Targeted protein degrader drug innovators of note

Six companies enabling precision interventions for “undruggable” targets

Protein degraders have emerged as a major focus in pharma due to their potential to target diseases that have historically been difficult to treat, including oncology and autoimmune, inflammatory, neurodegenerative and infectious diseases. The field has been propelled by breakthroughs in understanding their mechanisms and the rise of proteolysis-targeting chimeras (PROTACs) and molecular glue degraders. As a result, pharma companies are increasingly incorporating protein degraders into their pipelines to expand treatment options and address unmet medical needs.

Over the past two decades, significant progress has been made in developing PROTACs and molecular glue degraders, though challenges remain with factors like protein-protein interaction predictability, cell permeability and oral bioavailability. Advances in computational modeling and artificial intelligence (AI) are helping overcome these barriers by streamlining discovery and optimization. Notably, a $6bn collaboration between XtalPi and DoveTree Medicines exemplifies how AI-driven drug discovery is accelerating the development of protein degraders across oncology, immunology, neurology and metabolic diseases. These innovations highlight how technology is shaping the future of the field.

The growing momentum is also reflected in the surge of high-value partnerships and licensing agreements. For example, Monte Rosa Therapeutics’ $5.7bn collaboration with Novartis on molecular glue degraders demonstrates the appetite of big pharma to invest in novel approaches. In 2024 alone, nearly 20 deals totalling more than $13bn were announced, underscoring the competitive and collaborative nature of this rapidly expanding space. Much of this activity stems from small, recently established biotech firms that are building proprietary discovery platforms and attracting partnerships with large pharma seeking to diversify pipelines.

On the clinical front, the field is beginning to achieve meaningful milestones. Arvinas and Pfizer’s new drug application for vepdegestrant (ARV-471) in advanced breast cancer marks the furthest advancement of a degrader into regulatory review, while Bristol Myers Squibb and Genentech are advancing PROTACs into phase 3 trials. Beyond oncology, innovation is extending to non-oncologic conditions such as androgenetic alopecia, where Kintor Pharmaceutical has reported promising phase 2 results. As more clinical evidence emerges, protein degraders are expected to transition from experimental therapies into mainstream precision medicine, with the potential to transform treatment landscapes across a broad spectrum of diseases.

It can be challenging to stay on top of the growing level of activity from the many companies working on different approaches and targets, often at very early stages, as well as the larger ecosystem of investors, partners and research centers supporting their work. To better understand the field and identify some of the promising innovators, Clarivate analysts reviewed data on deal valuations, clinical trials, patents and market approvals in the space to identify six targeted protein degrader Companies to Watch:

Beactica Therapeutics AB, headquartered in Uppsala, Sweden, is developing novel small molecule therapeutics through its Eclipsor™ platform to advance allosteric modulators and targeted protein degraders for diseases with high unmet need.
Kymera Therapeutics, is a clinical-stage biotech based in Watertown, Massachusetts that is developing oral small molecule protein degraders, with a focus on advancing transformative therapies for immunology, including the first degrader to make it into clinical trials for immunological diseases.
Monte Rosa Therapeutics, headquartered in Boston, Massachusetts, with operations in Basel, Switzerland, aims to advance a clinical pipeline of “only-in-class” molecular glue degraders to initially address autoimmune, inflammatory and oncologic diseases through its AI-driven QuEEN™ discovery engine.
Nurix Therapeutics Inc, based in Brisbane, California, is using its DEL-AI engine to advance a diversified, partnered pipeline of targeted protein degraders and degrader-antibody conjugates (DACs) for oncology and autoimmune and inflammatory diseases.
TRIANA Biomedicines, headquartered in Lexington, Massachusetts, has a platform that enables evaluation and prioritization of over 600 E3 ubiquitin ligases and their disease-relevant targets for the development of molecular glue degraders.
TRIMTECH Therapeutics, based in Cambridge, UK, is developing proprietary TRIMTAC® and TRIMGLUE® small molecule degraders designed to recruit TRIM21 for aggregate-selective degradation via the ubiquitin-proteasome system, to address neurodegenerative and inflammatory diseases.

The targeted protein degrader marketplace is expanding rapidly, including:

An increase in both deal value and volume over the past five years, according to Clarivate data, as pharmas recognize the potential of targeted protein degraders to change the treatment paradigm and aim to add the therapeutic modality to their pipelines;
A growing set of early-phase trials, as new companies enter the space and generate evidence for additional targets and overcome challenges with existing approaches.
Maturing regulatory environment for targeted protein degraders, as regulators gain additional experience with the review of safety and efficacy data for the targeted protein degraders reaching later-phase development.

For more insights into this exciting field of therapeutics and a deeper look at each of the six companies we’re keeping an eye on, please download the report, Targeted Protein Degrader Companies to Watch.