Advancing a Pipeline of Targeted Precision Oncology Therapeutics
Kinase inhibition is a proven approach to fighting cancer, and for nearly two decades has addressed an increasing number of oncology indications. At Kinnate, we employ a consistent, systematic approach to identify kinases that drive difficult-to-treat, genomically-defined diseases.
Through this approach, we aim to develop kinase inhibitor product candidates with therapeutic windows that provide durable and meaningful clinical responses to benefit patients in three patient populations:
- those with cancers that harbor known oncogenic drivers with no currently available targeted therapies;
- those with genomically well-characterized tumors that have intrinsic resistance to currently available treatments; and
- those whose tumors have acquired resistance over the course of therapy to currently available treatments.
By focusing on these three well-characterized patient populations, we believe that we will have a more efficient development path with a greater likelihood of success. Due to advancements in genomic profiling and relationships with our collaborating precision medicine cancer centers and leading research institutions, we have established and continue to develop a deep expertise and understanding of specific oncogenic drivers.
Our lead programs include candidates in preclinical development for cancers that are driven by specific oncogenic alterations in either the BRAF kinase gene, or in the FGFR2 and FGFR3 kinase genes. We are also advancing a number of other small molecule development programs, including a Cyclin-Dependent Kinase 12 (CDK12) inhibitor. To help advance these programs, Kinnate is working with leaders at experienced precision medicine cancer centers including Massachusetts General Hospital Cancer Center and the UC San Diego Moores Cancer Center.
“We look at cancer as having individual fingerprints or vulnerabilities and design programs that can penetrate those weak spots.”
– Eric Murphy, PhD, CSO & Co-Founder of Kinnate
A Focused Pipeline Portfolio
We have developed a proprietary kinase inhibitor portfolio of small molecule candidates advancing towards clinical studies.
- Phase 1
- Phase 2
- Phase 3
RAF | Preclinical
In our lead program, we are developing small molecule kinase inhibitors targeting specific classes of BRAF kinase mutations (Class II and Class III BRAF mutations) that characterize subsets of melanoma, lung cancer and other solid tumors. While three BRAF targeted kinase inhibitor drugs targeting the Class I BRAF mutations have been approved by the FDA, no targeted therapies have been approved for Class II or Class III BRAF mutation-driven cancers, unlike the Class I BRAF mutations where three BRAF targeted kinase inhibitor drugs have been approved by the FDA.
Patients with Class II or Class III BRAF mutations do not respond to existing targeted therapies, have few treatment options available to them and consequently have a poor prognosis. Initially, we plan to develop our lead RAF inhibitor candidates for the treatment of patients with melanoma and non-small cell lung cancer (NSCLC) subpopulations with Class II or Class III BRAF mutations that include specific BRAF point mutations (other than BRAF V600E), BRAF insertions/deletions (indels) and BRAF gene fusion events. We expect that our candidates may provide substantial clinical benefit to these cancer patients who are inadequately served by current therapies.
FGFR2/3 | Preclinical
We are developing small-molecule kinase inhibitors that target cancer-associated alterations in FGFR2 and FGFR3 genes, which (together with BRAF mutations) are among the most commonly identified oncogenic drivers detected in solid tumor cancers. Our FGFR candidates aim to address the initial alteration and clinically observed and predicted mutations in FGFR2 fusion gene-positive intrahepatic cholangiocarcinoma (ICC) and FGFR3-altered urothelial carcinoma (UC) that drive resistance to current FGFR2- and FGFR3-targeted therapies. In preclinical studies, we have observed inhibitory activity across a broad range of clinically-relevant mutations that drive acquired resistance. We believe that by addressing these mutations and broadly covering FGFR isoforms, we may be able to meaningfully increase the duration-of-response (DoR).
CDK12 | Preclinical
We are also advancing a number of other small molecule development programs, including a CDK12 inhibitor. CDK12 is an essential regulator of DNA damage response genes against which no targeted therapies are currently approved or, to our knowledge, in clinical development. We expect to develop a CDK12 candidate to target the treatment of ovarian carcinoma (OC), triple-negative breast cancer (TNBC) and metastatic castration-resistant prostate cancer (mCRPC). CDK12 along with our other small molecule development programs expand our penetration into cancer cases not covered by existing targeted therapies.
Novel Mechanisms | Discovery
We are actively engaged in discovery-stage programs investigating multiple undisclosed programs targeting key molecular drivers in cancer.
“Kinnate’s targeted approach will fill a significant unmet need and potentially bring better precision therapies to cancer patients. As an SAB member, I look forward to working closely with the Kinnate team to advance its pipeline of innovative kinase inhibitors.”
– Ezra Cohen, MD, FRCPSC, FASCO, Kinnate SAB Member