
Synopsis
- Blockade of cytokine signalling protected mice against immune cell-mediated pathology in multiple disease models
- Providing evidence of γc cytokines as key drivers of pathogenic immune cell responses
- Offering a potentially novel strategy for the management of inflammatory and autoimmune diseases, such as GVHD, immune aplastic anemia and MS
3:10 pm Afternoon Break & Networking
Engineering Your Molecule for Enhanced Specificity, Reduced Toxicity & a Widened Therapeutic Index
3:40 pm New Cytokine Targeting Strategies Enabled by Multivalent Cis-Targeted Complexes
Synopsis
- Introducing how tetravalent, cis-targeting cytokine-Fc fusions have unique selectivity advantages
- Outlining a computational model to coordinately engineer targeting alongside signal quality and potency
- Demonstrating that selectively delivering various cytokines enables optimization for specific immune functionalities
4:10 pm Harnessing mRNA-encoded Cytokines as Immune Therapeutics for a Focused Immune Response
Synopsis
- Engineered cytokines encoded by nucleoside modified mRNA and delivered in LNPs enables tailored and focused immune therapeutics
- Multiplexing a myriad of cytokines by the mRNA/LNP platform allows next-generation broad immunomodulation for clinical benefit
- Providing examples of harnessing mRNA technology for manipulating the immune response via cytokines for autoimmune and inflammatory disease
4:40 pm Design of Cytokine/antibody Fusion Proteins to Develop Novel Immunotherapeutics
Synopsis
- Linking interleukin-2 (IL-2) to an anti-IL-2 antibody modulates cytokine behavior for selective and effective disease targeting
- Cytokine pleiotropy allows for development of interventions against cancer, infection, and autoimmune diseases
- Structural insights guide engineering of cytokine/antibody fusion proteins to optimize assembly, stability, and therapeutic activity
5:10 pm Chair’s Closing Remarks
5:20 pm End of Conference Day One
No day selected