Deep Expertise in Chemistry and Structure-based Drug Design Drives Pipeline of Highly Selective Compounds

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 have a highly experienced drug hunting team to advance novel programs into the clinic that are differentiated, and target validated drivers. We focus on four key parameters in our molecule design: high selectivity, optimized pharmaceutical properties, broad alteration coverage including overcoming resistance or achieving brain penetrance.

Through this approach, we aim to develop 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 well-characterized patient populations, we believe 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.

A Focused Pipeline

We have developed a proprietary portfolio of small molecule candidates targeting validated drivers of cancer.

RAF / exarafenib Monotherapy

Phase 1b

Exarafenib (KIN-2787) is an orally administered, potent and selective investigational small molecule pan-RAF inhibitor. KN-8701 is an ongoing, global Phase 1 clinical trial (NCT04913285) evaluating exarafenib in patients with advanced solid tumors harboring BRAF-altered and/or who have NRAS mutant melanoma. KN-8701 contains a two-part dose escalation: Part A1 evaluated exarafenib as a monotherapy across BRAF alterations and tumor types, and Part A2 is evaluating exarafenib in combination with binimetinib, a MEK inhibitor. Part B, dose expansion, is evaluating exarafenib monotherapy at 300 mg bid in patients with BRAF-altered cancers including lung cancer, melanoma and other solid tumors.

BRAF-Driven Advanced Adult Solid Tumors

Exarafenib Monotherapy
Pan-RAF

RAF / exarafenib Combination

Phase 1a

Advanced NRAS Mutant Melanoma

Exarafenib Combination
Pan-RAF

Exarafenib (KIN-2787) is an orally administered, potent and selective investigational small molecule pan-RAF inhibitor. Unlike currently available treatments that target only Class I BRAF kinase mutations, exarafenib is designed to target BRAF Class II and Class III alterations, where it has the potential to be a first-line targeted therapy, in addition to covering BRAF Class I alterations, and as a potential treatment for NRAS mutation-positive melanoma. KN-8701 is an ongoing, global Phase 1 clinical trial (NCT04913285) evaluating exarafenib in patients with advanced solid tumors harboring BRAF Class I, II and III alterations, and/or who have NRAS mutant melanoma. KN-8701 contains a two-part dose escalation: Part A1 is evaluating exarafenib as a monotherapy across BRAF alterations and tumor types, and Part A2 is evaluating exarafenib in combination with binimetinib, a MEK inhibitor. Part B, dose expansion, is evaluating exarafenib at the recommended dose and schedule in patients with BRAF-altered cancers including lung cancer, melanoma and other solid tumors1.

FGFR2/3 / KIN-3248

Phase 1a

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). We are currently evaluating the safety and tolerability of KIN-3248 in a first-in-human dose-escalation study in adults with advanced tumors harboring FGFR2 and/or FGFR3 gene alterations. More information can be found at ClinicalTrials.gov at: https://clinicaltrials.gov/ct2/show/NCT05242822.

Naïve + Pre-treated FGFR2/3 Driven Advanced Adult Solid Tumors

KIN-3248
FGFR2/3- Driven

KIN-7136

IND-Enabling

KIN-7136 is designed to be a next generation brain-penetrant MEK inhibitor for investigation in advanced adult solid tumors, primarily non-small cell lung cancer (NSCLC), that are MAPK pathway-driven, including those with brain metastases. Kinnate expects to enter the clinic with KIN-7136 in the second half of 2023, pending U.S. Food and Drug Administration (FDA) clearance on its investigational new drug (IND) application. The goal of the Phase 1 clinical trial will be to establish safety and tolerability, and generate understanding of the pharmacokinetics, pharmacodynamics and early clinical activity of KIN-7136 as a monotherapy. In parallel, the company intends to evaluate KIN-7136 combined with exarafenib, Kinnate’s investigational pan-RAF inhibitor. Kinnate plans to prioritize exploring the KIN-7136 and exarafenib combination in BRAF Class I patients with NSCLC that have been previously treated with a RAF inhibitor and patients with NRAS mutant melanoma. This approach enables access to a potentially broader patient population to be evaluated with exarafenib, including those with brain metastases. KIN-7136 may serve as part of the company’s long-term RAF combination strategy.

MAPK-Driven Advanced Adult Solid Tumors

KIN-7136
Brain Penetrant MEK

KIN-8741

IND-Enabling

Research has shown that acquired resistance to approved and in-development c-MET inhibitors limits clinical benefit. Up to 35% of patients treated with approved c-MET inhibitors develop on-target resistance mutations, leaving them with limited treatment options and a poor prognosis. In patients with NSCLC, about 3-4% of patients present with actionable MET exon 14 alterations. KIN-8741 is designed to be a highly selective c-MET inhibitor with broad mutational coverage, including acquired resistance mutations, across a variety of solid tumors in which c-MET is overexpressed, such as NSCLC. Kinnate expects to enter the clinic with KIN-8741 in the first half of 2024, pending FDA clearance on its IND application.

c-Met-Driven Advanced Adult Solid Tumors

KIN-8741
c-MET, Covers Acquired Resistance

CDK12 / KIN004

Discovery

Kinnate is exploring strategic alternatives for its CDK12 program.

Adult Solid Tumors

KIN004
CDK12

“Kinnate’s targeted approach will fill a significant unmet need and potentially bring better precision therapies to patients with cancer. 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