“The Phase 1 clinical trial in healthy volunteers demonstrated that AVB-S6-500 was well tolerated with an acceptable safety profile. Using the pharmacodynamic data generated from this clinical trial, we have identified a dose for our upcoming Phase 1b clinical trial in platinum-resistant recurrent ovarian cancer,” said Gail McIntyre Ph.D., DABT, Senior Vice President of R&D at
The Phase 1 clinical trial was designed to assess safety, pharmacokinetics (PK) and pharmacodynamics (PD) of single ascending and repeat doses of AVB-S6-500. The clinical trial dosed 42 healthy volunteers in 5 dose cohorts. The single ascending dose portion consisted of 4 sequential dose escalation cohorts (1, 2.5, 5 and 10 mg/kg), whereas the repeat dose portion consisted of a single dose cohort (5mg/kg) receiving 4 weekly doses. Drug levels and serum GAS6 (sGAS6) levels were assessed using Aravive’s proprietary PD assay. Use of this proprietary PD assay expedited the AVB-S6-500 development program by guiding dose selection for future trials in cancer patients. This strategy minimizes administration of sub-pharmacologically active doses to cancer patients and identifies different dosing regimens to complement those of combination chemotherapy. The ability to test potential pharmacologically active doses from the start of the Phase 1b clinical trial offers the potential to assess signs of efficacy earlier in development.
There were no serious adverse events (AEs) and AVB-S6-500 was well tolerated across all doses. Serum GAS6 levels were suppressed for 22 and 29 days following single doses of 5 mg/kg and 10 mg/kg, respectively. Weekly administration of 5 mg/kg resulted in suppression of sGAS6 in 4 out of 6 subjects for at least 3 weeks after the fourth dose. Preclinical PK/PD modeling with Phase 1 healthy volunteer data and simulating increases in sGAS6 suggested that dosing regimens of 5 mg/kg every week or 10 mg/kg every other week would abrogate sGAS6 levels in cancer patients. Based on these data,
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Forward Looking Statements
This communication contains forward-looking statements (including within the meaning of Section 21E of the United States Securities Exchange Act of 1934, as amended, and Section 27A of the United States Securities Act of 1933, as amended), express or implied, concerning the Company’s goals, intentions and expectations as to future plans or events, the ability to test potential pharmacologically active doses from the start of the Phase 1b clinical trial offering the potential to assess signs of efficacy earlier in development, the expected timing of initiation of the Phase 1b portion of the Company’s Phase 1b/2 clinical trial in patients with platinum-resistant recurrent ovarian cancer, the expectation that dosing regimens of 5 mg/kg every week or 10 mg/kg every other week would abrogate sGAS6 levels in cancer patients and the plan to expand the development of AVB-S6-500 into additional tumor types. Forward-looking statements are based on current beliefs and assumptions that are subject to risks and uncertainties and are not guarantees of future performance. Actual results could differ materially from those contained in any forward-looking statement as a result of various factors, including, but not limited to, risks and uncertainties related to: the Company’s success being heavily dependent on AVB-S6-500 ; the risk that AVB-S6-500 may not have favorable results in clinical trials or receive regulatory approval; potential delays in the Company’s clinical trials due to regulatory requirements or difficulty identifying qualified investigators or enrolling patients; the risk that AVB-S6-500 may cause serious side effects or have properties that delay or prevent regulatory approval or limit its commercial potential; the risk that the Company may encounter difficulties in manufacturing AVB-S6-500; if AVB-S6-500 is approved, risks associated with its market acceptance, including pricing and reimbursement; potential difficulties enforcing the Company’s intellectual property rights; the Company’s reliance on its licensor of intellectual property and financing needs. The foregoing review of important factors that could cause actual events to differ from expectations should not be construed as exhaustive and should be read in conjunction with statements that are included herein and elsewhere, including the risk factors included in the Company’s proxy statement/prospectus/information statement filed with the
Source: Aravive, Inc.