Virtual poster discussion session 2

26 January 2022

  • days
  • Hours
  • Minutes

Chair and moderators

Peter Dorfmüller, Justus-Liebig University Giessen, Germany

Max Gassmann, University of Zurich, Switzerland

Mark Geraci, University of Pittsburgh, USA

Victor Tapson, Cedars-Sinai Medical Center California, USA

Joan-Albert Barbera, Hospital Clinic de Barcelona, Spain

Bradley Maron, Brigham and Women's Hospital, Harvard Medical School, USA

Agenda

  • Jair Tenorio // Novel TRAF2 variant and KDR deletion are implicated in the pathogenesis of pulmonary arterial hypertension
  • Andrea Frump // Loss of Estrogen Receptor Alpha (ERα) Worsens Hemodynamic Alterations and Right Ventricular (RV) Adaptation in Female Rats with Pulmonary Hypertension (PH)
  • Victoria Toro // Breast cancer and heritable PAH due to BMPR2 mutation: an unexpected discovery
  • Steven Yuanjun Shen // Smooth Muscle Tsc2 deficiency leads to spontaneous pulmonary hypertension and represents attractive molecular target for therapeutic intervention 
  • Chanil Valasarajan // Identification of ADORA1-PDE10A Complex Formation and Its Bidirectional Regulation of Intracellular Cyclic AMP Levels as a Novel Therapeutic
  • Tessa Wilke // Downregulation of adenylate kinase 4 (AK4) improves the mitochondrial respiration and inhibits the glycolytic switch of pulmonary arterial smooth muscle cells
  • Thomas Lacoste Palasset // Association between Leflunomide and Pulmonary Hypertension
  • Youlan Rao // The Estimand Framework in PAH Clinical Trials
  • Athiththan Yogeswaran // Risk stratification in pulmonary hypertension due to chronic obstructive pulmonary disease
  • Dheyaa Alkhanfar // Small pulmonary vessels in severe pulmonary hypertension associated with chronic lung disease
  • Jack Li // A Phase 1, open-label, crossover study of inhaled seralutinib to assess potential effects on the pharmacokinetics (PK) of cytochrome P450 (CYP) and transporter substrates in healthy subjects
  • Faisal Alandejani // Cardiac MRI and risk stratification in pulmonary arterial hypertension: evaluation of ESC/ERS thresholds for right atrial area

A deeper look

Round 1: BASIC

Novel TRAF2 variant and KDR deletion are implicated in the pathogenesis of pulmonary arterial hypertension

15:00-15:05 GMT

Presenter: // Jair Tenorio, La Paz University Hospital, Spain

Best abstract

 

Loss of Estrogen Receptor Alpha (ERα) Worsens Hemodynamic Alterations and Right Ventricular (RV) Adaptation in Female Rats with Pulmonary Hypertension (PH)

15:20-15:25 GMT

Presenter: // Andrea Frump, Indiana University School of Medicine, USA

Awaiting further information

 

Breast cancer and heritable PAH due to BMPR2 mutation: an unexpected discovery

15:30-15:35 GMT

Presenter: // Victoria Toro, Quebec University Institute of Cardiology and Pneumology, Canada

Best abstract

 

Smooth Muscle Tsc2 deficiency leads to spontaneous pulmonary hypertension and represents attractive molecular target for therapeutic intervention

15:40-15:45 GMT

Presenter: // Steven Yuanjun Shen, School of Medicine, University of California, Davis, USA

Heterozygous deletion of Tsc2 in vascular smooth muscle cells leads to spontaneous pulmonary hypertension in mice. Pharmacological restoration of Tsc2 by Sirt1 activator SRT2104 reverses pulmonary vascular remodeling, decreases percentage of occluded pulmonary arteries, and resolves SU5416-hypoxia-induced severe pulmonary hypertension in rats.

 

Identification of ADORA1-PDE10A Complex Formation and Its Bidirectional Regulation of Intracellular Cyclic AMP Levels as a Novel Therapeutic

15:50-15:55 GMT

Presenter: // Chanil Valasarajan, Max-Planck-Institute for Heart and Lung Research, Germany

Best abstract

 

Downregulation of adenylate kinase 4 (AK4) improves the mitochondrial respiration and inhibits the glycolytic switch of pulmonary arterial smooth muscle cells

16:00-16:05 GMT

Presenter: // Tessa Wilke, Justus-Liebig University Giessen, Germany

The role of Adenylate kinase 4 (AK4) in Pulmonary Hypertension is mostly unknown. Studies have shown that AK4 is a key player in hypoxia mechanisms of lung cancer. Our aim was to identify the effect of AK4 under hypoxia in PASMCs in humans and to find further pathways of metabolic reprograming linking it to the existing knowledge of Pulmonary Hypertension.

 

Round 2: CLINICAL

Association between Leflunomide and Pulmonary Hypertension

16:10-16:15 GMT

Presenter: // Thomas Lacoste Palasset, Paris-Saclay University, France

Best abstract

 

The Estimand Framework in PAH Clinical Trials

16:20-16:25 GMT

Presenter: // Youlan Rao, United Therapeutics Corp, USA

A statistical concept of estimand was introduced in the newly published ICH E9 addendum. The addendum introduced this concept  to ensure alignment of the objectives of a clinical trial with its design, conduct, and analysis.

With the endorsement of ICH E9 addendum by regulatory bodies, the word estimand will become a staple of medical jargon in the future when discussing clinical trials.

In this talk, we discuss how the estimand framework and the five estimand attributes may be applied to the common designs in pulmonary arterial hypertension clinical trials. The common intercurrent events in PAH studies and the strategies to handle them will also be discussed.

 

Risk stratification in pulmonary hypertension due to chronic obstructive pulmonary disease

16:30-16:35 GMT

Presenter: // Athiththan Yogeswaran, Justus-Liebig-University Giessen, Germany

Awaiting further information

 

Small pulmonary vessels in severe pulmonary hypertension associated with chronic lung disease

16:40-16:45 GMT

Presenter: // Dheyaa Alkhanfar, University of Sheffield, UK

Best abstract

 

A Phase 1, open-label, crossover study of inhaled seralutinib to assess potential effects on the pharmacokinetics (PK) of cytochrome P450 (CYP) and transporter substrates in healthy subjects

16:50-16:55 GMt

Presenter: // Jack Li, Gossamer Bio, Inc., San Diego, USA

Seralutinib, a highly potent, small molecule kinase inhibitor that targets PDGFRα/β, CSF1R, and c-KIT, and modulates BMPR2, is being developed as a treatment for pulmonary arterial hypertension (PAH). The direct pulmonary delivery of seralutinib via dry powder inhalation is expected to potentially maximize its therapeutic index by directly targeting diseased pulmonary arterioles, minimizing systemic exposure, and decreasing the potential for off-target adverse effects.

Based on in vitro predictions and the fact that patients with PAH commonly receive multi-drug therapeutic regimens to control the disease, this study evaluated potential effects of inhaled seralutinib on the pharmacokinetics of a cocktail of CYP enzyme and transporter substrates in healthy subjects. These drug-drug interaction assessments may inform approaches to evaluating seralutinib-based combinations in the clinical development program, including the currently enrolling phase 2 TORREY study.

 

Cardiac MRI and risk stratification in pulmonary arterial hypertension: evaluation of ESC/ERS thresholds for right atrial area

17:00-17:05 GMT

Presenter: // Faisal Alandejani, University of Sheffield, UK

Best abstract

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