Overview
EpiBiologics, a one-year-old company, is making waves in targeted protein degradation. They aim to tackle membrane and extracellular proteins, which have been tough targets for drug developers. Ann Lee-Karlon, PhD, is leading the charge as CEO. With her experience at Genentech and Altos Labs, she joined EpiBiologics in July 2023. The focus is on moving protein degradation into the extracellular space, covering about 40% of the proteome.
The platform is centered on EpiTACs, a modular bispecific antibody-based system. Developed by renowned antibody engineer Jim Wells, PhD, of UCSF, EpiTACs target disease-driving extracellular and membrane proteins in a tissue-specific manner. One arm of the bispecific antibody targets the protein, while the other is tissue or disease-specific, enhancing the therapeutic index.
EpiBiologics hit the ground running in March 2023 with $50 million in Series A funding. This initial funding, led by Mubadala Capital and Polaris Partners, grew to over $70 million with contributions from Digitalis Ventures, Taiho Ventures, and Codon Capital. With this financial backing, the company is poised for rapid development.
Categories of Degraders
EpiBiologics has a broad catalog of over 270 degrader arms for their EpiTACs, divided into three main categories:
- AbTACs: Facilitate the interaction between the target protein and transmembrane E3 ligases. This enables ubiquitination and degradation of membrane proteins by the proteasome.
- KineTACs: Utilize the internalization mechanism of chemokine or cytokine receptors. They bind to the receptor through the native ligand, leading to lysosomal degradation of both soluble and membrane targets.
- TrainTACs: Use various internalizing receptors to transport membrane and soluble extracellular proteins for lysosomal degradation.
Tissue-Specific Degraders
EpiBiologics stands out due to their focus on tissue specificity. Other companies might have powerful degrader arms, but they often lack tissue-specific expression. EpiBiologics’ technology aims to address this by offering tissue-specific degraders that limit on-target toxicity and resistance mechanisms.
A prime example of this is their work on the epidermal growth factor receptor (EGFR). EGFR is a well-known cancer target with limitations due to on-target toxicity in the skin and resistance mechanisms. EpiBiologics’ degraders can limit this toxicity by targeting the tissue without affecting normal tissue. This also reduces the downstream signaling that EGFR can induce, something that simple blockade of EGFR can’t achieve.
Independent of EGFR Mutational Status
EpiTACs show activity independent of EGFR mutational status. This means they can target different mutational forms by driving degradation from the outside, regardless of the intracellular form. This characteristic broadens the range of targets that can be pursued, making EpiBiologics’ approach more versatile.
Broad Range of Targets
The technology is not limited to EGFR. EpiBiologics is also looking at ion channels and G-protein-coupled receptors (GPCRs), which are challenging to target with small molecules. Their team has built and tested over 1,000 EpiTACs, demonstrating the scalability and manufacturability of their platform.
Developmental Progress
EpiBiologics is making rapid progress. Their priority this year is to identify developmental candidates. The EpiTac platform’s speed allows for quick transitions from initial studies to in vivo proof-of-concept. This enables benchmarking against the standard of care and demonstrating survival benefits.
The goal is to nominate a candidate for an investigational new drug (IND) application by the end of the year. Lee-Karlon aims to select a development candidate and possibly have more than one ready. The team is ensuring all activities align to meet timelines appropriately, drawing from Lee-Karlon’s experience in leading drug approvals such as Ocrevus for multiple sclerosis and Rituxan in immunology.
Table: Key Highlights of EpiBiologics
| Feature | Details |
|---|---|
| CEO and President | Ann Lee-Karlon, PhD |
| Founding Date | March 2023 |
| Initial Funding | $50 million (Series A), grew to $70 million |
| Primary Technology | EpiTACs (modular bispecific antibody-based system) |
| Categories of Degraders | AbTACs, KineTACs, TrainTACs |
| Tissue-Specific Focus | Reduces on-target toxicity and resistance mechanisms |
| Key Target | EGFR, ion channels, GPCRs |
| Year-End Goal | Nominate a candidate for an IND application |
EpiBiologics is well on its way to changing the landscape of protein degradation. With their innovative technologies and robust financial backing, they are set to make significant strides in targeting disease-driving proteins effectively.
