exarafenib (KIN-2787) / Pierre Fabre - LARVOL DELTA

Results from a Phase I trial evaluating exarafenib in NRAS-mutant melanoma (YouTube) - "Janice Mehnert, MD...shares the results from a Phase I KN-8701 trial (NCT04913285) of exarafenib, a selective pan-RAF inhibitor, as monotherapy and in combination with binimetinib in NRAS-mutant melanoma. Promising responses were reported in patients receiving exarafenib, which was also tolerable when combined with binimetinib in most patients with NRAS-mutant melanoma. This interview took place at the Society for Melanoma Research (SMR) 2024 Annual Meeting in New Orleans, LA."

Interview • Video

A Phase 1 Clinical Trial Evaluating Exarafenib, a Selective Pan-RAF lnhibitor, as monotherapy and in combination with Binimetinib in NRAS-mutant (NRASMut) Melanoma (Mel) (SMR 2024) - No abstract available

Clinical • Combination therapy • Late-breaking abstract • Monotherapy • P1 data • Melanoma • Oncology • Solid Tumor

A phase I clinical trial evaluating exarafenib, a selective pan-RAF inhibitor in combination with binimetinib in NRAS-mutant (NRASMut) melanoma (Mel) & BRAF-altered solid tumors (ESMO 2024) - P1 | "Ex + B can be safely administered, achieve meaningful drug exposures & show promising activity in NRASMut Mel & BRAF Cl. II fusion-driven cancer pts. Pt enrollment continues under Pierre Fabre sponsorship ahead of a planned expansion phase."

Clinical • Combination therapy • P1 data • Melanoma • Oncology • Solid Tumor • BRAF • NRAS

Exarafenib in NRAS mutant solid tumors -33% ORR. Remains an unmet need, especially in melanoma. Glad to see progress in this area.

A Study to Evaluate KIN-2787 in Participants With BRAF and/or NRAS Mutation Positive Solid Tumors (clinicaltrials.gov) - P1 | N=400 | Recruiting | Sponsor: Pierre Fabre Medicament | Trial completion date: Jun 2024 ➔ Dec 2025 | Trial primary completion date: Mar 2024 ➔ Dec 2024

Trial completion date • Trial primary completion date • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • BRAF • NRAS

Kinnate Biopharma Inc. Sells Its Investigational Pan-RAF Inhibitor, Exarafenib, to Pierre Fabre Laboratories (GlobeNewswire) - "Kinnate Biopharma Inc...and Pierre Fabre Médicament, SAS (“Pierre Fabre Laboratories”), a global player in oncology, today announced their agreement to the sale of the Company’s investigational pan-RAF inhibitor, exarafenib, and other pan-RAF program assets pursuant to the APA entered into by the parties. The sale of global rights is in furtherance of the Company’s previously announced exploration of strategic alternatives...Under the terms of the APA, Pierre Fabre Laboratories has purchased exarafenib and other pan-RAF assets and will assume 100% of the ongoing program and costs associated with these assets. In consideration, Kinnate will receive a total consideration of up to $31 million, consisting of $500,000 at closing, and a $30.5 million payment, contingent upon the earlier of the dosing of the first patient in the first pivotal trial for exarafenib or any other acquired asset..."

Licensing / partnership • Oncology • Solid Tumor

Kinnate Biopharma Inc. Enters into Agreement to be Acquired by XOMA Corporation for Between $2.3352 and $2.5879 Per Share in Cash, Plus One Contingent Value Right per Share (GlobeNewswire) - "Kinnate Biopharma...announced it has entered into a definitive merger agreement...whereby XOMA Corporation ('XOMA') will acquire Kinnate for a price per share of Kinnate common stock...of between $2.3352 and $2.5879 in cash, consisting of (i) a base cash price of $2.3352 per share and (ii) an additional cash amount of up to $0.2527 per share, plus one non-transferable contingent value right per share, representing the right to receive (a) 100% of the net proceeds payable from any disposition of the Company’s investigational pan-RAF inhibitor, exarafenib, and/or any other pan-RAF inhibitors prior to the closing of the merger transaction and (b) 85% of the net proceeds payable from any disposition of other Kinnate assets entered into prior to, or within one year from, closing and received within five years of closing pursuant to a definitive contingent value rights agreement....The merger transaction is expected to close in the first half of 2024."

M&A • Solid Tumor

The Discovery of Exarafenib (KIN-2787): Overcoming the Challenges of Pan-RAF Kinase Inhibition. (PubMed, J Med Chem) - "However, the discovery of a potent and selective inhibitor with biopharmaceutical properties suitable to sustain robust target inhibition in the clinical setting has proven challenging. Herein, we report the discovery of exarafenib (15), a highly potent and selective inhibitor that intercepts the RAF protein in the dimer compatible αC-helix-IN conformation and demonstrates anti-tumor efficacy in preclinical models with BRAF class I, II, and III and NRAS alterations."

Journal • Colorectal Cancer • Gastrointestinal Cancer • Melanoma • Oncology • Solid Tumor • BRAF • NRAS

A Study to Evaluate KIN-2787 in Participants With BRAF and/or NRAS Mutation Positive Solid Tumors (clinicaltrials.gov) - P1 | N=400 | Recruiting | Sponsor: Kinnate Biopharma | N=262 ➔ 400

Enrollment change • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • BRAF • NRAS

Kinnate Biopharma Inc. Announces Pipeline Updates, Strategic Reprioritization and Workforce Restructuring (GlobeNewswire) - P1/1b | N=262 | NCT04913285 | Sponsor: Kinnate Biopharma | "As of September 11, 2023, the data cutoff, a total of 107 patients were enrolled in the monotherapy arm....Out of 8 patients with Class II fusion-driven solid tumors who received exarafenib at 300 mg bid, 3 showed radiographic tumor reductions, 2 of the 6 efficacy-evaluable patients achieved confirmed PRs, resulting in a 33% ORR, and the remaining 4 efficacy-evaluable patients achieved SD as their best response, yielding a 100% DCR. Among 13 patients with Class II non-fusion driven solid tumors treated with exarafenib at 300 mg bid, 7 patients experienced radiographic tumor reductions and 6 patients experienced SD as their best response, yielding a DCR of 60%. In addition, 1 patient treated at the 200 mg bid dose experienced a confirmed PR....Kinnate will not proceed with further clinical development of exarafenib as a monotherapy agent and will explore strategic alternatives."

Discontinued • P1 data • Oncology • Solid Tumor

Kinnate Biopharma Inc. Announces Pipeline Updates, Strategic Reprioritization and Workforce Restructuring (GlobeNewswire) - P1/1b | N=262 | NCT04913285 | Sponsor: Kinnate Biopharma | "As of September 11, 2023, the data cutoff, 44 patients with NRAS mutant melanoma and BRAF-altered solid tumors were enrolled across 6 exarafenib plus binimetinib combination dose cohorts, including 24 patients who continue on therapy....Among 16 efficacy-evaluable patients with NRAS mutant melanoma who had not received prior RAF, MEK, or ERK inhibitors, 6 achieved confirmed and unconfirmed partial responses (PRs), resulting in a 38% overall response rate (ORR), with 5 additional patients experiencing stable disease (SD) as their best response, yielding a 69% disease control rate (DCR)....In the fourth quarter of 2023, the Company intends to select two doses for further development."

P1 data • Melanoma • Oncology • Skin Cancer • Solid Tumor

Kinnate Biopharma Inc. Reports First Quarter 2023 Financial Results and Recent Corporate Updates (GlobeNewswire) - "Pipeline Updates:...(i) The company expects to provide an update in the second half of 2023 on the dose selection and additional escalation data for exarafenib plus binimetinib, and initial exarafenib monotherapy dose expansion data in the first half of 2024; (ii) A brain penetrant mitogen-activated protein kinase (MEK) inhibitor (KIN-7136), expected to enter the clinic in the second half of 2023."

New trial • P1 data • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Skin Cancer • Solid Tumor • Thoracic Cancer

First Report of Positive Dose Escalation Data Supports Best-in-Class Profile for Investigational Exarafenib as a Single Agent and in Combination with Binimetinib in BRAF-altered Cancers and NRAS Mutant Melanoma (GlobeNewswire) - P1 | N=155 | NCT04913285 | Sponsor: Kinnate Biopharma | "Kinnate Biopharma...announced positive monotherapy dose escalation data for its investigational, highly selective and potent pan-RAF inhibitor, exarafenib, from Part A1 of its ongoing global Phase 1 KN-8701 clinical trial....'The exarafenib dose escalation data provide striking proof of concept for a monotherapy pan-RAF inhibitor,' said Alexander Spira..."

P1 data • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor

A Study to Evaluate KIN-2787 in Participants With BRAF and/or NRAS Mutation Positive Solid Tumors (clinicaltrials.gov) - P1 | N=262 | Recruiting | Sponsor: Kinnate Biopharma | N=155 ➔ 262

Enrollment change • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor • BRAF • NRAS

Exarafenib (KIN-2787) is a potent, selective pan-RAF inhibitor with activity in preclinical models of BRAF class II/III mutant and NRAS mutant melanoma (AACR 2023) - P1 | "The superior kinome selectivity of exarafenib and its activity across multiple RAF-dependent melanoma models position it as a potentially class-leading pan-RAF inhibitor. In addition to efficacy in BRAF mutant tumors, these data support use of exarafenib in combination therapy with MEK inhibitors in NRAS mutant melanoma. A Ph I dose escalation clinical trial evaluating the safety and efficacy of exarafenib in monotherapy and in combination with binimetinib is ongoing (NCT04913285)."

Preclinical • Melanoma • Oncology • Solid Tumor • BRAF • NRAS

A Phase 1 Clinical Trial Evaluating Monotherapy With Exarafenib (KIN-2787), a Highly Selective Pan-RAF Inhibitor, in BRAF‑Altered Solid Tumors and NRAS-Mutant Melanoma (OncLive) - "Alexander I. Spira, MD, PhD, shares new dose escalation data from the first-in-human Phase 1 KIN-2787 study of the pan-RAF inhibitor exarafenib in patients with BRAF-altered solid tumors or NRAS-mutant melanoma."

Video

Trials in progress: a global phase 1/1b clinical trial evaluating exarafenib (KIN-2787), a highly selective pan-RAF inhibitor, in adult patients with BRAF-altered solid tumors and NRAS mutant melanoma (AACR 2023) - P1 | "Exarafenib achieves therapeutically meaningful drug exposures and demonstrates promising tolerability & clinical activity in BRAF or NRAS alteration-driven solid tumors. Pt enrollment & exarafenib treatment at 300 mg bid continues."

Clinical • P1 data • Melanoma • Oncology • Solid Tumor • BRAF • NRAS

First Report of Positive Dose Escalation Data Supports Best-in-Class Profile for Investigational Exarafenib as a Single Agent and in Combination with Binimetinib in BRAF-altered Cancers and NRAS Mutant Melanoma (GlobeNewswire) - P1 | N=155 | NCT04913285 | Sponsor: Kinnate Biopharma | "Kinnate Biopharma...announced positive monotherapy dose escalation data for its investigational, highly selective and potent pan-RAF inhibitor, exarafenib, from Part A1 of its ongoing global Phase 1 KN-8701 clinical trial. These results will be featured in an oral presentation today at 3:35 p.m. ET during the Clinical Trials Mini Symposium Session at the American Association for Cancer Research (AACR) 2023 Annual Meeting....The ORR in patients with BRAF Class II alterations was 33% (1 of 3) at 300 mg bid, which included a patient with non-small cell lung cancer (NSCLC) harboring a BRAF Class II fusion."

P1 data • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Antitumor activity of KIN-2787, a next-generation pan-RAF inhibitor, in preclinical models of human RAF/RAS mutant melanoma (AACR 2022) - P1 | "In contrast to vemurafenib, an approved BRAF inhibitor with activity limited to Class I BRAF alterations, KIN-2787 was active across all classes of BRAF mutant melanoma cells (EC50 values < 100 nM)...Additionally, KIN-2787 was efficacious in a pre-/post-treatment melanoma PDX pair in which the original tumor was Class I BRAF V600E but acquired a Class II BRAF kinase domain duplication upon progression on dabrafenib + trametinib... KIN-2787 is a next-generation, pan-RAF inhibitor with in vitro and in vivo activity against human melanoma driven by BRAF and/or NRAS mutations. Data supports KIN-2787 use in acquired BRAF dimer-dependent resistance to BRAF+MEK inhibitor therapy. A Phase I dose escalation and expansion clinical trial evaluating the safety and efficacy of KIN-2787 is ongoing (NCT04913285)."

Preclinical • Melanoma • Oncology • Solid Tumor • KRAS • NRAS

Antitumor Activity of KIN-2787, a Next-Generation pan-RAF Inhibitor, in Preclinical Models of Human BRAF-alteration Driven Non-small Cell Lung Cancer (NSCLC) (IASLC-TTLC 2022) - P1 | "While the RAF inhibitor dabrafenib is approved for treatment of BRAF Class I-altered NSCLC (in combination with trametinib), there are no RAF targeted therapies for treatment of NSCLC patients with tumors driven by BRAF Class II or Class III dimer-dependent alterations, likely contributing to the inferior clinical outcomes of these patients (Dagogo-Jack et al...In contrast to dabrafenib or vemurafenib, approved BRAF inhibitors with activity limited to Class I BRAF alterations, KIN-2787 was most active in Class II and Class III BRAF mutant NSCLC cells (EC50 median values 264 nM and 24 nM, respectively)...A Phase I dose-escalation and expansion clinical trial evaluating the safety and efficacy of KIN-2787 is actively enrolling (NCT04913285). Patients with advanced and metastatic solid tumors, including NSCLC patients, whose cancers are driven by BRAF Class I, II, or III alterations will receive KIN-2787 treatment on this study."

Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • BRAF • KRAS • NRAS

Kinnate Biopharma Inc. Provides Full-Year 2022 Financial Results and Recent Corporate Updates (GlobeNewswire) - "...'2023 is shaping up to be a transformational year for Kinnate, one with several key clinical readouts anticipated, including the first monotherapy data disclosure on our lead product candidate, exarafenib, in an oral presentation at the upcoming AACR conference, initial data for the exarafenib plus binimetinib combination in the first half of 2023 and initial dose escalation data from our FGFR program, which is expected in the second half of this year'..."

P1 data • Oncology • Solid Tumor

Antitumor activity of KIN-2787, a next-generation pan-RAF inhibitor, in combination with MEK inhibition in preclinical models of human NRAS mutant melanoma. (ASCO 2022) - P1 | "KIN-2787 is a highly selective, potent, next-generation, pan-RAF inhibitor with activity across BRAF and RAS mutant human tumor cell models. Preclinical in vitro and in vivo studies using KIN-2787 in combination with binimetinib demonstrated significant combination benefit in NRAS mutant melanoma models. Taken together with its unique selectively, these data support use of KIN-2787 in combination therapy in this patient segment."

Combination therapy • Preclinical • Melanoma • Oncology • Solid Tumor • BRAF • DDR1 • KRAS • NRAS

Kinnate Biopharma Inc. to Report First Clinical Data for Its Investigational Pan-RAF Inhibitor, Exarafenib (KIN-2787), in an Oral Presentation at the AACR 2023 Annual Meeting (GlobeNewswire) - "Kinnate Biopharma...announced that a clinical trial abstract for its investigational pan-RAF inhibitor exarafenib has been selected for an oral presentation during the Clinical Trials Mini Symposium Session at the American Association for Cancer Research (AACR) 2023 Annual Meeting...The oral presentation represents the first report of safety and clinical efficacy data from the monotherapy dose escalation portion of KN-8701, an ongoing global Phase 1 clinical trial evaluating exarafenib in patients with BRAF-altered solid tumors and NRAS mutant-positive melanoma. The company also announced that it has initiated enrollment of patients into the monotherapy dose expansion cohorts of KN-8701....Separately, new preclinical data for exarafenib monotherapy and in combination with a MEK inhibitor in human NRAS mutant melanoma models will be presented in a poster session."

Enrollment status • P1 data • Preclinical • Melanoma • Oncology • Skin Cancer • Solid Tumor • BRAF • NRAS

[VIRTUAL] Design and rationale of a first in human (FIH) Phase 1/1b study evaluating KIN-2787, a potent and highly selective pan-RAF inhibitor, in adult patients with BRAF mutation positive solid tumors (AACR-NCI-EORTC 2021) - No abstract available

Clinical • P1 data • Oncology • Solid Tumor • BRAF

Kinnate Biopharma Inc. Announces Acquisition of Ownership Stake from Series A Investors of the China Joint Venture, Kinnjiu Biopharma Inc., and Initiation of Phase 1 Clinical Trial for Exarafenib (KIN-2787) in People's Republic of China (GlobeNewswire) - "Kinnate Biopharma...announced that it has acquired ownership stake of Kinnjiu Biopharma Inc. ('Kinnjiu') previously held by the Series A investors using a combination of Kinnate shares and cash. Kinnate retains Kinnjiu’s cash, intellectual property and other assets, including key personnel and the legal entity structure. The transaction does not impact Kinnate’s cash runway, with current cash, cash equivalents and investments expected to fund current operations into mid-2024. The company also announced that KN-8701, a Phase 1 clinical trial evaluating its pan-RAF inhibitor, exarafenib, was initiated in the People's Republic of China (PRC), with trial sites now open in PRC and Taiwan."

M&A • Trial status • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Solid Tumor