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:

    1. those with cancers that harbor known oncogenic drivers with no currently available targeted therapies;
    2. those with genomically well-characterized tumors that have intrinsic resistance to currently available treatments; and
    3. 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.

Kinnate has a broad pipeline with multiple programs targeting validated oncogenic drivers. Our lead program, KIN-2787 is currently in clinical trials and is focused on cancers that are driven by specific oncogenic alterations in the BRAF kinase gene not served by approved therapies. We are also advancing our preclinical FGFR program (KIN-3248) targeting a significant unmet need of resistance to current FGFR inhibitors as well as 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.

A Focused Pipeline Portfolio

We have developed a proprietary kinase inhibitor portfolio of small molecule candidates targeting genomically defined cancers.

RAF / KIN-2787

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. 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 KIN-2787 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 KIN-2787 may provide substantial clinical benefit to these cancer patients who are inadequately served by current therapies. We are currently evaluating the safety and tolerability of KIN-2787 in a first-in-human dose-escalation study in adults with BRAF-mutated advanced or metastatic solid tumors. More information can be found on ClinicalTrials.gov at: https://www.clinicaltrials.gov/ct2/show/NCT04913285

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FGFR2/3 / KIN-3248

Our FGFR program, KIN-3248 is a small-molecule kinase inhibitor that target cancer-associated alterations in FGFR2 and FGFR3 genes, which are among the most commonly identified oncogenic drivers detected in solid tumor cancers. KIN-3248 aims to address the primary driver-alteration and clinically observed and predicted FGFR 2/3 mutations that drive resistance to current FGFR2- and FGFR3-targeted therapies in intrahepatic cholangiocarcinoma (ICC) and urothelial carcinoma (UC). 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).

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CDK12 / KIN004

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.

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Undisclosed Targets

We are actively engaged in discovery-stage programs investigating multiple undisclosed programs targeting key molecular drivers in cancer.

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“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