Pre-Conference Focus Day

Targeted Protein Degradation for Anti-Infective Drug Development

In light of Covid-19, and with neglected and resistant diseases still being a huge untapped focus in 2022, it is now time to unite the industry experts in anti-Infectives to benchmark practices to utilize TPD for Anti-Infective Drug Development. This focus day is dedicated to understanding challenges & progress in the space of TPD anti-infective drug discovery & development, considering & translational learnings between all variants of anti-infectives towards novel non-oncology degrader drugs.

Tuesday 28th March

Evaluating Advancements Made in Drugging the Anti-Viral Space

9:30 am Chairs Opening Remarks

10:00 am Targeted Protein Degradation as an Antiviral Strategy

  • Priscilla Yang Professor, Department of Microbiology & Immunology, Stanford University School of Medicine

Synopsis

  • Conventional direct-acting antivirals inhibit or derange the activity of their viral targets with antiviral activity that is occupancy-driven
  • The event-driven pharmacology of antiviral degraders can be useful in increasing antiviral potency, raising barriers to resistance, and developing broad-spectrum activity

10:30 am Targeted Degradation of SARS-CoV-2 Proteases for Antiviral Therapy

  • Tauseef Butt President & Chief Executive Officer, Progenra

Synopsis

  • Targeted protein degradation of viral proteins has distinct advantages over the traditional drugs, chief being lack resistance.
  • SARS-CoV2 genome encodes two proteases, 3 CLpro (NSP3) and PLpro (NSP5), both are essential genes for the virus replication.
  • Progenra has developed PROTACs against SARS-CoV2 PLpro. The PLpro PROTACs are potent degraders of the protein and demonstrate superior antiviral properties as compared to parent PLpro inhibitors.
  • Mechanisms of the PLpro role in SARS-CoV2 propagation and PROTACs will be discussed

11:00 am Roundtable Learning Session: Learning the Difference Between Anti-Microbial, Anti-Viral, Anti-Fungal & Anti- Pathogenetic Drug Delivery to Gain Translational Learnings in ‘Undruggable’ Targets

Synopsis

Learning the Difference Between Anti-Microbial, Anti-Viral, Anti-Fungal & Anti- Pathogenetic Drug Delivery to Gain Translational Learnings in ‘Undruggable’ Targets

  • Discussing what are the common differences between all four anti-infective indications.
  • Focusing on what translational insights can be used to aid drug development across all targets.
  • Considering how we can unite future collaboration & knowledge sharing to propel the anti infectives field forwards.

12:00 pm Lunch Break & Networking

Looking at How to Successfully Drug the Anti-Microbial Space & Overcoming Resistance

1:30 pm Targeted Protein Degradation in Escherichia coli Using CLIPPERs

Synopsis

  • CLIPPERs are peptides that bridge the bacterial ClpXP protease to the Target
  • CLIPPERs cause degradation of endogenous target proteins in Escherichia coli
  • Degradation of essential target proteins by CLIPPERs has an antibacterial effect

2:00 pm Roundtable Learning Session: Evaluating a Combination of Therapeutic Approaches with TPD to Treat Anti-Microbial Resistance & Improve Patient Outcomes

  • Tauseef Butt President & Chief Executive Officer, Progenra

Synopsis

  • Understanding the different combination approaches currently available for resistant diseases.
  • Learning how combination approaches can combat challenges faced in mono-therapeutic approaches.
  • Theorizing how the field can utilize combination approaches in overcoming resistance.

3:00 pm Bacterial PROTACS: the Time is Now

  • Thomas Dick Center for Discovery and Innovation, Hackensack Meridian School of Medicine and Georgetown University

Synopsis

  • BacPROTACs demonstrate that linking a target to the bacterial caseinolytic protease enables degradation and, thus provide a strategy how the absence of E3 ligase – proteasome in bacteria can be overcome
  • This provides a path forward for the generation of antibacterial PROTACS targeting any protein of interest by employing the uncovered ‘proximity’ concept
  • Antibacterial PROTACs will not only expand the target space but may also improve efficacy by being more bactericidal and active against drug tolerant persister bacteria

3:30 pm BacPROTAC-induced degradation of ClpC1 as a new strategy against drug-resistant mycobacteria

  • Lukas Junk Postdoctoral Researcher, Helmholtz-Institute for Pharmaceutical Research Saarland

Synopsis

  • Hijacking the mycobacterial protease ClpC1:ClpP1P2 offers unique opportunities to overcome antimicrobial resistance
  • Outlining the development of natural product-inspired degraders, “BacPROTACs” that bind to the substrate receptor of the ClpC1:ClpP1P2 protease, priming neo-substrates for degradation.
  • Reviewing the degradation and anti-mycobacterial properties of homo- BacPROTACs that induce the degradation of ClpC1 in Mycobacterium tuberculosis

4:00 pm End of Pre-Conference Focus Day