8:00 am Coffee & Registration

9:00 am Chair’s Opening Remarks

  • Zac Cooper Director, Translational Medicine Lead, Astrazeneca

Investigating Adenosine Signaling in the Context of the Hypoxic Tumor Microenvironment

9:10 am The Discovery of Biochemical & Immunological Mechanisms of the Hypoxia- A2-Adenosinergic Immunosuppression as the Foundation of the Conceptually Novel Immunotherapies of Cancer Using Several Classes of Anti-Hypoxia-A2- Adenosingergic Drugs

Synopsis

• Highlighting that extracellular adenosine-A2AR/A2BR adenosine receptors-cyclic AMP-PKA axis: provides the “OFF” signal to TCR activated T-Cells and inhibit NK cells and other immune cells, triggers the immunosuppressive transcription of all other known immunosuppressive molecules like PD1 via cAMP Response Element (CRE) and CREB transcription factor

• Discussing that i) inhibition of adenosine-generating enzymes like CD39/CD73 or ii) degrading the extracellular adenosine with adenosine deaminase (ADA) or iii) blockade of A2AR A2B adenosine receptors can promote antitumor immunity

• Understanding how the Hypoxia-HIF-1alpha axis triggers the upregulation of the extracellular adenosine-generating enzymes and is upstream of Adenosine-A2AR/A2BR extracellular receptors to inhibit the anti-tumor immunity

• Exploring that weakening of the Hypoxia in tumors by systemic oxygenation or by oxygenation agents and inhibition of HIF-1alpha by inhibitors will also weaken the immunosuppressive signaling by adenosine-A2AR/A2BR axis downstream and thereby can promote antitumor immunity

• Understanding that even the refractory to all current immunotherapies tumors is expected to be rejected if the blockade of immunological negative regulators (like PD1/CTLA) is combined with anti-Hypoxia-A2-Adenosinergic drugs

9:40 am Regulation of the Adenosinergic Pathway in the Tumor Microenvironment & In Response to Therapies

  • Arabella Young Assistant Professor in the Department of Pathology; Investigator at the Huntsman Cancer Institute, The University of Utah

Synopsis

  •  Discussing the interaction between adenosine signalling in the tumor and with immune cells, particularly T cells and NK cells
  • Exploring regulation of adenosine in response to different stages of disease, or therapeutic modalities

10:10 am Anti-hypoxia Treatments to Reprogram The Tumor Microenvironment & Improve Cancer Immunotherapies

Synopsis

• Addressing the acute need in strategies to target the most upstream stage of the hypoxia- A2-adenosinergic pathway of immunosuppression in the tumor microenvironment (TME)

• Emphasizing reprogramming the TME by eliminating tumor hypoxia to improve outcomes of current cancer immunotherapies

10:40 am Speed Networking

Synopsis

This session is the ideal opportunity to get face-to-face time with many of the brightest minds working in the Adenosine field and establish meaningful business relationships to pursue for the rest of the conference.

11:40 am Panel Discussion – Which Cancers Are Addicted to Adenosine?

Synopsis

• Which types of cancer are going to respond to adenosine-pathway targeted therapy?

• Does the tumor microenvironment and measuring adenosine differ for each type of cancer?

• Will targeting a certain point in the pathway be more effective for certain cancers?

Leveraging Biomarkers to Evaluate Disease, Identify Patient Responders & Monitor Treatment for Adenosine-Pathway Targeted Cancer Immunotherapy

12:10 pm Can Biomarkers Be Used to Identify Patients Who Are Most Likely to Benefit from Adenosine-Pathway Targeted Cancer Immunotherapy?

Synopsis

• Discussing the role of adenosine in the tumor microenvironment

• Divulging biomarkers as surrogates for the presence of adenosine

• Highlighting the A2AR as a biomarker for response to inupadenant in iTeos clinical trials

12:40 pm Lunch Break

Assessing the Optimum Target in the Adenosine-Pathway

1:40 pm Chair’s Remarks

  • Xavier Leroy Chief Scientific Officer, Domain Therapeutics

1:45 pm Targeting CD39 in Malignancy: Immunotherapy & Inhibition of Angiogenesis

  • Simon Robson Professor of Medicine & Anesthesiology, Harvard Medical School, Scientific Founder Purinomia

Synopsis

• Explaining the central role of CD39 in modulation of purinergic signalling viz. regulation of both extracellular nucleotide pro-inflammatory and nucleoside/adenosine immunosuppressive pathways

• Demonstrating CD39 as a major rate limiting enzyme for extracellular nucleotide scavenging as well as adenosine production; given regulated catalysis of ATP/ADP to AMP and impacts of e.g. ADP on feed-forward inhibition on CD73

• Exploring the major strengths and possible limitations of targeting CD39 in the immune system and vasculature

• Highlighting the development of the therapeutic possibilities involved in the targeting of CD39

• Discussing how and where CD39 has been successfully targeted, providing ground work for understanding pathobiology/preclinical models/early clinical studies

2:15 pm Combining CD39 & CD73 Inhibition for Treatment of Pancreatic Cancer

Synopsis

• Discussing non-redundant functions of CD39 and CD73 in PDAC

• Presenting data to reveal novel mechanisms-of-action

2:45 pm Afternoon Break

3:45 pm Dual Targeting of CD73 & A2AR for Effective Suppression of Adenosine Signaling

  • Susanta Samajdar Senior Vice President and Head of Discovery, Aurigene Discovery Technologies Limited

Synopsis

• Exploring how inhibitions of either adenosine generation or signaling by inhibiting CD73 or A2AR have been shown to be effective therapeutic approaches

• Analyzing why the co-blockade of CD73 and A2AR results in a more pronounced antitumor activity than blockade of either likely due to increased CD73 expression upon A2AR inhibition and compensatory activity of other adenosine receptors

• Developing small molecule inhibitors that dually target CD73 and A2AR for use in combination with approved immunotherapeutic agents

4:15 pm Using a Novel Reporter Mouse to Investigate A2AR Expression Within the Tumor Microenvironment

  • Paul Beavis Associate Professor, Peter MacCallum Cancer Center

Synopsis

• Generating a reporter mouse that robustly exhibits GFP expression in A2AR positive cells

• Assessing how this reporter mouse allows interrogation of the cellular types and spatial location of cells expressing the A2AR within the tumor microenvironment

4:45 pm Interactive Roundtable Discussions

Synopsis

This session facilitates in-depth discussions among participants in an informal environment. After splitting into groups, participants will discuss key challenges and opportunities around their chosen topic:

  • Combination of Therapy
  • Investigating Drug Delivery Approaches for Appropriate Adenosine-PathwayTargeting

5:15 pm Chair’s Closing Remarks

  • Xavier Leroy Chief Scientific Officer, Domain Therapeutics