8:50 am Chair’s Opening Remarks

9:00 am Epigenetics: A Gatekeeper for DNA Replication & ecDNA Amplification

  • Johnathan R. Whetstine, PhD Professor, Jack Schultz Basic Science Endowed Chair Director, Cancer Epigenetics Institute Program Co-leader Cancer Signaling and Epigenetics, Fox Chase Cancer Center

Synopsis

  • Demonstrate that epigenetic pathways control extrachromosomal DNA amplification
  • Demonstrate that epigenetic therapeutics are able to block or promote DNA amplification
  • Highlight roles for epigenetic factors in DNA replication and rereplication

Maximizing Efficacy Through Rational Drug Combinations

9:30 am Global Optimization of Combinatorial Drug Enable by AI-PRS Platform

Synopsis

  • In large scale combinatorial drug search and in personalized combinatorial therapy, N doses for each drug of a M drug combination form a huge NM search space. AI-PRS platform enables us to home in the optimized drug-dose combination with orders of magnitude saving in time and cost
  • In 1012 drug-dose combinations, the search of killer combos for inhibiting COVID-19 infection only takes two weeks
  • AI-PRS is an indication agnostic platform and have been demonstrated in more than 30 disease models including customized regimen for a specific patient. Clinical trials of personalized therapies for cancers, infectious diseases and organ transplants have been successfully accomplished

10:00 am Targeting Two Erasers: Dual Inhibition of HDACs and LSD1

  • A. Ganesan Professor , University of East Anglia

Synopsis

  •  Potent and selective inhibition of two epigenetic targets
  • Activity and dual target engagement in acute myeloid leukemia cells
  • Synergy with doxorubicin, enabling effective use of sublethal drug concentrations

10:30 am Morning Networking Break

Create Value by Taking Aim at Novel Indications

11:00 am CC-90011, a Potent, Oral, & Reversible LSD1 Inhibitor

Synopsis

  • CC-90011, a potent, oral, and reversible LSD1 inhibitor, has been shown to be very well tolerated in patients
  • With follow-up as long as 44 cycles of treatment, no new AEs were identified; most TEAEs were mild, reversible, and easily manageable by short dose interruptions and dose modifications
  • Review early evidence of antitumor activity that was observed with CC- 90011 in some NENs and NHLs
  • Discuss how these data support further investigation of CC-90011 as a promising therapy

11:30 pm Epi-drugs in Parasites

Synopsis

  • HDAC and DNMT inhibitors against malaria
  • SmHDAC8, SmSIRT2 and LSD1 inhibitors against S. mansoni
  • New SIRT inhibitors against T. cruzi

12:00 pm Transitioning from Haematological to Solid Tumors

  • Kai He Assistant Professor of Medicine, Ohio State University Comprehensive Cancer

Synopsis

  • Discuss how DNA Methyltransferase and Histone Deacteylase contribute to epigenetic mediated silencing of Tumor suppressor genes and how it could be possible to reverse this
  • Look retrospectively at the success in leukaemia and other
    haematological malignancies
  • Highlight the critical challenges obstructing the development of a drug for solid tumor disease
  • Discover future implications, plans and how epigenetics could be a part of precision medicine in solid tumor oncology

12:30 pm Lunch Networking Break

1:00 pm DUR-928, DNMTs and Alcohol-Associated Hepatitis

Synopsis

  • DUR-928 is an epigenetic regulator that inhibits DNMTs
  • Hypermethylation and elevated DNMTs are associated with alcohol-associated hepatitis
  • DUR-928 clinical results and ongoing program in alcohol-associated hepatitis

1:30 pm Phosphorylation of Histone H3.3 at Serine 31 Promotes p300 Activity

  • Laura Banaszynski Principal Investigator , University of Texas Southwestern Medical Center

Synopsis

  • H3.3-specific S31 phosphorylation stimulates activity of the acetyltransferase p300 in trans, suggesting that H3.3 acts as a nucleosomal cofactor for p300 at enhancers
  • Depletion of H3.3 from mESCs results in a substantial reduction of acetylation on histone H3 at lysine 27 (H3K27ac) at enhancers
  • Cells lacking H3.3 demonstrate reduced capacity to acetylate enhancers that are activated upon differentiation, along with reduced ability to reprogram cell fate

Discovering New Epigenetic Therapeutics

2:00 pm Discovery of Small Molecule Modulators of Epi Targets

2:30 pm Next Generation Drug Discovery at Fulcrum Therapeutics: FTX-6058, A Novel EED Inhibitor To Increase Fetal Hemoglobin Expression For the Treatment of Select Hemoglobinopathies

  • Drew Thompson Vice President - Molecular Innovation & Pharmaceutical Development, Fulcrum Therapeutics

Synopsis

• Fulcrum Therapeutics identifies drug candidates to treat rare genetic
diseases at their root cause
• FulcrumSeek as a next generation Product Engine for drug discovery
• Case Study 1: Discovery of FTX-6058, a novel EED inhibitor to increase
fetal hemoglobin for the treatment of select hemoglobinopathies

3:00 pm Afternoon Networking Break

3:30 pm Clinical Development of The BET Bromodomain Inhibitor ZEN- 3694 In Solid Tumors: Lessons Learned

  • Eric Campeau Senior Director of Translational Medicine , Zenith Epigenetics

Synopsis

-Design of epigenetic combinatorial therapies
-Clinical activity in breast and prostate cancer patients
-Mechanisms of action: similarities and differences between the prostate
and breast cancer trials

4:00 pm Designing Biomarkers That Enable Accurate Translation of Combination Therapies

  • Alon Goren Assistant Professor, University of California San Diego

Synopsis

  • Discussing how biomarkers can help investigators make decisions about correctly timing doses
  • Identifying and validating novel biomarkers

4:00 pm Wrap-up Roundtables

Synopsis

The Role of Epigenetics in a Wider Oncology Portfolio

  • Process the knowledge gained from the previous case studies and
    discussions in this interactive discussion
  • Get one last chance to make connections with people on parallel paths to yours