TPD – Targeted Elimination of Disease Causing Proteins

Targeted protein degradation (TPD) is an emerging therapeutic modality that has the potential to enable the treatment of difficult-to-treat diseases. While conventional medicines, such as small molecule inhibitors and monoclonal antibodies, address fewer than 20% of the proteome, TPD offers a unique means to tap into the rest of the vast, unexplored proteome. Through TPD, a disease can be addressed by controlling the amount of a harmful protein rather than trying to modulate or inhibit its function. The control of protein levels is accomplished with a small molecule drug, called a protein degrader. TPD is a bifunctional small molecule that recruit E3 ubiquitin ligases to the protein of interest and mediate its ubiquitination and subsequent proteolysis by the proteasome.

Small molecule-mediated selective TPD has several advantages over traditional drug discovery strategies. One of the primary advantages is the high degree of target specificity that can be rapidly validated by leveraging the multiple layers of selectivity in the cellular machinery. Moreover, owing to the fact that the degrader molecules cannot be destroyed, they can cause the destruction of many copies of the harmful protein and reduce systemic drug exposure. In addition, it can counteract increased target protein expression by inhibiting the protein function. It is worth noting that a single protein degrader has the ability to potentially eliminate multiple disease-causing proteins through proteasome degradation of the target protein. However, an inhibitor drug can only block a single disease-causing protein at a time. The following figure highlights the difference between a TPD and a protein inhibitor.

Target Protein Degradation- Transformative Approach
difference between a protein degrader and a protein inhibitor

TPD represents a new class of chemical tools that have the power to ablate all the functions of a drug target at once, including scaffolding and catalytic functions which are difficult to target with small molecule inhibitors. This shift from inhibition of the target protein to its removal gives a greater degree of temporal control and provides therapeutic options that extend beyond the druggable target space. Various type of protein degraders are mentioned in the figure. 

It is important to note that in contrast to the traditional small molecule inhibitors and antibody drugs, protein degraders are designed to develop drug candidates for many intractable diseases that other therapeutic modalities cannot address. Furthermore, various factors, such as technological advancements, growing interest and extensive research, and rise in partnering activity and capital investments, in this sector would continue to be a huge contributing force towards the progression of this niche market. These promising developments and an in-depth analysis of the essential obstacles could result in this technology to be increasingly implemented across multiple therapeutic areas.

TPD based Drugs and Technologies- Current Market Landscape

During our research, we identified around 150 unique TPD – based therapeutics and more than 40 target protein degradation enabling technologies.

Target Protein Degradation- Transformative Approach - sample list of drugs and technology platforms Roots Analysis

Most of the pipeline candidates are in the early phases of development, and predominantly designed to target diverse types of cancers; majority of the drug candidates are designed for administration via non-invasive routes.

Want additional details on the pipeline? It is just a click away.

Which geographies are the most active in conducting clinical trials on TPD – based therapeutics?

According to our research, till January 2021, the maximum number of patients (close to 3,600) were observed to have been enrolled in trials conducted in North America, accounting for about 42% of the total enrolment in trials of TPD – based interventions.

Prominent scientists / medical research professionals, who have been actively involved in clinical research related to targeted protein degraders, are presently considered key opinion leaders in this domain.

Key Opinion Leader KOL mapping for Target Protein Degradation Market by Roots Analysis

Which are the leading administering institute centers supporting the research related to this domain?

Several organizations have extended financial support to aid research efforts in this domain; currently, the focus, in terms of funds disbursed, is primarily to support investigation of drugs intended for treating cancer. As is evident from the figure, majority of grants were / are being managed by NCI. This is followed by grants managed by NIAID (17%) in the given time period. Other active administrating institutes include NIDDK, NHLBI, NINDS and NIGMS.

How has the intellectual property landscape in this market evolved over the years?

Over time, more than 14,500 patents related to TPD technologies have been filed / granted to various industry and non-industry players, indicating the rising level of R&D activity in this field. During the given time period, majority of the patents (7,955) were filed / granted in North America. Within this region, the maximum number of patents (7,882) have been filed in the US. This is followed by Europe where 4,508 patents were filed / granted. The number of patents is indicative of the significant amount of research activity taking place in these regions.

What kind of partnership models are commonly adopted by industry stakeholders?

In the past few years, a number of stakeholders engaged in this domain have partnered with various industry players / research institutes for the development of small molecule degraders in order to selectively eliminate disease-causing proteins.

What is the trend of capital investments in the targeted protein degradation market?

Foreseeing a lucrative future, private and public investors have invested over USD 5 billion, across 130+ instances, into firms involved in the development of protein degrader therapies.

Which is the valuable structure model for the licensing deals in the field of targeted protein degradation?

Our proprietary deal structure model suggests that IP owners should adopt a scenario-based approach to identify the most optimum / valuable deal structure while licensing their technology.

How is the current and future market opportunity likely to be distributed across key market segments?

We expect the revenues generated from the licensing of technologies, designed for developing targeted protein degradation-based therapeutic products, are likely to increase significantly from USD 392 million in 2021 to USD 3,285 million by 2030. The significant rise in targeted protein degradation market value can be attributed to the fact that a number of drugs developed using the licensed Targeted protein degradation enabling technologies are anticipated to be launched in 2029, making the technology developers eligible for milestone payments.

Among various types of therapeutic areas, targeted protein degradation-based therapeutics and technologies market is majorly contributed to oncological disorders, followed by the neurological disorders.

Our estimates suggest that North America is likely to contribute majorly (58%) in the targeted protein degradation-based therapeutics and technologies market by 2030. Further, Europe is anticipated to capture 34% in the coming decade.

For more details, you can also download the SAMPLE REPORT on TPD by Roots Analysis.