There are approximately 5.5 million new cases of cancer per year with RAS/MAPK pathway alterations, over 90% of which have limited or no treatment options. While the RAS/MAPK pathway has been well characterized and validated based on the development and approval of multiple compounds targeting discrete signaling nodes in the pathway, most of these compounds face resistance and tolerability challenges, highlighting the need for new approaches to target this important signaling cascade.
Our mission will involve delivering new therapies to patients in markets where there are limited or no approved therapies, which are referred to as “blue oceans” (Blue Ocean Strategy by Chan Kim & Renée Mauborgne), as well as markets where there are already approved product offerings, or “red oceans.” Of the approximately 5.5 million new patients diagnosed globally per year with cancers driven by RAS/MAPK pathway alterations, over 70% (approximately 4 million patients) are in blue oceans with limited or no treatment options.
|Alterations||GBM||HNSCC||NSCLC||CRC||Melanoma||PDAC||Other solid tumors||AML||US||EU||ROW||Global|
|BRAF Class 2||0.4||3.8||18||6.9||5.3||0.5||57||–||11||23||58||92|
|BRAF Class 3||0.1||0.9||12||17||2.5||–||29||0.2||6.1||15||40||61|
MAPK pathway alterations**
|Rest of World||109||555||635||964||60||264||1,053||57||3,696|
|Blue ocean opportunties||Red ocean opportunties|
|* Post-Osimertinib resistant population shown for EGFRm NSCLC except for SCLC transformation
** Co-occurring activating MAPK pathway alterations exclude EGFR overexpression Source: SEER database (2020), ECIS database (2020), GLOBOCAN database (2020), The AACR Project GENIE Consortium version 8.1 (2020), TCGA Research Network: https://www.cancer.gov/tcga, Tyner JW et al. (2018) PMID: 30333627, Brenner CW et al (2013) PMID: 24120142, Chen J et al. (2020) PMID: 32015526, and Ostrom QT, et al. (2020) PMID: 33123732
Our comprehensive clinical development plan enables us to address significant portions of patient populations across tissue-specific and tissue-agnostic indications.
|CRC||KRASwt, KRASm, NRASm, BRAFm|
|Pan tumor (tissue agnostic)||Remainder of ~5.5m patients with RAS/MAPK alterations|
Using innovative science and working with world-class collaborators, we are taking a holistic, modality-agnostic approach to effectively shut down the RAS/MAPK pathway. We are not just targeting individual signaling nodes. Rather, we seek to turn off multiple nodes and cooperative mechanisms along the pathway in parallel. To accomplish this, we are pursuing three therapeutic strategies that work together to comprehensively, and perhaps synergistically, shut down the RAS/MAPK pathway.
To learn more about our three therapeutic strategies and how they can help us overcome RAS/MAPK pathway-driven cancers, click on the numbers below.
with single agents and
clamp oncogenic drivers (MAPKlamp™) with combinations
with single agents and combinations with
and escape route targeted
enabled by other proteins
or pathways to further
Our strategic focus on the RAS/MAPK pathway allows us to comprehensively target every critical node in the pathway that could drive signaling. In fact, we currently have programs targeting each of the nodes colored in purple below.