8:25 am Chair’s Opening Remarks

Defining HFpEF to Understand the Current Overall Diagnostic Approach

8:30 am Development of TN-301 – A Highly Selective HDAC6 Inhibitor for HFpEF Treatment

  • Tim Hoey Chief Scientific Officer, Tenaya Therapeutics

Synopsis

• Explore the discovery of HDAC6 as a novel target for heart failure through a high content screening approach in iPS-derived
cardiomyocytes
• Hear how TN-301 has activity in in vivo HFpEF models and works through multiple mechanisms of action including blocking fibrosis, inflammation, and modulating metabolic pathways
• Learn about IND-enabling studies that are being carried out for TN-301 and are advancing this compound to clinical development for the
treatment of HFpEF

9:00 am Myeloperoxidase – A Key Target Involved in the Progression of HFpEF

  • Regina Danielson Senior Vice President & Head of Research & Early Development, AstraZeneca

Synopsis

  • Learn how disease drivers in HFpEF are different to HFrEF
  • Understand how MPO is linked to HFpEF severity, and involved in fibrosis, inflammation, and microvascular dysfunction
  • Explore how inhibiting MPO has beneficial effects in patients with HFpEF

9:30 am Therapeutics in Heart Failure: Is HFpEF Really the Target?

Synopsis

  • Status report on therapeutics in HFpEF: comparison with HFrEF and lessons from SGLT2i’s
  • Stratifying patients with HFpEF: Which phenotype? Which disease?
  • Targeting the treatment population with consideration of metabolic CV disease.
  • Implications for clinical trial design.

10:00 am Moderated Discussion – Understanding HFpEF

  • Regina Danielson Senior Vice President & Head of Research & Early Development, AstraZeneca

Synopsis

  • Are we able to define the HFpEF patient?
  • Is HFpEF heterogeneous or is our understanding incomplete?
  • Is there a unifying hypothesis?

10:30 am Structured Networking

Synopsis

Have in-person 1-to-1 business introductions with other leaders and decision-makers prioritizing HFpEF drug development

11:00 am Morning Break

Targeting Translational Challenges Between Pre-Clinical & Clinical Trial Designs to Improve the Probability of Success

11:20 am Establishing a Consistent Framework & Endpoints to Optimize Clinical Trial Design

Synopsis

  • Evaluate whether new therapeutics should be included or be tested side
    by side to approved inhibitors
  • Improve the predictability of endpoints from Phase I to Phase II, and Phase II to Phase III clinical trials
  • Map out the most promising surrogate endpoints and biomarkers that
    allow for earlier identification of drug efficacy

11:50 am Human Ex-Vivo Drug Discovery in HFpEF Donor Hearts

Synopsis

  • Learn about procurement of hearts
  • Explore RNA transcriptomics analysis
  • Discuss response to drugs
  • Asses a next-generation HFpEF model

12:00 pm Understanding the Promise & Pitfalls of Pre-Clinical Models of HFpEF for a More Accurate Representation of the Human Disease

Synopsis

  • Overview an up-to-date summary of HFpEF models and comparisons to patient phenotypes
  • Review the clinical translation of old and new heart failure therapies
  • Discuss exciting novel disease mechanisms derived from HFpEF models
  • Analyze a realistic appraisal of HFpEF models purpose and value plus
    suggested future research directions

12:30 pm Novel Animal Models of HFpEF with Metabolic Comorbidities for Translational Drug Efficacy Studies

Synopsis

  • Discuss the limitations of high fat diet-induced obese mouse and rat models for HFpEF
  • Describe the Spontaneously Diabetic Torii (SDT) fatty rat and the LundMetS rat models to target HFpEF in the context of diabetic nephropathy and NASH
  • Present the free-choice diet-induced obese NASH hamster, a preclinical model with severe diastolic dysfunction and restrictive profile

12:40 pm Assessing the Current & Future Landscapes for Preclinical Models

Synopsis

  • Dissecting the advantages and disadvantages of current established preclinical models
  • Ascertaining what should be done to improve translatability of animal models without extending drug development timeline
  • Expanding our understanding of mechanisms driving safety for HFpEF targeted candidates

1:00 pm Networking Lunch

Expanding Current Methods Used to Identify pEF Patients for Faster Diagnosis & Treatment

1:45 pm Disease Drivers in HFpEF – With Focus on Microvascular Inflammation

  • Regina Danielson Senior Vice President & Head of Research & Early Development, AstraZeneca

Synopsis

  • Examine clinical evidence of microvascular inflammation in HFpEF
  • Assessing molecular signatures of microvascular dysfunction in HFpEF
  • Gain insights into clinical diagnosis of microvascular dysfunction in HFpEF

2:15 pm Use of Cardiac Imaging in HFpEF Clinical Trials: Should it be Part of Enrollment Criteria or Trial End Points?

  • Sheldon Litwin Board-certified in general cardiology, Medical University South Carolina

Synopsis

  • Understand how cardiac imaging may provide supporting evidence for the diagnosis of HFpEF, eventhough the sensitivity and specificity of cardiac imaging for establishing this diagnosis are still uncertain
  • Assess how imaging has the potential to be very useful in identifying subtypes of HFpEF (phenotypes or phenogroups) and thus, allow a more targeted or personalized treatment approach
  • Learn how changes in cardiac structure or function identified by certain imaging tests may be appropriate endpoints for clinical trials, and may be easier to use than clinical endpoints

2:45 pm PRO-C6 as a Patient Enrichment Tool for HFpEF Clinical Trials

Synopsis

  • Explore biomarkers to identify different endotypes of HFpEF patients are highly needed for precision medicine
  • Discuss how collagen type VI and its signaling – molecule endotrophin have received attention in several pathological processes
  • Analyze PRO-C6, a biomarker of collagen type VI formation and endotrophin, is a powerful prognostic biomarker in HFpEF
  • Learn how PRO-C6 has received a letter of support from the FDA as enrichment tool in HFpEF

 

3:00 pm Utilizing Cell-Based Therapies for HFpEF by Focusing on Animal Models

Synopsis

  • Standardizing differences between commonly used techniques in animal models
  • Highlighting the importance of exercise measurements in the context of proof-of-concept trials
  • Proving the importance of measuring the pressure in comparison to
    inferring it

3:30 pm Panel Discussion – Could Imaging be Taken Further? Thinking Unconventionally About Diagnosis

  • Sheldon Litwin Board-certified in general cardiology, Medical University South Carolina
  • Sunjay Kaushal Founder & Chief Medical Officer, NeoProgen Inc.
  • Regina Danielson Senior Vice President & Head of Research & Early Development, AstraZeneca
  • Federica Genovese Director of Renal & Cardiovascular Research , Nordic Bioscience

4:00 pm Afternoon Break & Networking

Examining the Role of Genetic Predisposition in HFpEF

4:30 pm Considerations in Utilizing Oligonucleotide-Based Therapeutics to Prevent or Treat HFpEF

  • Sean Bedingfield Research Engineer – Drug Delivery, Eli Lilly Company – New Therapeutic Modalities

Synopsis

  • What are the circumstances and performance criteria to justify oligonucleotide use when small molecule inhibitors are clinically available?
  • Assess antisense oligonucleotides, small interfering RNA, and prevalent delivery strategies with their respective strengths and weaknesses
  • Hear best case practices in experimental evaluation of renal and endocrine oligonucleotide therapies

5:00 pm Increased Lipoprotein Metabolism & HFpEF – A Double-Edged Sword?

Synopsis

  • Evaluate data on how genetic alerting the balance of lipids and lipoprotein uptake affects lipids accumulation in cardiomyocytes
  • Discover the effects of favouring cardiac lipotoxicity and HFpEF in vivo in
    experimental models

5:30 pm Moderated Discussion – Consideration of Gene Therapy Effectiveness Resulting from Insights into Genetic Predisposition

6:00 pm Scientific Poster Session

Synopsis

  • Connect with your peers in a relaxed
  • atmosphere and continue to forge new and exciting relationships.
  • Share your research or learn from your peers sharing their exciting work
    and latest findings

7:00 pm End of Day One