Kymera Therapeutics, based in Cambridge, Massachusetts, entered a strategic collaboration deal with Paris-based Sanofi. They will focus on developing and commercializing protein degrader therapies that target IRAK4 in immune-inflammatory diseases, such and rheumatoid arthritis.
Under the terms of the deal, Sanofi is paying Kymera $150 million up front for global rights to develop the company’s IRAK4 protein degraders in indications for inflammation and immunology, as well as a second earlier stage program that has not been disclosed. There is an additional $2 billion in potential development, regulatory and sales milestones. Kymera is also eligible for royalties on commercial products coming out of the partnership.
IRAK4 is understood to play a big role in multiple immune and inflammatory diseases, such as rheumatoid arthritis, atopic dermatitis and hidradenitis suppurativa. Hidradenitis suppurativa is a skin condition that causes small, painful lumps to form under the skin.
Kymera will advance the IRAK4 program into the clinic for Phase I trials. Sanofi will take over clinical development and commercialization at that point. Sanofi is going to run clinical development for the second program. Kymera holds the option to participate in the development of both programs in the U.S. during clinical development and will retain global rights to its IRAK4 program in cancer.
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“This is an important collaboration for both companies and for the field of targeted protein degradation,” said Nello Mainolfi, co-founder, president and chief executive officer of Kymera. “Kymera is becoming a fully integrated biotechnology company advancing a pipeline of novel therapies with the potential to transform treatment paradigms. We are excited to partner with Sanofi, an organization with world-class drug development and commercialization capabilities, to ensure maximal patient impact from two of our programs across multiple disease indications, while enabling Kymera to invest in key strategic areas to realize the broad potential of protein degrader therapies.”
IRAK4 is a protein involved in inflammation mediated by the activation of toll-like receptors (TLRs) and IL-1 receptors. Both types of signaling by way of IRAK4 participates in the normal immune response. But abnormal activation of the pathways is linked to multiple immune-inflammatory diseases.
In preclinical evaluations, Kymera demonstrated oral daily doses of an IRAK4 degrader can completely knock down IRAK4 in skin and immune cells in “higher species” and appears to be well tolerated. In in vitro and in vivo tests, the drugs demonstrated potent anti-inflammatory activity.
“Targeted protein degradation is an exciting modality,” said John Reed, Global Head of Research & Development at Sanofi. “Kymera has developed an incredible drug discovery engine producing protein degraders with compelling and differentiated pharmacology against targets that, to date, have not been optimally addressed with other therapeutic modalities. We are excited to partner with the Kymera team to advance a new generation of first-in-class therapies with the potential to eliminate underlying drivers of disease.”
Yesterday, Sanofi announced it had inked a $987 million deal with Amsterdam-based Kiadis Pharma. Sanofi licensed an undisclosed K-NK0004 program, covering Kiadis’ proprietary CD38 knockout (CD38KO) K-NK therapeutics for combination with anti-CD38 monoclonal antibodies. Sanofi’s Sarclisa was recently approved for multiple myeloma and is an anti-CD38 monoclonal antibody. Sanofi also picked up rights to use Kiadis’ K-NK platform for two unidentified preclinical programs.
NK cells are the first of the human body’s immune cells to respond against cancer and infections. Antibodies team with NK cells to kill cancer cells in what is called antibody-dependent cell-mediated cytotoxicity (ADCC). Treating multiple myeloma with anti-CD38 antibodies, like Sarclisa, depletes the patients’ own NK cells because natural NK cells also express CD38.
Sanofi has a long relationship with Kymera going back to the French company’s investment in Kymera’s Series B financing round. They were discussing the possibility of additional research-and-development work prior to the COVID-19 pandemic, and completed the discussions via video conferencing.