Area of Focus
Corporate Targeted Protein Degradation
Publish Date
June 7, 2021
Nello Mainolfi, PhD, Co-Founder, President and CEO of Kymera Therapeutics

Marking Kymera’s 5-Year Anniversary

Kymera was founded with the mission to discover, develop, and commercialize transformative therapies while leading the evolution of a powerful new class of medicines based on targeted protein degradation (TPD). As we celebrate Kymera’s five-year anniversary, I look back and reflect on the inspiration and purpose behind Kymera’s founding, the progress we have made over these five years, and the work that is left to do.

Five years ago, I was drawn to the opportunity to build a once-in-a-generation type of company dedicated to exploring the promise of TPD, a novel therapeutic modality that has the potential to combine the power of genetic medicine with the benefits of small molecule-based technology. Several therapeutic modalities have been developed over the years to address aberrant disease-causing protein activity. These have included small molecule inhibitors of protein function, therapeutic antibodies, oligo-based therapeutics such as RNA interference therapeutics, antisense oligonucleotides, and cell and gene therapies. We believe that only approximately 20% of the full human proteome has been effectively drugged to date due to limitations of these therapeutic modalities. The discovery of ubiquitin-mediated TPD has revealed a new modality to harness the body’s natural protein recycling machinery to degrade disease-causing proteins in a potentially much broader way.

In founding Kymera with Atlas Venture, we saw a unique opportunity, not just to pioneer this novel drug class and open up a new therapeutic landscape, but also to rethink the boundaries of traditional drug discovery and development to build a company founded on a new modality to develop life-saving medicines. We decided to prioritize a long-term view of success and moved with a unique sense of urgency in the near-term to invest in areas that would allow us to deliver on the promise of TPD in two major ways.

The first is through building a platform that allowed us to evolve the technology to pursue translational hypotheses not addressed at that time, in order to generate a pipeline to fully realize the potential of TPD as a drug modality. The result of that work, our Pegasus™ platform, enables us to select the right E3 ligase for the right biological target, the right PKPD for the right disease population, and the right chemistry for the right protein target.

The other is around our target selection and pipeline evolution. We decided to go after undrugged, or not fully drugged, protein targets where TPD is the only unlocking technology within disease pathways with a high degree of validation. Our investments in the IL1R/TLR pathway with our IRAK4 and IRAKIMiD programs, and in the JAK/STAT pathway with our STAT3 programs, are examples of this target selection strategy, and we are excited about other pathways and programs that continue with this premise, which we will be disclosing in the near future. It is worth highlighting that the targets that we started from in the early incubation phase of the company are the ones that have progressed to, or on the cusp of, clinical-stage, validating our approach, commitment, and execution.

I like to think of Kymera’s first five years as a journey from idea generation to clinical entry. Thanks to our investments and further understanding of the technology, this is really only the first few steps of a long marathon in an effort to change the treatment of disease through the potential of TPD. It was a humbling experience to see our lead program, KT-474, a first-in-class IRAK4 protein degrader being developed for immune-inflammatory diseases, to initiate first-in-human dosing in only four years following the launch of the program, becoming the first heterobifunctional small molecule protein degrader outside of oncology to enter clinical development. We are also on our way to advancing our two lead degrader programs in oncology into the clinic this year, while expanding our pipeline of novel protein degraders, and continuing to broaden our platform and organizational capabilities.

Recently, we not only marked our five-year anniversary, but we also celebrated another important milestone – reaching our 100th employee. While we have ambitious goals to deliver on the promise of TPD and build a best-in-class company, we could not achieve this vision without our key asset – our people. As we have grown Kymera from 1 to 100, we have built a team of dedicated scientists and experienced drug hunters, as well as world-class operational and business talent, all committed to changing lives through the advancement of our science. The Kymera family is made of individuals that personify our key values, that are driven by solving big problems and working at the frontier of new chemistry, new biology, new clinical investigation, and doing so in a way that challenges the traditional status quo in science and operations. They are bold thinkers dedicated to tackling complex scientific challenges and being problem solvers with a shared purpose and mission. I am personally committed to fostering a company culture of transparency, inclusion, communication, problem solving, innovation, and a sense of urgency. Patients deserve this.

Much has changed over the last five years, including our transformation from a small team, growing into larger office space and labs, evolving into a publicly traded company, transitioning from discovery to clinical-stage, and successfully managing through the COVID-19 pandemic while still executing on our daily tasks, timelines, and broader mission. I remain humbled by the perseverance and commitment of our team. We have also received recognition over the years as a “Startup to Watch” by Chemical & Engineering News in 2018, named a “Fierce 15” biotechnology company by FierceBiotech in 2019, and more recently recognized as one of Boston’s “Best Places to Work” by the Boston Business Journal. We have also expanded our collaborations and partnerships from GSK to Vertex and Sanofi in order to expand our capabilities and accelerate our growth to becoming a fully integrated business. We have successfully funded the company based on execution against key de-risking inflection points to allow the flexibility for long-term strategic thinking and value creation. Further, we have continued to build out our leadership team with several key hires focused on growing and broadening our organizational capabilities to deliver on our mission.

Looking forward, 2021 promises to be another transformational year for Kymera, with two more expected entries into the clinic for novel therapeutic candidates designed to degrade intractable disease targets. This year, our focus will be in demonstrating the clinical potential for our lead programs with a goal of establishing our first proof-of-biology in humans by year-end. We also expect to expand our pipeline of innovative therapeutic candidates and advance our novel E3 ligase-enabled pipeline. This initiative of eliciting selective pharmacology in disease-relevant tissues, while sparing the ones that are negatively impacted, has long been considered a holy grail of drug development and would potentially transform therapeutic paradigms.

We have already achieved so much progress since our founding in 2016, but we recognize that patients and their families are waiting for breakthroughs to improve and save their lives. Over the next five years, we plan to further build on this foundation we have established, toward our goal of establishing Kymera as a fully integrated, best-in-class degrader medicines company with solutions that go well beyond TPD.

We dare to deliver on our science, innovation, and commitment to patients, and we are only just getting started on realizing our potential to truly impact disease through this new class of medicines.


Nello Mainolfi, PhD
Founder, President and Chief Executive Officer
Kymera Therapeutics