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Longevity Tech Fund Webinar - Series 1.0 - Spot light - Celeris Therapeutics - Summary

July 22, 2022

In the first LTF webinar of the series, Chris Trummer CEO of Celeris Therapeutics (https://celeristx.com/) spoke to us (Jyothi Devakumar and Naftali Horwitz) about the exciting advances at Celeris Therapeutics is making. Celeris develops the next generation of therapeutic modalities called PROTACs. Below we have provided a brief intro to the tech and also highlighted some of the salient takeaways from the webinar. 

As we all know, the human body is a cell collective held together by an extracellular matrix in a defined shape and form. Cells within themselves and in the cellular milieu are in a state of homeostasis which gets disrupted as aging sets in. This disruption extends to the structure, function and life of these proteins. All proteins are degraded by highly regulated machineries within the cell and when these mechanisms break down, diseases set in. A few well known diseases such as Parkinsons, Alzheimer's.

Companies such as Celeris are developing a class of molecules called PROTACs or PROteolysis Targeting Chimeras which function as molecular glues to bring together protein targets of interest and the components of the innate proteasomal degradation system. One end of the molecule interacts with proteins of interest that can be misfolded proteins or a protein that is present in excess or just a protein whose absence, either transiently or permanently benefits the health of the cell and in turn the health of the individual. The other end of the molecule binds a player in the protein degradation pathway, better known as an E3 ligase, enabling efficient degradation/turnover of the proteins.

Given how important and transformative the technology is and the human impact value especially to the evolving field of longevity, we had a lot of questions for Chris. This webinar turned out to be an exciting journey tracing the future of drug discovery.

Here are some of the excerpt from the discussion

  1. Chris Trummer and the team at Celeris have had lifelong interests in both biotechnology and data driven approaches. These interdisciplinary approaches influence the team’s ability to leverage data that naturally accumulates within the whole drug development process in order to come up with novel therapeutic modalities that might benefit human health.
  2. PROTACs are unique drug modalities that, due to the nature of their loose binding kinetics, may make a whole host of so-called “undruggable” targets, druggable. Alongside this, because PROTACs don't need to rely on occupancy driven pharmacology (which simply means having to physically bind to the active site of the protein) and because they target a protein for degradation instead of stable inhibition, these drugs can drive a completely different pharmacological response. As such, Celeris anticipates that these modalities will overtake more traditional drug modalities 
  3. Likewise, PROTACs do not conform to a single shape and size. In general humans have hundreds of E3 ligases (one of the mediators of protein degradation) currently known and Celeris can hijack almost all of them to make novel PROTACs. Some of these E3 ligases are even tissue specific which allows for more selectivity. On top of that, there are a whole variety of targeting chimaeras that are leveraging autophagy for instance as well as lysosomal targeting chimaeras. Celeris is agnostic as to how they achieve protein degradation whether the biology they co-opt is utilising the proteasome, autophagy or the lysosome ( different types of protein degradation mechanism that exist within the cells). 
  4. Given the extensive combinatorial nature of these PROTAC designs, Celeris heavily relies on artificial intelligence techniques like so-called geometric deep learning to accurately predict binding interfaces between proteins. 
  5. Celeris is interested in developing PROTACs for neurodegenerative diseases like Parkinsons and Alzheimer’s disease where protein adducts and misfolded proteins actively contribute towards pathology. Specifically, they are actively targeting alpha synuclein which is implicated in Parkinsons and other so-called synucleinopathies.
  6. The field has grown exponentially in the two years since Celeris was founded with an annual growth rate of ~40% or so. Currently there are PROTACs in clinical trials targeting androgen receptors which are central to the survival of both prostate and breast cancers. Celeris anticipates that this is just the tip of the iceberg and a large majority of drug targets will utilise PROTAC technologies. 
  7. This is a multi billion dollar industry with the potential to transform drug discovery
  8. It is worth noting that Celerix maximises operational and economic leverage via split presence and operations between Austria and the US. They have recently built a state of the art lab with the complete capability to conduct R&D needed to reach the goal post faster and cheaper.

Celeris is well poised to disrupt drug development and the pharmacologic industry as a whole. Alongside their internal pipeline, they have two active collaborations with Merck KGaA and Boehringer Ingelheim. They are in the midst of a Series A round aiming to raise $25M and expect to be able to reach IND-enabling studies in the next year. In the past two years Celeris has seen a considerable expansion in the amount of companies pursuing this type of drug modality and they expect that companies pursuing PROTACs will take a large chunk of the biotechnology market share. More importantly though, they expect that these drugs will have an enormous impact on patient lives as they open the door to target what has thus far been considered undruggable.