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(State or other jurisdiction of incorporation)
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(Commission File Number)
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(IRS Employer Identification No.)
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Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)
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Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)
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Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))
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Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))
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Title of each class
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Trading
Symbol(s)
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Name of each exchange
on which registered
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Item 2.02 |
Results of Operations and Financial Condition.
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Item 8.01 |
Other Events.
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Item 9.01 |
Financial Statements and Exhibits.
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(d)
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Exhibits.
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Exhibit
No.
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Description
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Press Release dated April 17, 2023.
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Press Release dated April 17, 2023.
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104
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Cover page interactive data file (embedded within the inline XBRL document).
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KINNATE BIOPHARMA INC.
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By:
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/s/ Nima Farzan
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Nima Farzan
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President and Chief Executive Officer
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Date: April 17, 2023
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Exarafenib was well-tolerated at substantial monotherapy exposures; only 3% (n=2/60) of patients discontinued therapy due to treatment-related adverse events
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Breadth of responses observed across tumor types and BRAF or NRAS alterations with a total of 8 partial responses in the monotherapy and combination arms
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Monotherapy dose expansion ongoing at 300 mg bid; data-informed strategy prioritizes enrollment in BRAF Class II-driven melanoma and lung cancer (33% ORR);
initial data expected in the first half of 2024
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Well-tolerated monotherapy backbone enables multiple development approaches, including the ongoing exarafenib combination arm in NRAS mutant melanoma; dose
selection expected in the second half of 2023
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The maximum tolerated dose (MTD) was determined to be 300 mg bid (n=29). At therapeutically relevant exposures, there was no cutaneous (skin) evidence of paradoxical activation.
Dose limiting toxicities observed at the highest dose level (400 mg bid) were Grade 3 acneiform rash (n=1) and Grade 3 macular rash (n=1).
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Treatment-related adverse events (TRAEs) reported by investigators at any Grade occurred in 73.3% (n=44) of patients, with 18.3% of TRAEs reported as Grade 3 or higher (n=11).
There were no Grade 5 TRAEs reported as of the data cutoff.
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The most common TRAEs of any Grade were skin related (21.7%; n=13), with 3.3% (n=2) of patients having skin events that were Grade 3 or greater.
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Grade 2 gastrointestinal (GI) TRAEs occurred in 3.3% of patients (n=2). No Grade 3 GI TRAEs were observed.
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Reversible, asymptomatic increased alanine transaminase and/or increased aspartate aminotransferase TRAEs were reported at Grade 3 (n=4; 6.7%) and Grade 4 (n=1; 1.7%).
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In all patients (n=60) treated with exarafenib, the overall relative mean dose intensity was 97% and was 95% in patients treated at 300 mg bid (n=29). The median for both patient
sets was 100%.2
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Pharmacokinetic analyses demonstrated dose-dependent increases in exarafenib exposure (Cmax; peak plasma concentration and area under the curve) with increasing dose.
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Exarafenib had a half-life of eight hours in patients, which is a longer duration range than the predicted half-life preclinically, supporting a bid dosing strategy.
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At 300 mg bid, exarafenib delivered high target coverage in patients. Unbound exposures exceeded the IC50 values across BRAF and NRAS cell lines by two-to-ten-fold,
while remaining below the wild type cells IC50. We believe multiple fold target coverage is ultimately necessary for meaningful outcomes in these patient subtypes.
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Treatment with exarafenib also led to significant reductions in circulating tumor DNA across BRAF and NRAS-altered tumor types.
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In total, 6 patients achieved a partial response (PR) with exarafenib monotherapy treatment during dose escalation, including five confirmed PRs as evaluated by Response
Evaluation Criteria in Solid Tumors (RECIST). For responders, the average tumor reduction was 61% and treatment duration was 7 months. Four of the 6 responders continue exarafenib therapy.
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Treatment with exarafenib at 300 mg bid, the MTD, in patients with BRAF Class II or NRAS alterations led to a 30% (3 of 10) overall response rate (ORR).
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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.
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In addition, 71% (5 of 7) of patients with BRAF Class II alterations achieved an objective tumor reduction. In all treated patients with Class II alterations, the disease control
rate was 86% (6 of 7).
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The ORR in patients with NRAS alterations was 29% (2 of 7) at 300 mg bid and included patients with NRAS mutant melanoma and a patient with colorectal cancer harboring an NRAS
alteration co-occurring with a BRAF Class III alteration.
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The two additional subtypes with confirmed PRs included RAF inhibitor naïve patients with BRAF Class I (V600E) papillary thyroid cancer and squamous cell carcinoma. One
unconfirmed PR was reported in a RAF pretreated patient with BRAF Class I melanoma.
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Twenty-two patients achieved stable disease (SD) across dose levels, including 10 patients with objective tumor shrinkage (up to 20%), showing encouraging breadth of activity and
prolonged disease control in a broad range of alterations and tumor types.
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Enrolled 12 patients primarily with NRAS mutant melanoma into 3 combination dose cohorts: (1) exarafenib 100 mg bid and binimetinib 45 mg bid, (2) exarafenib 100 mg bid and
binimetinib 15 mg bid, and (3) exarafenib 200 mg bid and binimetinib 15 mg bid.
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Enrollment continues at exarafenib 200 mg bid dose and binimetinib 15 mg bid, with safety evaluation ongoing.
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Two of the 7 efficacy evaluable patients achieved RECIST PRs, including an unconfirmed PR in a patient with NRAS mutant melanoma and a confirmed PR in a patient with BRAF Class II
pancreatic cancer. One additional patient with NRAS mutant melanoma experienced a 25% reduction in their target lesions. Patients who responded continue combination therapy.
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Kinnate will prioritize development of the exarafenib combination in patients with NRAS mutant melanoma. The trial will also enroll RAF pre-treated patients with a BRAF Class I
alteration.
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The company expects to provide an update in the second half of 2023 on the combination dose that will be taken into dose expansion.
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KIN-7136, a next generation brain-penetrant MEK inhibitor for MAPK-driven advanced adult solid tumors, is expected to enter the clinic in
the second half of 2023
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KIN-8741, a highly selective c-MET inhibitor designed to cover acquired resistance in non-small cell lung cancer and other advanced adult
solid tumors, is expected to enter the clinic in the first half of 2024
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Kinnate to evaluate strategic alternatives for its CDK12 program
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~$231 million of cash, cash equivalents and investments as of March 31, 2023 is anticipated to fund planned operations into early 2025
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Kinnate to host virtual investor webcast today, April 17, 2023, at 5:30 pm ET
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