arav-8k_20200723.htm

 

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

 

FORM 8-K

 

CURRENT REPORT

Pursuant to Section 13 or 15(d)

of the Securities Exchange Act of 1934

Date of Report (Date of earliest event reported): July 23, 2020

 

Aravive, Inc.

(Exact name of registrant as specified in its charter)

 

 

Delaware

 

001-36361

 

26-4106690

(State or other jurisdiction

of incorporation)

 

(Commission

File Number)

 

(IRS Employer

Identification No.)

 

River Oaks Tower

3730 Kirby Drive, Suite 1200

Houston, Texas 77098

(Address of principal executive offices)

 

(936) 355-1910

(Registrant’s telephone number, including area code)

 

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions (see General Instruction A.2. below):

Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Securities registered pursuant to Section 12(b) of the Act:

 

Title of each class

 

Trading
Symbol(s)

 

Name of each exchange
on which registered

Common stock, par value $0.0001 per share

 

ARAV

 

Nasdaq Global Select Market

 

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).

Emerging growth company

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act.

 

 

 

 


 

 

Item 7.01.   Regulation FD Disclosure.

 

On July 23, 2020, Aravive, Inc. (the “Company”) issued a press release announcing the successful completion of the Phase 1b clinical trial of AVB-500 combined with standard of care therapies in patients with platinum-resistant ovarian cancer, the selection of the recommended Phase 2 dose (RP2D) and other results of the trial. A copy of the press release is furnished as Exhibit 99.1 to this Current Report on Form 8-K.

 

In addition, the Company will be making several presentations to investors over the next several weeks. In connection with the presentations, the Company intends to discuss the investor presentation, which is furnished as Exhibit 99.2 to this Current Report on Form 8-K.

The information in this Item 7.01, in the press release attached as Exhibit 99.1 and in the investor presentation attached as Exhibit 99.2 to this Current Report on Form 8-K shall not be deemed to be “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended, or otherwise subject to the liabilities of that section or Sections 11 and 12(a)(2) of the Securities Act of 1933, as amended. The information contained in this Item 7.01, in the press release attached as Exhibit 99.1 and in the investor presentation attached as Exhibit 99.2 to this Current Report on Form 8-K shall not be incorporated by reference into any filing with the U.S. Securities and Exchange Commission made by the Company, whether made before or after the date hereof, regardless of any general incorporation language in such filing.

The press release attached as Exhibit 99.1 and investor presentation attached as Exhibit 99.2 to this Current Report on Form 8-K include “safe harbor” language pursuant to the Private Securities Litigation Reform Act of 1995, as amended, indicating that certain statements contained therein are “forward-looking” rather than historical.

The Company undertakes no duty or obligation to update or revise the information contained in this Current Report on Form 8-K, although it may do so from time to time if its management believes it is appropriate. Any such updating may be made through the filing of other reports or documents with the Securities and Exchange Commission, through press releases or through other public disclosures.

Item 8.01.   Other Events. 

On July 23, 2020, the Company issued a press release announcing the successful completion of the Phase 1b clinical trial of AVB-500 combined with standard of care therapies in patients with platinum-resistant ovarian cancer, the selection of the recommended Phase 2 dose (RP2D) and other results of the trial.

The Phase1b results are set forth below:

The safety of AVB-500 has been studied in 84 subjects, including 31 healthy volunteers in a Phase 1a trial and 53 patients with PROC in a Phase 1b trial (40 in 10 mg/kg cohort, 6 in 15 mg/kg cohort, and 7 in 20 mg/kg cohort). The primary objective of the PROC trial was to assess safety of AVB-500 in combination with paclitaxel (PAC) or pegylated liposomal doxorubicin (PLD). Secondary endpoints included objective response rate (ORR), CA-125 response, clinical benefit rate, progression free survival (PFS), overall survival, pharmacokinetic (PK) profile, GAS6 serum levels, and anti-drug antibody titers.

Safety Data: Analysis of all safety data to date demonstrates that AVB-500 has been generally well-tolerated with no dose-limiting toxicities or unexpected safety signals. There have been no AVB-500-related SAEs reported to date. There were two types of adverse events that were considered related to AVB-500, as determined by an independent medical monitor: infusion reactions and fatigue. A premedication regimen was designed and implemented during the trial to manage potential infusion reactions.

Pharmacokinetics: Prior data analysis of 31 patients from the 10 mg/kg cohort showed that blood trough levels of AVB-500 demonstrated statistically significant correlation with clinical activity, as patients who achieved minimal efficacious concentration (MEC) >13.8 mg/L demonstrated a greater likelihood of response and prolonged PFS. Updated modeling using actual data from all enrolled patients demonstrated that 59%, 84%, and 93% of patients achieved MEC at doses of 10 mg/kg, 15 mg/kg, and 20 mg/kg, respectively. Furthermore, at 20 mg/kg, a large percentage of subjects is projected to have trough levels greater than 4 times the MEC. These data suggest that at 15 mg/kg, the pharmacokinetics of AVB-500 start to plateau and support the choice of 15 mg/kg as RP2D for AVB-500.

 

 


 

Preliminary Efficacy: While the Phase 1b trial was a safety trial and not powered to demonstrate efficacy, the investigator-assessed best response (RECIST V1.1) to AVB-500 across all cohorts supports promising clinical activity:

 

10 mg/kg cohort, 37 out of 40 patients evaluable:

 

31% ORR (5/16) among those treated with AVB-500 in combination with PAC, with 1 complete response (CR). Patients given AVB-500 plus PAC who achieved MEC of AVB-500 demonstrated improved ORR of 50% (4/8), with 1 CR.

 

The PFS among those who achieved MEC of AVB-500 was 7.5 months versus 2.28 months with those below MEC (p=0.0062).

 

21.6% ORR (8/37) in all evaluable patients, regardless of their MEC or use of PAC or PLD.

 

All responses have been confirmed.

 

15 mg/kg cohort, 5 out of 6 patients evaluable:

 

 

All 5 patients in this cohort experienced clinical benefit, with 1 CR (continuing to show CR 3 months after discontinuing chemotherapy while on AVB-500 as single agent), 2 partial responses (PR), and 2 stable disease (SD).

 

All responses have been confirmed.

 

20 mg/kg cohort, 7 out of 7 patients evaluable:

 

 

Of the 7 patients in this cohort, there was 1 PR (with CR of target lesion; not confirmed), 1 SD, and 5 with progressive disease (PD).

 

A post-hoc analysis of tumor expression showed that 4 patients whose best response was PD did not express GAS6 (3) and/or had low amounts of AXL (2) on immunohistopathology of their tumors. While they were enrolled per protocol in the Phase 1b trial, these patients do not appear to be representative of the eventual AVB-500 target population, as they are mostly rare subtypes of PROC and such patients based on their clinical characteristics will not be eligible for the planned Phase 2/3 trial.

 

Other notable findings:

 

AVB-500 plus PAC appeared to perform better than AVB-500 plus PLD.

 

o

Across all cohorts, AVB-500 plus PAC data show an ORR of 35% (8/23, including 2 CRs) compared to ORR of 15% (4/26) in AVB-500 plus PLD.

 

 

AVB-500 plus chemo appeared to perform better in patients without previous exposure to bevacizumab.

 

o

In a subgroup analysis of patients who had not been previously exposed to bevacizumab in their prior lines of therapy, AVB-500 yielded an ORR of 60% (6/10 including 2 CR) when combined with PAC and an ORR of 19% (3/16) when combined with PLD. For reference, control arms of the third-party AURELIA Trial of bevacizumab (NCT00976911) showed ORR of 30.2% (out of 55 patients total) with PAC alone and 7.8% (out of 64 patients total) with PLD alone.

 

 

Serum levels of soluble AXL (sAXL)/GAS6 ratio seemed to correlate with response to AVB-500.

 

o

In the entire Phase 1b cohort, patients with a high sAXL/GAS6 ratio had 30% ORR (10/33) versus 0% ORR (0/15) in patients with a low sAXL/GAS6 ratio. In the PAC cohort, patients with a high sAXL/GAS6 ratio had 43% ORR (6/14) versus 0% ORR (0/7) in patients with a low sAXL/GAS6 ratio. Notably, patients with high sAXL/GAS6 ratio who had not previously received bevacizumab achieved ORR of 71% (5/7).

 

o

Historically, high sAXL has been associated with a poor prognosis; however, AVB-500 plus PAC or PLD appeared correlated with improved clinical outcomes in this population.

 

o

Use of serum biomarkers such as sAXL/GAS6 ratio as potential stratification biomarker(s) will be explored in future clinical trials.

 

 

 


 

 

While not powered to demonstrate efficacy, drug exposure levels correlated with clinical response, supporting the use of higher dose of AVB-500. AVB-500 combined with PAC had better clinical responses in patients whose trough levels were above the minimal efficacious concentration (MEC) of 13.8mg/L compared to those patients whose trough levels were below the MEC.

 

 

AVB-500 performed well in late line therapy and showed improved clinical benefit in patients who were on their third and fourth lines of therapy or who progressed in less than 3 months following their last platinum-containing regimen.

 

The Company also announced its decision to terminate the Phase 2a clinical trial of AVB-500 in patients with kidney fibrosis, specifically IgA Nephropathy (IgAN) (NCT04042623) in order to primarily focus on patients with cancer.

 

Item 9.01.   Financial Statements and Exhibits.

(d) Exhibits.

The following exhibits are filed with this Current Report on Form 8-K:

 

Exhibit

Number

 

Description

 

 

 

99.1

  

Press Release issued by Aravive, Inc. dated July 23, 2020

99.2

  

Investor Presentation of Aravive, Inc

 

 


 

 


 

SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, as amended, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

 

Date: July 23, 2020

ARAVIVE, INC.

(Registrant)

 

 

 

By:

 

/s/ Vinay Shah

 

Name:

 

Vinay Shah

 

Title:

 

Chief Financial Officer

 

 

 

 

 

 

 

 

arav-ex991_6.htm

Exhibit 99.1

 

Aravive Announces Successful Completion of Phase 1b Trial Evaluating AVB-500

in Platinum Resistant Ovarian Cancer

 

Identifies Recommended Phase 2 Dose for Continued Clinical Development of AVB-500

in Platinum Resistant Ovarian Cancer

 

Aravive to Host Conference Call and Webcast Today at 8:30 a.m. ET

 

HOUSTON, July 23, 2020 – Aravive, Inc. (Nasdaq: ARAV), a clinical-stage oncology company developing transformative therapeutics, today announced the successful completion of the Phase 1b trial of its AVB-500 drug candidate in platinum resistant ovarian cancer (PROC) and selection of the recommended Phase 2 dose (RP2D).

 

“Aravive is grateful to the patients and their physicians who participated in this trial,” said Gail McIntyre, Ph.D., chief executive officer at Aravive. “We are very encouraged by the potential of AVB-500 to improve responses and progression free survival in combination with chemotherapy in platinum resistant ovarian cancer. The information we have obtained from the clinical data together with some informal preliminary feedback from the FDA have helped inform our Phase 2/3 trial strategy. We look forward to formally discussing these results and our development plan with the FDA by the end of 2020.”

 

Phase 1b Results

The safety of AVB-500 has been studied in 84 subjects, including 31 healthy volunteers in a Phase 1a trial and 53 patients with PROC in a Phase 1b trial (40 in 10 mg/kg cohort, 6 in 15 mg/kg cohort, and 7 in 20 mg/kg cohort). The primary objective of the PROC trial was to assess safety of AVB-500 in combination with paclitaxel (PAC) or pegylated liposomal doxorubicin (PLD). Secondary endpoints included objective response rate (ORR), CA-125 response, clinical benefit rate, progression free survival (PFS), overall survival, pharmacokinetic (PK) profile, GAS6 serum levels, and anti-drug antibody titers.

 

Safety Data: Analysis of all safety data to date demonstrates that AVB-500 has been generally well-tolerated with no dose-limiting toxicities or unexpected safety signals. There have been no AVB-500-related SAEs reported to date. There were two types of adverse events that were considered related to AVB-500, as determined by an independent medical monitor: infusion reactions and fatigue. A premedication regimen was designed and implemented during the trial to manage potential infusion reactions.

 

Pharmacokinetics: Prior data analysis of 31 patients from the 10 mg/kg cohort showed that blood trough levels of AVB-500 demonstrated statistically significant correlation with clinical activity, as patients who achieved minimal efficacious concentration (MEC) >13.8 mg/L demonstrated a greater likelihood of response and prolonged PFS. Updated modeling using actual data from all enrolled patients demonstrated that 59%, 84%, and 93% of patients achieved MEC at doses of 10 mg/kg, 15 mg/kg, and 20 mg/kg, respectively. Furthermore, at 20 mg/kg, a large percentage of subjects is projected to have trough levels greater than 4 times the MEC. These data suggest that at 15 mg/kg, the pharmacokinetics of AVB-500 start to plateau and support the choice of 15 mg/kg as RP2D for AVB-500.

 

Preliminary Efficacy: While the Phase 1b trial was a safety trial and not powered to demonstrate efficacy, the investigator-assessed best response (RECIST V1.1) to AVB-500 across all cohorts supports promising clinical activity:

 

10 mg/kg cohort, 37 out of 40 patients evaluable:

 

31% ORR (5/16) among those treated with AVB-500 in combination with PAC, with 1 complete response (CR). Patients given AVB-500 plus PAC who achieved MEC of AVB-500 demonstrated improved ORR of 50% (4/8), with 1 CR.

 

The PFS among those who achieved MEC of AVB-500 was 7.5 months versus 2.28 months with those below MEC (p=0.0062).

 

21.6% ORR (8/37) in all evaluable patients, regardless of their MEC or use of PAC or PLD.

 


 

 

All responses have been confirmed.

 

15 mg/kg cohort, 5 out of 6 patients evaluable:

 

All 5 patients in this cohort experienced clinical benefit, with 1 CR (continuing to show CR 3 months after discontinuing chemotherapy while on AVB-500 as single agent), 2 partial responses (PR), and 2 stable disease (SD).

 

All responses have been confirmed.

20 mg/kg cohort, 7 out of 7 patients evaluable:

 

Of the 7 patients in this cohort, there was 1 PR (with CR of target lesion; not confirmed), 1 SD, and 5 with progressive disease (PD).

 

A post-hoc analysis of tumor expression showed that 4 patients whose best response was PD did not express GAS6 (3) and/or had low amounts of AXL (2) on immunohistopathology of their tumors. While they were enrolled per protocol in the Phase 1b trial, these patients do not appear to be representative of the eventual AVB-500 target population, as they are mostly rare subtypes of PROC and such patients based on their clinical characteristics will not be eligible for the planned Phase 2/3 trial.

Other notable findings:

 

AVB-500 plus PAC appeared to perform better than AVB-500 plus PLD.

 

o

Across all cohorts, AVB-500 plus PAC data show an ORR of 35% (8/23, including 2 CRs) compared to ORR of 15% (4/26) in AVB-500 plus PLD.

 

 

AVB-500 plus chemo appeared to perform better in patients without previous exposure to bevacizumab.

 

o

In a subgroup analysis of patients who had not been previously exposed to bevacizumab in their prior lines of therapy, AVB-500 yielded an ORR of 60% (6/10 including 2 CR) when combined with PAC and an ORR of 19% (3/16) when combined with PLD. For reference, control arms of the third-party AURELIA Trial of bevacizumab (NCT00976911) showed ORR of 30.2% (out of 55 patients total) with PAC alone and 7.8% (out of 64 patients total) with PLD alone.

 

 

Serum levels of soluble AXL (sAXL)/GAS6 ratio seemed to correlate with response to AVB-500.

 

o

In the entire Phase 1b cohort, patients with a high sAXL/GAS6 ratio had 30% ORR (10/33) versus 0% ORR (0/15) in patients with a low sAXL/GAS6 ratio. In the PAC cohort, patients with a high sAXL/GAS6 ratio had 43% ORR (6/14) versus 0% ORR (0/7) in patients with a low sAXL/GAS6 ratio. Notably, patients with high sAXL/GAS6 ratio who had not previously received bevacizumab achieved ORR of 71% (5/7).

 

o

Historically, high sAXL has been associated with a poor prognosis; however, AVB-500 plus PAC or PLD appeared correlated with improved clinical outcomes in this population.

 

o

Use of serum biomarkers such as sAXL/GAS6 ratio as potential stratification biomarker(s) will be explored in future clinical trials.

“Improved therapeutic approaches, especially targeted therapies, are urgently needed for patients with ovarian cancer who are resistant to standard of care therapy and have limited treatment options,” said Katherine Fuh, M.D., Ph.D., Assistant Professor, Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Center for Reproductive Health Sciences, Washington University School of Medicine, St. Louis, MO. “AVB-500’s novel mechanism of action has the potential to be combined with any number of anticancer agents, including DNA-damaging agents, PARP inhibitors, bevacizumab as well as immuno-oncology agents and check point inhibitors to change the way we treat ovarian cancer.”

 

Conference Call Information

Aravive will host a live conference call and webcast at 8:30 a.m. ET today to discuss these clinical data. The conference call may be accessed by dialing (844) 281-9845 (domestic) and (314) 888-4254 (international) and referring to conference ID 6277266. A webcast of the conference call and an accompanying slide presentation will be available in the Investors

 


 

section of the Aravive website at https://ir.aravive.com. The archived webcast will be available on Aravive’s website after the conference call.

 

About AVB500-OC-002

Aravive initiated a Phase 1b dose-escalation trial (AVB500-OC-002) evaluating AVB-500 in combination with pegylated liposomal doxorubicin (PLD) or paclitaxel (PAC) for patients with platinum resistant ovarian cancer (PROC) in December 2018. Aravive reported positive preliminary data from the Phase 1b trial at 10 mg/kg in November 2019, demonstrating a relationship between AVB-500 blood levels and anti-tumor response. Additionally, AVB-500 is being studied in Investigator-sponsored Phase 1/2 trials, in combination with durvalumab in patients with platinum-resistant recurrent epithelial ovarian cancer and with avelumab in patients with advanced urothelial Carcinoma (COAXIN).

 

About AVB-500
AVB-500 is a therapeutic recombinant fusion protein that has been shown to neutralize GAS6 activity by binding to GAS6 with very high affinity in preclinical models. In doing so, AVB-500 selectively inhibits the GAS6-AXL signaling pathway which is upregulated in multiple cancer types including ovarian cancer. In preclinical studies, GAS6-AXL inhibition has shown anti-tumor activity in combination with a variety of anticancer therapies including radiation therapy, immuno-oncology agents, and chemotherapeutic drugs that affect DNA replication and repair. Increased expression of AXL and GAS6 in tumors has been correlated with poor prognosis and decreased survival and has been implicated in therapeutic resistance to conventional chemotherapeutics and targeted therapies. AVB-500 is currently being evaluated in clinical trials and has been
granted Fast Track Designation by The U.S. Food and Drug Administration (FDA) in platinum-resistant recurrent ovarian cancer.

 

About Aravive
Aravive, Inc. (Nasdaq: ARAV) is a clinical-stage oncology company developing transformative treatments designed to halt the progression of life-threatening diseases. Aravive’s lead product candidate, AVB-500, is an ultra-high affinity decoy protein that targets the GAS6-AXL signaling pathway. Aravive recently initiated a discovery program to develop a high affinity bispecific program targeting CCN2 (CTGF) for treatment of cancer and fibrosis. For more information, please visit 
www.aravive.com.

 

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, such as the potential of AVB-500 to improve responses and progression free survival in combination with chemotherapy in platinum resistant ovarian cancer, the potential of a Phase 2/3 trial, and the potential of combining AVB-500’s novel mechanism of action with other anticancer agents, including DNA-damaging agents, PARP inhibitors, bevacizumab as well as immuno-oncology agents and check point inhibitors to change the way we treat ovarian cancer. Forward-looking statements are based on current beliefs and assumptions, are not guarantees of future performance and are subject to risks and uncertainties that could cause actual results to 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 ability to show the potential of AVB-500 to improve responses and progression free survival in combination with chemotherapy in platinum resistant ovarian cancer, the Company’s ability to successfully combine AVB-500’s novel mechanism of action with other anticancer agents, the ability to properly fund the Company, the ability of the new directors and management team to deliver on the Company's strategic vision and execute on its business plan, the impact of COVID-19 on the Company's clinical strategy, clinical trials, supply chain and fundraising, the Company's ability to expand development into additional oncology and fibrotic indications, the Company's dependence upon AVB-500, AVB-500's ability to have favorable results in clinical trials, the clinical trials of AVB-500 having results that are as favorable as those of preclinical and clinical trials, the ability to receive regulatory approval, potential delays in the Company's clinical trials due to regulatory requirements or difficulty identifying qualified investigators or enrolling patients especially in light of the COVID-19 pandemic; the risk that AVB-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-500; if AVB-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 Annual Report on Form 10-K for the fiscal year ended December 31, 2019, recent Current Reports on Form 8-K and subsequent filings with the SEC. Except as required by applicable law, the Company undertakes no obligation to revise or update any forward-looking statement, or to make any other forward-looking statements, whether as a result of new information, future events or otherwise.

# # #

 

Contacts:
Media:

Sheryl Seapy, W2O

sseapy@w2ogroup.com

(949) 903-4750

 

Investors:
Luke Heagle, W2O  

lheagle@w2ogroup.com

(910) 726-1372


arav-ex992_361.pptx.htm

Slide 1

© 2020 Aravive, Inc. Corporate Presentation July 2020 Halting Disease Progression in its Tracks Exhibit 99.2

Slide 2

© 2020 Aravive, Inc. Forward-Looking Statements This presentation contains forward-looking statements that may discuss Aravive’s plans, goals, intentions and expectations as to future trends, events, results of operations, financial condition or other matters. Forward- looking statements generally include statements that are predictive in nature and depend upon or refer to future events or conditions, and they often include words such as “may,” “will,” “should,” “would,” “expect,” “anticipate,” “plan,” “likely,” “believe,” “estimate,” “project,” “intend,” and other similar expressions. Statements that are not historical facts are forward-looking statements. Forward-looking statements included in this presentation include statements regarding Aravive’s planned clinical activities, including the design, initiation, patient enrollment and availability of data from clinical studies, potential pipeline, future indications and cash position and the anticipated safety, activity and manufacturability of Aravive’s product candidates. Forward-looking statements are based on Aravive’s current beliefs and assumptions, 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, without limitation: the unpredictability of clinical development activities; the impact of the COVID-19 pandemic; risks related to Aravive’s ability to estimate and control its operating expenses; Aravive’s ability to protect its intellectual property rights; changes in the competitive environment; and legislative, regulatory, political and economic developments. 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 Aravive’s most recent Annual Report on Form 10-K, Quarterly Report on Form 10-Q and Current Reports on Form 8-K filed with the Securities and Exchange Commission. Except as required by law, Aravive undertakes no obligation to revise or update any forward-looking statement or to make any other forward-looking statements, whether as a result of new information, future events or otherwise.

Slide 3

© 2020 Aravive, Inc. Aravive is a clinical stage company developing treatments designed to halt the progression of life-threatening diseases, including cancer and fibrosis. Nasdaq-listed company (ARAV) Offices in Houston, TX (HQ) and RTP, NC $20 million Product Development Award from the Cancer Prevention & Research Institute of Texas (CPRIT) Led by a team of industry veterans with decades of target biology, drug development & commercialization expertise Multiple milestones anticipated during 2020 & 2021 Lead Clinical program is GAS6/AXL inhibitor and preclinical program in CTGF, both important targets in cancer and fibrosis Company Overview Our approach draws on novel insights into targeting signaling pathways that drive the activation, migration, and invasion of abnormal cells into healthy tissues.

Slide 4

© 2020 Aravive, Inc. A first-in-class, ultra-high affinity, Fc-fusion protein designed to selectively block the novel GAS6-AXL signaling pathway Proof-of-mechanism established in clinic using proprietary biomarker for target engagement Early proof-of-concept for anti-tumor activity demonstrated in platinum-resistant ovarian cancer (PROC) Fast-track designation granted by the FDA Completed Phase 1b and plan to initiate P2/3 trial for platinum-resistant ovarian cancer 2H20/Q121 following discussion with the FDA Ideal profile for combination with chemotherapy, checkpoint inhibitors and PARP inhibitors in broad range of indications IP coverage through 2033 and beyond AVB-500: Lead Clinical Program

Slide 5

© 2020 Aravive, Inc. Indication Preclinical 3rd Oncology (undisclosed indication) Status: IND Open Status: Recruiting Status: Recruiting Phase 1 Phase 3 Phase 2 Phase 2a Phase 2b Anti-CTGF AVB-500 IST with AstraZeneca Ovarian Cancer platinum resistant (PAC or PLD combination) Ovarian Cancer platinum resistant (PDL1i combination) Clear Cell Renal Cancer 2L (cabozantinib combination) Advanced Urothelial Cancer (PDL1 Combination) Cancer and Fibrosis WuXi Biologics Collaboration Status: P1b complete; plan to initiate Phase 2/3 trial in 2H20/Q121 Status: Recruiting Status: Plan to initiate @ 15 mg/kg Status: Recruiting IST with EMD Serono * Phase 1 for AVB-500 was conducted in healthy volunteers, allowing any next AVB-500 study to be either Phase 1b or Phase 2 study IST= investigator sponsored trial Pipeline Focused on GAS6/AXL Signaling in Oncology Phase 1* Phase 1b

Slide 6

AXL is a member of tyrosine kinases that include Tyro3, AXL, and Mer (TAMs) AXL is activated by a single ligand, growth arrest– specific 6 (GAS6); Mer and Tyro3 can be activated by GAS6 and Protein S 1 Upregulated in many cancers 2, AXL overexpression linked to metastasis 3 ,4, poor survival 5-7, and drug resistance 8 9 Unusually strong binding affinity between GAS6 and AXL of ~ 30 pM makes development of inhibitors to the pathway challenging 1 Combo with ChemoTx 1 J Clin Invest. 2017;127(1):183–198. 2 Adv Cancer Res. 2008;100:35–83. 3 Oncogene. 2009;28(39):3442–3455 4 Cancer Res. 2010;70(19):7570–7579 5 Proc Natl Acad Sci U S A. 2006;103(15):5799–5804 6 Ann Diagn Pathol. 2013;17(5):425–429 7 Proc Natl Acad Sci U S A. 2010;107(3):1124–1129 8 Nat Genet. 2012;44(8):852–860 9 Cancer Res. 2013;73(1):331–340 GAS6/AXL Pathway is Critical in Cancer Biology and Promotes Invasion, Metastasis and Resistance Invasive Cancers like PROC, RCC Leukemia Combo with IO’s Combo DDR’s, PARPi VEGFi & TKI’s © 2020 Aravive, Inc.

Slide 7

© 2020 Aravive, Inc. AVB-500 Decoy has fM Affinity to neutralize GAS6 Selectivity limited by RTK homology Off-target toxicity Multiple resistance mechanisms Many potential competitors Requires a mAB affinity that competes with receptor Not achievable for AXL Many potential competitors Binds more tightly to GAS6 than WT AXL Complete target coverage with no anticipated off-target toxicity First-in-class with strong IP position kinase domain Tyrosine Kinase Inhibitor Engineered Decoy Receptor is the Best Approach for Potent and Selective Inhibition of GAS6/AXL Signaling Decoy AXL Receptor AXL or GAS6 Antibody

Slide 8

© 2020 Aravive, Inc. DRUG (STAGE) COMPANY TARGET SELECTIVE FOR AXL AVB-500 (Ph Ib/II) Aravive GAS6 YES gilteritinib (Market; AML) Astellas AXL (Multi-kinase) NO cabozantinib (Market; RCC & HCC) Exelixis AXL (Multi-kinase) NO sitravatinib (Ph III) Mirati (BeiGene) AXL (Multi-kinase) NO merestinib (Ph II) Lilly AXL (Multi-kinase) NO bemcentinib (Ph II) BerGenBio AXL (Multi-kinase) NO TP-0903 (Ph I/II) Tolero (Sumitomo) AXL (Multi-kinase) NO BPI-9016M (Ph I) Betta Pharmaceuticals AXL (Multi-kinase) NO ONO-7475-01 (Ph I) Ono Pharmaceuticals AXL (Multi-kinase) NO RXDX-106 (Ph I) Ignyta AXL (Multi-kinase) NO VS Other Drugs Targeting AXL Signaling in Clinical Development are Not Selective

Slide 9

© 2020 Aravive, Inc. AVB-500 (AVB): q14 days Pegylated liposomal doxorubicin (PLD) 40 mg/m2 d1 28-day cycle paclitaxel (PAC): 80 mg/m2 day 1, day 8, day 15; Maintenance dosing on AVB-500 monotherapy AVB 500 10 mg/kg + PLD AVB 500 15 mg/kg + PLD Select RP2D AVB 500 10 mg/kg + PAC AVB 500 15 mg/kg + PAC PLATINUM-RESISTANT OVARIAN CANCER AVB 500 20 mg/kg + PLD AVB 500 20 mg/kg + PAC Key Eligibility Criteria 1-3 prior lines of therapy, not including maintenance or adjuvant therapy Measurable disease Platinum free interval ≤ 6mo after most recent platinum-containing regimen Adults with adenocarcinoma NOS, high grade endometrioid adenocarcinoma, mixed epithelial (≥ 80% high grade serous), high grade serous, or undifferentiated carcinoma ECOG performance status 0-1 iDMC= Independent Data Monitoring Committee NOS= Not Otherwise Specified ECOG= Eastern Cooperative Oncology Group IDMC Review IDMC Review Phase 1b Study of AVB-500 in Platinum-Resistant Ovarian Cancer (NCT03639246)

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Overall Phase 1b Baseline Characteristics and Demographics  10 MG/KG PER PROTOCOL COHORT AVB+PAC AVB+PLD OVERALL AGE, YEARS n 23 30 53 Mean 63.95 64.32 64.16 HISTOLOGY AT DIAGNOSIS Adenocarcinoma NOS 2 (8.7%) 1 (3%) 3 (5.7%) High-grade Endometroid Adenocarcinoma 1 (4.3%) 1 (3%) 2 (3.7%) High-grade Serous Adenocarcinoma 19 (82.6%) 28 (93%) 47 (88.7%) Mixed Epithelial Carcinoma 0 0 0 Undifferentiated Carcinoma 1 (4.3%) 0 1 (1.9%) PRIOR LINES 1 1 (4.3%) 17 (56.7%) 18 (34%) 2 13 (56.5%) 10 (30%) 23 (43.4%) 3 9 (39.1%) 3 (10%) 12 (22.6%) PLATINUM-FREE INTERVAL (PFI) < 3 months 10 (43.5%) 7 (23.3%) 17 (32.1%) >= 3 months 13 (56.5%) 23 (76.7%) 36 (67.9%) ECOG PERFORMANCE STATUS 0 14 (60.9%) 16 (53.3%) 30 (56.6%) 1 9 (39.1%) 14 (46.7%) 23 (43.4%) More heavily pretreated patients tend to receive paclitaxel © 2020 Aravive, Inc.

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Safety report for trial AVB500-OC-002 generated by independent medical monitor concluded: “Based on a review of the safety data, no unexpected safety trends have been detected and the reported AE severity and frequency are consistent with expectations of the concomitant treatment (PAC or PLD) and the disease under study (ovarian cancer).” AVB-500 well-tolerated: fatigue and infusion reactions appeared to be related to treatment No serious events that required expedited reporting per Sponsor No drug related SAEs reported to date No dose-limiting toxicities Premedication regimen designed to manage potential infusion reactions employed during the trial 53 PROC Patients Dosed: 10 mg/kg (40); 15 mg/kg (6); and 20 mg/kg (7) Safety Data Summary from Phase 1b Study © 2020 Aravive, Inc.

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Trough levels statistically significantly correlate with response and prolonged PFS Updated modeling with actual PK data shows 59%, 84% and 93% of patients are expected to achieve minimal efficacious concentration (MEC) at 10 mg/kg, 15 mg/kg, 20 mg/kg, respectively PK appears to plateau at 15 mg/kg At 20 mg/kg, a large proportion of patients are projected to have trough level greater than 4 times the threshold 10 mg/kg 15 mg/kg 20 mg/kg Predicted --- MEC of 13.8mg/L AVB-500 Phase 1b Study: RP2D is 15 mg/kg Data support 15 mg/kg as RP2D for PROC © 2020 Aravive, Inc. RP2D= Recommended Phase 2 Dose

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INVESTIGATOR-ASSESSED BEST RESPONSE PER RECIST V1.1 PAC (N=23) PLD (N=26) CR 2 (8.7%) 0 PR 6 (26%) 4 (15%) ORR 8 (35%) 4 (15%) SD 6 (26%) 12 (46%) CBR 14 (61%) 16 (61.5%) PD 9 (39%) 10 (38.5%) 1 A. Davis et al. / Gynecologic Oncology 133 (2014) 624–631 Response Higher in PAC than Historical Data of 10-15%1 Summary of all Cohorts, Evaluable Per Protocol All responses confirmed except the one PAC patient at 20 mg/kg ORR across all dose cohorts of 12/49 patients (24%) © 2020 Aravive, Inc.

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CLINICAL RESPONSE OF AVB-500+CHEMO IN 3L AND 4L CLINICAL RESPONSE OF CHEMOTHERAPY IN 3L AND 4L PER BRUCHIM ET AL, 2013 (N=99) 34 patients in AVB-500+chemo group overall; 20 patients in the high exposure AVB-500+chemo group; Two CRs in High Exposure Category Updated analysis based on all per protocol patients ORR= objective response rate; SD=stable disease; CBR=clinical benefit rate; PD=progressive disease; Historical data from European Journal of Obstetrics & Gynecology and Reproductive Biology 166 (2013) 94–98; 3L included (in order of use) taxol, carboplatin, topotecan, etoposide, gemzar, doxil, tamoxifen, adriamycin, carbo+taxol, and "other“; 4L was predominantly taxol. AVB-500 + Chemo Showed Improved Clinical Benefit in Patient Subsets that Generally Respond Poorly to Chemo (Later Lines of Therapy)

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Updated analysis based on all per protocol patients CLINICAL RESPONSE OF CHEMOTHERAPY IN PATIENTS WITH <3MO PFI PER KOBAYASHI-KATO ET AL, 2019 (N=21) CLINICAL RESPONSE OF AVB-500+CHEMO IN PATIENTS WITH <3MO PFI ORR= objective response rate; SD=stable disease; CBR=clinical benefit rate; PD=progressive disease; PFI=platinum-free interval 16 patients in AVB-500 +chemo group overall, 12 patients in the high exposure AVB-500 +chemo group; Two responders in chemo + AVB-500 high exposure group had CR. Historical data from Cancer Chemotherapy and Pharmacology (2019) 84:33-39 37; included PLD; GEM; CPT-11 (irinotecan); topotecan; and paclitaxel; no CRs in historical data (1 PR in historical data) AVB-500 + Chemo Showed Improved Clinical Benefit in Patient Subsets that Generally Respond Poorly to Chemo (PFI < 3 months)

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10 mg/kg cohort, 37 out of 40 patients evaluable: 31% ORR (5/16) in combination with PAC, 1 complete response (CR) 50% ORR (4/8), with 1 CR in PAC patients achieving MEC of AVB-500 mPFS 7.5 months versus 2.28 months for those achieving MEC vs. those below MEC (p=0.0062) 21.6% ORR (8/37) in all evaluable patients, regardless of their MEC or use of PAC or PLD All responses have been confirmed  15 mg/kg cohort, 5 out of 6 patients evaluable: 5/5 demonstrated clinical benefit, 1 CR (continuing to show CR 3 months while on AVB-500 alone), 2 PR, and 2 SD All responses have been confirmed 20 mg/kg cohort, 7 out of 7 patients evaluable: 1 PR (with CR of target lesion; not confirmed), 1 SD, and 5 with PD Post-hoc analysis of tumor expression showed that 4 patients whose best response was PD did not express GAS6 (3) and/or had low amounts of AXL (2) on immunohistopathology of their tumors While enrolled per protocol, these patients are not representative of the eventual AVB-500 target population as they have rare subtypes of PROC; based on their clinical characteristics, such patients will not be eligible for the planned Phase 2/3 trial MEC= minimal efficacious concentration mPFS= median progression-free survival ORR= overall response rate CR= complete response; SD= stable disease; PD= progressive disease Summary of AVB-500 Cohort Data © 2020 Aravive, Inc.

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AVB-500 has better activity in: Combination with PAC Patients whose C1D15 trough level >13.8mg/L Patients who have not previously been treated with bevacizumab Patients with high baseline sAXL/GAS6 ALL INDEPENDENT OF EACH OTHER Phase 1b Findings Aid Phase 2/3 Trial Design © 2020 Aravive, Inc.

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  AVB500 + PACLITAXEL ABOVE MEC BELOW MEC Number of Patients (n) 14 9 Complete Response (CR) 2 (14%) 0 Partial Response (PR) 4 (28%) 2 (22%) Overall Response Rate (ORR) 6 (43%) 2 (22%) Stable Disease (SD) 3 (21%) 3 (33%) Clinical Benefit (SD+ORR) 9 (64%) 5 (55%) Progressive Disease (PD) 5 (36%) 4 (45%) Median Duration of Response (months) 7.21 1.5, 3.7* Unsupervised analysis identified AVB-500 trough levels as being statistically significantly associated with progression free survival (PFS) Minimal efficacious concentration (MEC) determined via AIC analysis to be 13.8mg/L CBR in PLD Above MEC group 76% vs 33% in Below MEC AIC = Akaike Information Criterion All responses confirmed except the one PAC patient at 20mg/kg * Actual values displayed because there are only 2 responders AVB-500 Combined with Paclitaxel Demonstrated Better Clinical Responses in High Drug Exposure Group © 2020 Aravive, Inc.

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Blue = above 13.8 mg/L Red = below 13.8 mg/L AVB-500+ PAC AVB-500+ PAC or PLD Significant Improvement of mPFS in Patients with High Drug Exposure More Pronounced in 10mg/kg AVB-500 +PAC vs. PLD © 2020 Aravive, Inc.

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49 pts in per protocol population, no quantitative CT data for 08-0001 (patient shown on x-axis all the way to right in figure); 4 pts with target lesions that were stable were determined to be PD as best response 10 mg/kg 15 mg/kg 20 mg/kg Target lesions in ~70% patients were stable (i.e, w/in +20 to -30% ) or decreased (≥ -30% ) from baseline % Change in Target Lesions at Best Response by AVB Dose Level © 2020 Aravive, Inc.

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Days 50 100 150 200 250 300 350 * * * # # Trough above MEC Trough below MEC Per protocol population * Still on study # on AVB-500 alone after 6 mos chemo # Duration of Treatment by Trough above MEC: Patients with Higher Exposures Stayed on Treatment Longer © 2020 Aravive, Inc.

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AVB-500 + PAC PRIOR BEVACIZUMAB No Yes N 10 13 CR 2 (20%) 0 PR 4 (40%) 2 (15%) ORR 6 (60%) 2 (15%) SD 1 (10%) 5 (38%) CBR 7 (70%) 7 (54%) PD 3 (30%) 6 (46%) 1 Journal of Clinical Oncology, Vol 33, No 32 (November 10), 2015: pp 3836-383 Third-Party Historical Data as Benchmark (AURELIA Study1) Subgroup analysis of the control arms in the AURELIA (NCT00976911) bevacizumab study has shown: ORR of 30.2% with PAC alone (AVB-500 + PAC à 60%) PFS of 3.9 mo. with PAC alone (AVB-500 + PAC à 7.4 mo.) ORR of 7.8% with PLD alone (AVB-500 + PLD à 19%) Of note, the benefit observed with AVB-500 + PAC was among patients with worse prognostic factors than observed in AURELIA. Compared to the historical benchmark set by AURELIA, Aravive study had greater proportion of patients with: Larger baseline target lesions (target lesion >1 cm 75% vs. 100%, because approximately 25% of AURELIA population had no detectable lesion at enrollment) More patients falling in the PFI category of less than 3 months (43% vs. 27%), More patients with >2 prior lines of chemotherapy (39% vs. 0%) The historical 3rd-party data are for illustrative purposes only; the Aravive P1b trial was not powered to demonstrate efficacy. Clinical Activity of AVB-500 + PAC was More Pronounced in Patients not Previously Treated with Bevacizumab © 2020 Aravive, Inc.

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sAXL/GAS6 >0.773 Yes NO N 14 7 CR 2 (14%) 0 PR 4 (28%) 0 ORR 6 (43%) 0 SD 2 (14%) 4 (57%) CBR 8 (57%) 4 (57%) PD 6 (43%) 3 (43%) sAXL not available for 2 patients Similar results seen in PLD combination Serum levels of sAXL/GAS6 ratio in a post-hoc analysis correlated with response to AVB-500 + chemo, and will be further explored in future studies 30% (10/33) vs. 0% (0/15) ORR in patients with a high sAXL/GAS6 ratio vs low (In the entire Ph1b cohort) 43% (6/14) vs. 0% (0/7) ORR in patients with a high sAXL/GAS6 ratio vs low (PAC cohort) 71% (5/7) ORR in patients high sAXL/GAS6 ratio with no prior Bevacizumab use (PAC cohort) Historically, high sAXL is associated with poor prognosis; however, AVB-500 plus chemo appears to improve clinical outcome in this population. Potential Biomarker: Baseline Serum sAXL/GAS6 AVB-500 Demonstrated Higher Response in PAC + AVB-500 Patients with Higher sAXL/GAS6 © 2020 Aravive, Inc.

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Potential Registrational Study Primary objective to assess anti-tumor activity of AVB-500 in combination with PAC as measured by PFS FDA’s preliminary feedback Current RCT design is expected to be appropriate Investigating adaptive designs / interim analyses exploring potential biomarkers or alternative end points Anticipate FDA meeting by end of 2020 Anticipate initiating 2H20/Q121, subject to the impact of COVID-19 Exploratory Biomarkers: serum GAS6, AVB-500 drug levels, serum sAXL/GAS6 ratio © 2020 Aravive, Inc. Randomized, Double-Blind, Placebo-Controlled Trial to Compare Efficacy and Tolerability of AVB-500 + PAC versus PAC Planned Phase 2/3 Trial AVB-500 + PAC Placebo + PAC Platinum-Resistant Ovarian Cancer 1-3 prior lines Measurable disease

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2Q 2019 – POM in Ovarian Cancer 2Q 2019 – Tolerability in Ovarian Cancer 3Q 2019 – Early POC in Ovarian Cancer 3Q 2019 – Expanded P1b Ovarian Cancer 4Q 2019 – IgAN Initiated* 1Q 2020 – IND open for ccRCC study Mid-2020 – Safety and PK from Ph1b PROC 2H 2020/Q1 2021 – P2/P3 PROC initiation 2H 2020 – P1b/P2 ccRCC initiation at 15 mg/kg Note: Above milestones may be impacted by COVID-19 2019 Achieved Milestones IND= investigational new drug application; POM= proof of mechanism; POC= proof of concept *2Q 2020 study halted because of COVID-19 and, in 3Q 2020, decided to terminate study to focus on oncology Experienced, Methodical, Efficient Development Execution Strong Clinical Development Team 2020 Milestones © 2020 Aravive, Inc.

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Expand Board of Directors Opportunistic with respect to business development deals around our pipeline ex-U.S. Focus on oncology: Advance PROC Phase 2/3 trial Initiate ccRCC trial Potential pipeline expansion in high unmet oncology indications, all of which GAS6/AXL pathway is active and relates to poor prognosis Advance CTGF discovery program to clinic Other potential discovery programs Plan to expand development team to execute company strategy Growth Strategy: Strengthen Company and Build Pipeline © 2020 Aravive, Inc.

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© 2020 Aravive, Inc. NASDAQ: ARAV; Shares Outstanding*: 15.0M basic Cash and cash equivalents*: $61M Cash and cash equivalents expected to enable the company to fund its current operating plans into 2022, depending on PROC P2/P3 design * As of March 31, 2020 Financials and Capitalization

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© 2020 Aravive, Inc. Uniquely positioned in competitive landscape Robust pipeline addressing significant drivers of mortality in oncology: metastasis and drug resistance AVB-500: high affinity decoy protein, a potent and selective drug that targets GAS6/AXL signaling Validated pathway drives activation, migration, and invasion of abnormal cells Suppresses GAS6 to undetectable levels in early clinical studies; prolonged target engagement Safety and tolerability profile to date support use as combination and/or maintenance therapy Compelling early efficacy signal in platinum-resistant ovarian cancer No adverse events that limit dosing High AVB-500 levels predictive of anti-tumor activity; exposure-response relationship RP2D identified AVB-500 performs well in late line therapy, where the clinical need is great Plan to discuss Phase 2/3 trial with FDA later this year Additional programs advancing into the clinic in high need indications* Renal cell carcinoma IND open and expect to initiate later this year ISTs (bladder cancer and PROC) CTGF preclinical program *Recruitment and retention in clinical trials may be impacted by COVID-19 AVB-500 Offers First- and Potential Best-In-Class Opportunity in Oncology

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© 2020 Aravive, Inc. Thank You Halting Disease Progression in its Tracks