Kymera Therapeutics is a biotech company pioneering an emerging approach to cancer therapy called “targeted protein degradation.” Whereas most targeted therapies inhibit or inactivate the proteins or genes that drive the cancer, targeted protein degradation harnesses the body’s natural system of ridding itself of unwanted, ‘old’ or ‘broken’ components of cells. In March 2020, LLS made a strategic investment in Kymera’s work to treat blood-based cancers through our Therapy Acceleration Program, our venture philanthropy model through which we partner with biotech companies to advance promising therapies. Here, Kymera’s Chief Medical Officer Jared Gollob, M.D., discusses some of its lead programs with LLS:
Q. What is targeted protein degradation?
A. Protein degradation is a natural mechanism or process by which our body’s cellular machinery breaks down or degrades unwanted proteins. Scientists first uncovered this mechanism in the 1980s, and Drs. Aaron Ciechanover, Avram Hershko, and Irwin Rose were awarded the Nobel Prize for the discovery in 2004. Targeted protein degradation (TPD) is a new therapeutic modality that uses a small molecule “degrader” drug to chemically co-opt this innate cellular process toward specific disease-causing proteins.
Q. Why is TPD a promising new treatment approach for cancer?
A. Cancer is often caused by mutations or the over-production of specific proteins in the body. While conventional small molecule inhibitor drugs and antibody therapeutics have had a tremendous impact on the treatment of diseases, including cancer, it is estimated these traditional approaches have only be able to effectively drug approximately 20% of the full human genome to date. We believe TPD represents an opportunity to target a wide array of proteins that previously have been considered undruggable. This is very important in blood cancer, because we already know that many of the key proteins that drive these cancers have not been druggable with conventional approaches. Furthermore, protein degrader therapies are small molecule drugs that can be administered orally, or in pill-form, making them more broadly accessible for patients.
Q. LLS has invested in Kymera as part of our TAP program. What does this partnership mean for Kymera?
A. The Leukemia & Lymphoma Society has developed a reputation for investing in the most promising new therapeutic approaches, helping to deliver breakthrough therapies for patients. We are honored and delighted to be partnering with LLS to advance what we see as truly innovative therapeutics with the potential to transform cancer treatment for patients. This collaboration will further our research efforts and ensure patients have access to clinical studies and the latest information on our approach and medicines.
Q. Can you elaborate further on Kymera’s approach and relevant therapies in development?
A. Kymera is working at the forefront of TPD to invent new medicines for difficult-to-treat cancers, as well as for immune-inflammatory diseases. Our proprietary Pegasus drug discovery platform enables us to design potent, highly selective molecules that utilize the body’s natural protein degradation pathway, involving so-called “E3 ligases” (enzymes needed to tag a protein for disposal), to target and degrade disease-causing proteins. Pegasus combines our broad understanding of the localization and expression levels of the hundreds of E3 ligases in the human body with our proprietary E3 Ligase Binders Toolbox, as well as our chemistry, biology, and computational capabilities to develop protein degraders that address significant, unmet medical needs.
At this year’s American Association of Cancer Research (AACR) meeting, which took place virtually on June 22-24, we presented the first preclinical data on our novel IRAKIMiD degraders, showing robust antitumor activity in lymphomas with the MYD88-mutation, which constitute approximately one quarter of all diffuse large B-cell lymphomas (DLBCL). Also, at AACR, we shared new findings from our highly selective STAT3 degrader program – demonstrating potent antitumor activity in a solid tumor models not responsive to approved immunotherapies. This complements our previous data showing our STAT3 degraders are capable of driving tumor regression in animal models of STAT3-dependent blood-based cancers.
Q. What can we expect to see from Kymera in the next year?
A. Kymera is rapidly advancing our IRAKIMiD and STAT3 programs toward the clinic with plans to initiate Phase 1 studies in the second half of 2021. We will also continue to expand our pipeline of protein degrader therapies to treat additional blood-based and tissue-based cancers with high unmet medical need. We look forward to our continued partnership with LLS and to advancing new, potentially breakthrough medicines for patients.
Labs are eerily quiet. Clinical trials have been paused. Cancer researchers – particularly those who are early in their careers – are facing unprecedented uncertainty. The global COVID-19 pandemic has not only upended every aspect of cancer care for patients and their families, but also halted critical research around the world. In addition to lab closures, many institutions and organizations have been forced to scale back their investments in research, creating unexpected funding shortages. Without this funding, scientists risk shuttering their projects, which in turn, affects all of the laboratory staff who support them. And early-career researchers, often hit hardest by budgetary cuts, might be left with no option but to depart the field entirely – which would be a devastating loss of talent and ideas.
While these are trying times for us all, there is a bright spot: science is adapting and pressing forward. Here at The Leukemia & Lymphoma Society (LLS), we’re doing our part to support the most pioneering cancer research, during this new normal and beyond. Like many nonprofits, LLS is not immune to the damaging impact of COVID-19. Unfortunately, the economic realities of the crisis have caused LLS to reduce some of our research initiatives as well as patient support and education programs. Despite these challenges, we remain the largest nonprofit funder of blood cancer research, and we are committed to doing more for blood cancer patients and their families than any organization in the world.
As part of our efforts, LLS is finding new ways to drive forward lifesaving science. Many of these innovative approaches and funding mechanisms rely on collaboration, which is at the heart of the scientific community. After all, discoveries flow when there is teamwork, knowledge sharing and mentorship. And when you bring together researchers who are incredibly passionate about curing cancer – like every one of our researchers – progress is accelerated.
Here’s how LLS is working tirelessly to support cutting edge blood cancer research right now:
Just this week, the National Cancer Institute (NCI), part of the National Institutes of Health (NIH), announced the opening of emergency funding for current NCI-funded principal investigators whose postdoctoral research fellows have lost support from a nonprofit temporarily due to the pandemic. The emergency funding covers the fellow’s salary for up to six months and preserves continuity in training, which is essential for helping early-career researchers thrive in the field. LLS worked with the NIH to make this happen, and there are about 35 LLS-funded researchers who can benefit immediately from this program. Further, the program is open to all eligible postdoctoral cancer researchers nationwide. LLS sparked these conversations with the NIH, highlighting our shared commitment to retaining promising talent in cancer research. The result? An impactful funding opportunity for early-career researchers who need this support more than ever. Learn more here.
Recently, LLS announced the awarding of nine new grants through our Blood Cancer Discoveries Grant Program, in partnership with The Mark Foundation for Cancer Research and The Paul G. Allen Frontiers Group. This collaborative model of co-funding will help ignite the next breakthroughs by bolstering critical basic research and discovery by seasoned investigators. Learn more here.
This program builds on our previous collaborations with numerous institutions, non-profit foundations, and major donors to enable more than $70 million worth of research in the past seven years alone.
In addition to these initiatives, LLS continues to fund the most high-impact projects worldwide, including fueling the next generation of immunotherapy; continuing our attack on pediatric cancer; and driving forward more precision medicine for patients in urgent need, to name a few. We also continue to evaluate new opportunities with biotech companies to advance novel therapies through TAP, our venture philanthropy initiative.
Research is a beacon in the fight against cancer, illuminating the path toward better treatments and cures. At a time when we have witnessed incredible new blood cancer therapies – many of which have taken over a decade of laboratory research and clinical trials – we cannot afford for research to go dark or even let the lights dim. Thankfully, with the help of our donors, partners, volunteers, and supporters, as well as foundations, institutions and government agencies, we can keep the spotlight on advancing groundbreaking science.
After Spencer graduated from college in 2015, a friend noticed that he had very swollen lymph nodes on his neck.
As he sought medical advice, many healthcare professionals attributed his symptoms to being a side effect of a gender-affirming procedure he had a few months earlier (Spencer is a transgender man). It took several months and numerous appointments before he was diagnosed with stage three Hodgkin lymphoma.
When facing a cancer diagnosis, patients and their families suddenly are thrown into navigating the healthcare system – from making serious medical decisions to visiting multiple healthcare professionals. For many LGBTQI+ people, the critical questions about treatment options and recovery are followed immediately by concerns about social stigma, according to the National LGBT Cancer Network.
For Spencer, he was approached with questions that assumed a relationship between his cancer history and gender identity. Questions such as “Was this caused by your transition?” or “You’re an unusual case, huh?”
“This experience has driven my commitment to raise awareness and build the knowledge necessary for providers to embrace us as patients, honor our identities and protect our livelihood,” says Spencer.
Spencer went through 12 infusions of chemotherapy over six months followed by three months of recovery and is in remission today.