arav-8k_20200218.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): February 18, 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 8.01. Other Events.

On February 18, 2020, Aravive, Inc. (the “Company”) issued a press release announcing that the independent Data Monitoring Committee (DMC) has reviewed the open-label data following the first 28-day treatment cycle for the three patients in each of the two 15 mg/kg dosing cohorts of the Phase 1b portion of the Phase 1b/Phase 2 clinical trial of AVB-500 in patients with platinum-resistant recurrent ovarian cancer and unanimously recommended the study continue as planned with enrollment of patients into the 20mg/kg dose cohorts. The DMC did not identify any safety concerns with AVB-500. A copy of the press release is attached hereto as Exhibit 99.1 and is incorporated herein by reference.

In addition, the Company will be making several investor presentations over the next several weeks.  In connection with the presentations, the Company intends to discuss the investor presentation attached as Exhibit 99.2 hereto, which is incorporated herein by reference.

The press release attached as Exhibit 99.1 to this Current Report on Form 8-K and the corporate 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 information included in this Current Report on Form 8-K, the press release attached as Exhibit 99.1 hereto or the corporate presentation attached as Exhibit 99.2 hereto.

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

 

Aravive, Inc. Press Release, dated February 18, 2020

99.2

  

Investor Presentation, dated February 2020

 

 

 

 

 



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: February 18, 2020

ARAVIVE, INC.

(Registrant)

 

 

 

By:

 

/s/ Vinay Shah

 

Name:

 

Vinay Shah

 

Title:

 

Chief Financial Officer

 

 

 

 

 

arav-ex991_8.htm

Exhibit 99.1

Aravive Announces Dose Escalation of AVB-500 in Recurrent Platinum Resistant Ovarian Cancer Phase 1b Trial

 

Dose escalation of AVB-500 to 20mg/kg dose follows positive recommendation by independent Data Monitoring Committee review

 

Plan to initiate Phase 2/3 study in Platinum Resistant Ovarian Cancer by year end 2020

 

 

HOUSTON Feb 18,  2020 – Aravive, Inc. (Aravive) (NASDAQ:ARAV) today announced that the independent Data Monitoring Committtee (DMC) has reviewed the open-label data following the first 28-day treatment cycle for the three patients in each of the two 15 mg/kg dosing cohorts of the Phase 1b portion of the Phase 1b/Phase 2 clinical trial of AVB-500 in patients with platinum-resistant recurrent ovarian cancer (PROC) and unanimously recommended the study continue as planned with enrollment of patients into the 20mg/kg dose cohorts. The DMC did not identify any safety concerns with AVB-500.

 

On November 20, 2019, Aravive reported data from the first 31 patients treated at the 10mg/kg dose supporting a relationship between AVB-500 blood levels and anti-tumor response, confirming the company’s strategy to investigate higher doses of AVB-500, specifically 15 and 20 mg/kg every two weeks.

“We are very pleased to receive this positive recommendation by the DMC and that AVB-500 continues to be well-tolerated as predicted from toxicology studies,” said Laura Bonifacio, Pharm.D., Ph.D., vice president of clinical operations of Aravive. “Our data modeling has predicted a dose of 20 mg/kg should allow at least 90% of the patients to achieve the desired high drug exposure levels of AVB-500 that correlated to better outcomes in our clinical studies to date.”

The company anticipates reporting safety and pharmacokinetic data from this Phase 1b trial in mid-2020 with plans to present preliminary efficacy in 2H 2020. The company plans to initiate a randomized Phase 2/3 study in PROC by end of 2020.

 


 

 

About Platinum-resistant, Recurrent Epithelial Ovarian Cancer (PROC) In the United States, ovarian cancer ranks fifth in cancer deaths among women, accounting for more deaths than any other cancer of the female reproductive system. It is estimated that in 2020 in the United States, more than 21,000 women will develop ovarian cancer and there will be approximately 13,940 attributed deaths.

About the Phase Ib/Phase 2 Recurrent Platinum Resistant Ovarian Cancer Trial

The open label Phase 1b safety lead-in portion of the efficacy and safety study of AVB-500 in patients with platinum-resistant recurrent ovarian cancer is enrolling patients into two cohorts, one investigating a combination of AVB-500 with pegylated liposomal doxorubicin, and the other, a combination of AVB-500 with paclitaxel. The primary objectives are to assess safety and tolerability of the combinations and to identify the dose for the Phase 2 portion of the study. The clinical trial will also explore secondary endpoints including preliminary activity measures and effects on biomarkers (GAS6-AXL) in serum and tumor tissues. The trial is listed on clinicaltrials.gov NCT03639246.

 

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 doing so, AVB-500 selectively inhibits the GAS6-AXL signaling pathway. In preclinical studies, GAS6-AXL inhibition has shown anti-tumor activity, both as a single agent and 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 is correlated to poor prognosis and survival, and has been implicated in therapeutic resistance to conventional chemotherapeutics and targeted therapies.

 

Aravive reported positive data from the first 31 patients enrolled in the Phase 1b portion of a Phase 1b/2 clinical trial of AVB-500 in platinum-resistant recurrent ovarian cancer. AVB-500 continues to be well tolerated with no dose limiting toxicities. An investigator-sponsored Phase 1 study of AVB-500, in combination with durvalumab in patients with platinum-resistant recurrent epithelial ovarian cancer, is also ongoing. Based on AVB-500’s safety profile and specifically targeted mechanism of action, this drug candidate has the potential to be used both in combination with existing therapies, as well as a maintenance drug. The U.S. Food and Drug Administration granted Fast Track Designation to AVB-500 in platinum-resistant recurrent ovarian cancer.

 

About Aravive

Aravive, Inc. (Nasdaq: ARAV) is a clinical-stage biopharmaceutical company developing treatments designed to halt the progression of life-threatening diseases, including cancer and fibrosis. Aravive’s lead product candidate, AVB-500, is an ultra-high affinity decoy protein that targets the GAS6-AXL signaling pathway. By capturing serum GAS6, AVB-500 starves the AXL pathway of its signal, potentially halting the biological programming that promotes disease progression. AXL receptor signaling plays an important role in multiple types of malignancies by promoting metastasis, cancer cell survival, resistance to treatments, and immune suppression. The GAS6-AXL signaling pathway also plays a significant role in fibrogenesis. Aravive is evaluating AVB-500 in platinum-resistant ovarian cancer, clear cell renal cell carcinoma

 


 

 

(ccRCC) and kidney fibrosis and intends to expand development into additional oncology and fibrotic indications. Aravive is based in Houston, Texas and received a Product Development Award from the Cancer Prevention & Research Institute of Texas (CPRIT) in 2016. 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, concerning a dose of 20 mg/kg should allow at least 90% of the patients to achieve the desired high drug exposure levels of AVB-500 that correlated to better outcomes in our clinical studies to date, reporting safety and pharmacokinetic data from the Phase 1b study in mid-2020 with plans to present preliminary efficacy in 2H 2020, plans to initiate a randomized Phase 2/3 study in PROC by end of 2020, the potential of AVB-500 to be used both in combination with existing therapies, as well as a maintenance drug, the potential of AVB-500 to halt the biological programming that promotes disease progression and the expansion of the development of AVB-500 into additional oncology and fibrotic indications. 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 achieve the desired high drug exposure levels of AVB-500, report data as planned, complete the Phase 1b portion of the Phase1b/2 in time to initiate a Phase 2/3 trial in PROC by end of 2020,expand development in 2020 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 studies, 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; 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; potentialdifficulties 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 and Form 10-K/A for the fiscal year ended December 31, 2018, 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 for Aravive:

 

Investors:

Christina Tartaglia

Stern Investor Relations

christina@sternir.com

 

Media:

Heidi Chokeir, Ph.D.

 


 

 

Canale Communications

heidi@canalecomm.com

619-203-5391

 

Source: Aravive

 

 

 

 

 

arav-ex992_9.pptx.htm

Slide 1

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

Slide 2

Important Information © 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, 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; 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

Company Overview The Company Lead Clinical Program (AVB-500) 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 (hdqtrs.) and Palo Alto, CA $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 clinical and program milestones during 2020 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 Currently in expanded Phase 1b/2 for platinum-resistant ovarian cancer; Fast-track designation granted by the FDA Ideal profile for combination with chemo, check-point inhibitors and PARP inhibitors in broad range of indications IP coverage through 2033 and beyond Our approach draws on novel insights into targeting signaling pathways that drive the activation, migration and invasion of abnormal cells into healthy tissues © 2020 Aravive, Inc.

Slide 4

Pipeline Focused on GAS6/AXL Signaling in Oncology & Fibrosis Indication Preclinical Phase 1 Phase 1 *Phase 1b Phase 3 AVB-S6-TBD Ovarian Cancer platinum resistant (chemo combo) Clear Cell Renal Cancer 3rd Oncology (undisclosed indication) Kidney Fibrosis (IgAN) Chronic Fibrosis (undisclosed indication) AVB-500 Status: IND Open Status: P1b expansion to confirm early efficacy signal Status: Recruiting © 2020 Aravive, Inc. Ovarian Cancer platinum resistant (PD-L1i combo) Status: Recruiting IST= investigator sponsored trial Status: Not Initiated * Phase 1 was conducted in healthy volunteers, allowing any next AVB-500 study to be either phase 1b or phase 2 study Phase 2 Phase 2aPhase 2b IST with AstraZeneca

Slide 5

AXL Tyrosine Kinase Promotes Invasion, Metastasis, and Resistance 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 Figure from Clinical Science Apr 01, 2012, 122 (8) 361-368 © 2020 Aravive, Inc. 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

Slide 6

GAS6/AXL Signaling: Decoy Receptor is the Best Approach for Potent and Selective Inhibition WT AXL has pM Affinity; AVB-500 AXL Decoy has fM Affinity Selectivity limited by RTK homology Off-target toxicity Multiple resistance mechanisms Many potential competitors AXL or GAS6 Antibody Tyrosine Kinase Inhibitor 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 © 2020 Aravive, Inc. Decoy AXL Receptor

Slide 7

Other Drugs Targeting AXL Signaling in Clinical Development are Not Selective Drug (Stage) Company Target Selective for AXL AVB-500 (Ph Ib/II) Aravive GAS6 YES Gilterinib (Market) Astellas AXL (Multi-kinase) NO Cabozantinib (Market) Exelixis AXL (Multi-kinase) NO Sitravatinib (Ph III) Mirati (BeiGene) AXL (Multi-kinase) NO Merestinib (Ph II) Lilly AXL (Multi-kinase) NO BGB324 (Ph II) BergenBio AXL (Multi-kinase) NO S49076 (Ph I/II) Servier 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 © 2020 Aravive, Inc. VS.

Slide 8

AVB-500: A Novel Approach to Selectively Inhibit AXL Signaling Decoy receptor engineered for very high affinity for GAS6 – ~200 fold greater than native AXL Favorable safety and PK profile GAS6 not needed by normal tissue GLP preclinical studies demonstrate ≥ 30-fold safety margin (relative to max feasible dose in tox; 3-month tox study completed) As biologic, does not compete for metabolism with chemotherapies; facilitates combination with other therapies Small molecules targeting AXL can have off target activities Strong IP position on GAS6 inhibition Proprietary biomarker tests to monitor GAS6 levels; serum GAS6 levels associated with efficacy in preclinical studies Robust CMC Drug candidate manufactured at high yield and purity AVB-500 Demonstrated Favorable Safety Profile and Proof-of-Mechanism in FIH Phase 1 Trial J Clin Invest. 2017;127(1):183–198 © 2020 Aravive, Inc.

Slide 9

Strong Rationale for Inhibiting GAS6/AXL Signaling with AVB-500 in Platinum Resistant Metastatic Ovarian Cancer Expression in 0% (0/10) of normal ovarian tissue Expression in 73% (219/297) ovarian tumor samples including low grade serous, endometroid and advanced stage tumors1 Preclinical in vitro 1,2,3 Inhibition decreases invasion/migration Preclinical in vivo 1,2,3 Inhibition decreases tumor Correlates with chemoresistance to carboplatin and paclitaxel Inhibition improves sensitivity to platinum and taxane therapies Strong Scientific Rationale in Ovarian Cancer © 2020 Aravive, Inc.

Slide 10

AVB-500: Clinical Program Currently in Expanded Phase 1b/2 Trial With Early Proof-of-Concept Data Fast-track designation granted by the FDA for platinum-resistant ovarian cancer; 10 and 15 mg/kg dose enrollment completed & now enrolling 20 mg/kg dose Well-tolerated to date and no anticipated drug-drug interactions facilitate combination studies (unlike small molecules) The ability to combine with common standards of care allows access to a large total accessible market Robust chemistry manufacturing control with high yield and purity © 2020 Aravive, Inc.

Slide 11

Key Eligibility Criteria for P1b Study in Platinum-Resistant Ovarian Cancer NOS= Not Otherwise Specified | ECOG= Eastem Cooperative Oncology Group © 2020 Aravive, Inc. 1-3 prior lines Measurable disease Platinum free interval ≤ 6mo after most recent platinum-containing regimen Adenocarcinoma NOS, high grade endometroid adenocarcinoma, mixed epithelial (≥ 80% high grade serous), high grade serous, or undifferentiated carcinoma ECOG performance status 0-1

Slide 12

Currently in 20 mg/kg cohort of P1b Study of AVB-500 in Platinum-Resistant Ovarian Cancer AVB-500 (AVB): Initial dose 10 mg/kg q14 days Pegylated liposomal doxorubicin (PLD): 40 mg/m2 d1; 28 day cycle Paclitaxel (PAC): 80 mg/m2 day 1, day 8, day 15; 28-day cycle Maintenance dosing on AVB-500 monotherapy upon completion of PLD / PAC Trial Design (NCT03639246) © 2020 Aravive, Inc. AVB 500 10 mg/kg + PLD AVB 500 15 mg/kg + PLD AVB 500 20 mg/kg + PLD Enrollment complete 31 patient data published Nov 2019 Enrollment complete iDMC review iDMC review Select RP2D iDMC review Platinum Resistant Ovarian Cancer 1-3 prior lines 40 pts 6 pts 12 pts AVB 500 10 mg/kg + PAC AVB 500 15 mg/kg + PAC AVB 500 20 mg/kg + PAC Currently enrolling iDMC= Independent Data Monitoring Committee

Slide 13

Safety data for the first 31 patients: AVB-500 (10mg/kg) well-tolerated No serious and unexpected adverse reactions No dose limiting toxicities Infusion reactions managed by premedication regimen 40 patients total have been dosed at 10mg/kg Similar safety profile as that seen with first 31 patients 6 patients have been dosed at 15mg/kg Similar safety profile to the 10mg/kg dose iDMC reviewed and allowed escalation to 20mg/kg dose © 2020 Aravive, Inc. Safety Summary from Phase 1B PROC Study to Date iDMC= Independent Data Monitoring Committee

Slide 14

Exposure-Response Analysis Demonstrated AVB-500 Levels at 10mg/kg Dose Predict Clinical Benefit © 2020 Aravive, Inc.   Above Minimal Efficacious Exposure Below Minimal Efficacious Exposure Number of Patients (n) 17 14 Complete Response (CR) 1 (6%) 0 Partial Response (PR) 4 (24%) 2 (14%) Overall Response Rate (ORR) 5 (29%) 2 (14%) Stable Disease (SD) 9 (53%) 4 (28%) Clinical Benefit (SD+ORR) 14 (82%) 6 (43%) Median DOR (months) 7.62  3.96 Median PFS (months) 8.1 1.8 Progressive Disease (PD) 3 (18%) 8 (57%) Patients remaining on study as of Oct 31 2019 8 (47%) 0 Sufficient AVB-500 exposures doubled ORR, Clinical Benefit Rate (CBR), and duration of response Response rate in below minimal efficacious exposure patients consistent with historical control rates of 10-15% for PAC or PLD PFS will be primary endpoint for registration study Best Response Determined by Investigator-Assessed RECIST 1.1

Slide 15

AVB-500 (10mg/kg) + Chemo Shows Improved Clinical Benefit in Patient Subsets That Generally Respond Poorly to Chemo ORR= objective response rate; CR=complete response; PR=partial response; SD=stable disease; CBR=clinical benefit rate; PD=progressive disease Historical control data from European Journal of Obstetrics & Gynecology and Reproductive Biology 166 (2013) 94–98 22 patients in AVB-500 +chemo group overall; 11 patients in the high exposure AVB-500+chemo group and 99 patients from Bruchim paper AVB-500 AVB-500 High Exposure AVB-500 AVB-500 High Exposure AVB-500 AVB-500 High Exposure AVB-500 AVB-500 High Exposure

Slide 16

AVB-500 (10mg/kg) + Chemo Shows Improved Clinical Benefit in Patient Subsets That Generally Respond Poorly to Chemo Historical control data from Cancer Chemotherapy and Pharmacology (2019) 84:33-39 37 12 patients in AVB-500 +chemo group overall, 6 patients in the high exposure AVB-500 +chemo group and 21 in Kobayashi-Kato paper One responder in chemo + AVB-500 high exposure group had CR and no CRs in control (1 PR in control) ORR= objective response rate; CR=complete response; PR=partial response; SD=stable disease; CBR=clinical benefit rate; PD=progressive disease; PFI=Platinum Free Interval AVB-500 AVB-500 High Exposure AVB-500 AVB-500 High Exposure AVB-500 AVB-500 High Exposure AVB-500 AVB-500 High Exposure

Slide 17

Best Response Determined by Investigator-Assessed RECISTv1.1 for First 31 Patients (10mg/kg): One CR © 2020 Aravive, Inc. Note: 2 pts who were PD at best response (Pac arm) are excluded from the waterfall PLD Pac High exposure patients

Slide 18

Summary of First 31 Patients’ Response as of October 31 2019 CT Scans PAC PLD Partial response Progressed Complete response Stable disease represented by continuous bar * * * * * * * * * * * * * * * * * * High exposure patients Withdrew consent and off study © 2020 Aravive, Inc. As of Oct 31, 2019 patient remained on AVB-500 monotherapy for ~6 mos

Slide 19

Comparable Demographics and Baseline Characteristics Confirming AVB-500 Exposure Drives Anti-Tumor Activity Above Minimal Efficacious Concentration Below Minimal Efficacious Concentration Age, years median (min, max) 71 (52-82) 63.0 (53-80) Prior lines* 1 (%) 6 (35.3%) 2 (14.3%) 2 (%) 8 (47.1%) 6 (42.9%) 3 (%) 3 (17.6%) 5 (35.7%) Platinum Free Interval ≥ 3mo 11 (64.7%) 8 (57.1%) < 3mo 6 (35.3%) 6 (42.9%) ECOG 0 11 (64.7%) 6 (42.9%) 1 6 (35.3%) 8 (57.1%) * PAC PT IN BELOW MINIMAL EFFICACIOUS GROUP MISSING VALUE © 2020 Aravive, Inc.

Slide 20

Next Steps Data confirm strategy to investigate higher doses in the current Phase 1b study to determine if a greater proportion of patients achieve high drug exposure levels PK modeling predict a dose of 20 mg/kg should allow >90% of patients to achieve desired high exposure levels Anticipate 18-24 more patients across both cohorts and at 15 and 20mg/kg Will evaluate percentage of patients achieving minimal efficacious concentration and correlate to response rates Anticipate PK and safety read-out middle of 2020 for 15 and 20mg/kg © 2020 Aravive, Inc.

Slide 21

Randomized Ph 2/3 Study Following Completion of Ph 1 Dose Escalation in PROC Patients: P1b Will Determine RP2D Anticipate initiating 2H20 Same population as P1b portion Effect size from P1b (all AVB-500 doses) will drive regulatory strategy, statistical plan, Ns Randomized (2:1), double-blind, placebo- controlled study to compare efficacy and tolerability of AVB-500 in combination with PLD or Pac versus placebo plus PLD or Pac Primary objective to assess anti-tumor activity of AVB-500 in combination with Pac Or PLD as measure by PFS Secondary objectives include assessment of PK/PD and additional efficacy endpoints (ORR, OS, DOR, DCR) Platinum Resistant Ovarian Cancer 1-3 prior lines PLD SOC + placebo SOC= standard of care; PLD or PAC SOC + AVB-500 © 2020 Aravive, Inc.

Slide 22

Rationale for AVB-500 in Kidney Cancer Strong biological rationale for clear cell Renal Cell Cancer1 VHL tumor suppressor gene mutated, causes increase in AXL AXL/GAS6 levels predict prognosis & survival in human1 Strong in vivo activity in preclinical models1,2 Single agent Combo with TKI 2 Xiao et al, Cancer Research October 4, 2019; © 2020 Aravive, Inc. 1 Rankin et al, PNAS | September 16, 2014 | vol. 111 | no. 37 | 13375

Slide 23

Overview of P1b/P2 Clear Cell Renal Cell Carcinoma Positioning AVB-500 in the Evolving Treatment Landscape Histologically confirmed stage IV ccRCC (according to the American Joint Commission on Cancer, seventh edition, classification) progressed on/after or intolerant to 1L Cabozantinib is used most frequently after IO Cabozantinib being tested in 1L with nivo in CM-9ER vs sunitinib Positive 2L data of AVB-500 combined with cabozantinib creates opportunities for expansion Phase 1b safety run-in with AVB-500 in combination with cabozantinib Up to 18 patients in P1b, ability to increase/decrease dose based on tolerability, pk/pd 90 patients in P2 controlled, randomized, blinded portion Primary endpoint in P2 is PFS; Secondary endpoints: ORR, DOR, DCR, and OS

Slide 24

AXL Promotes a Suppressive Myeloid Micro-environment ISTs Investigating Combinations of AVB-500 + PDL1 inhibitor AXL presence Decreases tumor T cells (killer) infiltration Decreases Tumor antigen presentation Increases suppressive myeloid cells and macrophages AXL loss Increases Tumor antigen expression Decreases suppressive myeloid cells and macrophage Increases Tumor T cell infiltration Sensitizes tumor cells to checkpoint immunotherapy when they were previously resistant AXL expressed in patients unresponsive to PD-1/PD-L1 immunotherapy Adapted from NATURE COMMUNICATIONS | 7:13898 | DOI: 10.1038/ncomms13898 | © 2020 Aravive, Inc.

Slide 25

Strong biological rationale for IgA nephropathy (IgAN)1 GAS6 is more highly expressed in IgAN tissue relative to normal tissue GAS6 stimulates mesangial cell proliferation GAS6 expression correlates with severity of IgA Nephropathy and predict prognosis in humans Strong in vivo activity in preclinical models2 Rationale for Inhibiting GAS6/AXL Signaling in Kidney Fibrosis 1 Coppo et al, Kidney Intl (2014) 86:828-36; Reich et al, J Am Soc Nephrol (2007) 3177-83; Nagai K, Miyoshi M, Kake T, Fukushima N, Matsuura M, et al. (2013) Dual Involvement of Growth Arrest-Specific Gene 6 in the Early Phase of Human IgA Nephropathy. PLoS ONE 8(6): e66759. doi:10.1371/journal.pone.0066759 GAS6 acts as a mitogen, stimulating mesangial cell proliferation through binding to its cell-surface receptor AXL Mesangial proliferation is a hallmark of IgAN M. Yanagita, et al. (1999) J Am Soc Nephrol 10: 2503–2509. 2 Yanigati et al, (2001) Am J Pathol. Apr; 158(4): 1423–1432; Zhen et al Journal of Autoimmunity 93 (2018) 37–44 © 2020 Aravive, Inc.

Slide 26

Overview of Phase 2A IgAN Study Small (N of 12-24) Proof of Concept Study in IgA patients Sites in USA and Ukraine Diagnosis of biopsy-proven IgAN Proteinuria ≥ 1g to 3g/24hr Monitor safety, PK/PD Ensure sGAS6 levels suppressed throughout dosing interval Open-label Monitor proteinuria and other renal functions Ability to increase dose based on data © 2020 Aravive, Inc.

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Experienced, Methodical, Efficient Development Execution Strong Clinical Development Team © 2020 Aravive, Inc. 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 4Q2019- Kidney fibrosis trial initiation 1Q 2020- IND open for ccRCC study Mid-2020- Safety and PK from Ph1b Ovarian (from 15 and 20 mg/kg doses) 2H-2020- P2/P3 Platinum-resistant ovarian cancer initiation 2020- Potential preliminary safety and early efficacy from ongoing trials in kidney fibrosis and ccRCC 2019 Achieved MilestonesUpcoming Milestones IND= investigational new drug application; POM=proof of mechanism; POC=proof of concept

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Financials and Capitalization NASDAQ: ARAV; Shares Outstanding*: 14.9M basic * As of September 30, 2019 adjusted for net proceeds from recent public offering, closed on December 2, 2019 Cash and cash equivalents*: $70M Cash and cash equivalents expected to enable the company to fund its operating plans through 2021 © 2020 Aravive, Inc.

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AVB-500 Offers First- and Best-In-Class Opportunity in Oncology Uniquely positioned in competitive landscape Robust pipeline addressing significant drivers of mortality in oncology and fibrosis: metastasis and drug resistance © 2020 Aravive, Inc. AVB-500: high affinity decoy protein, a potent and selective drug 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; statistically significant association with PFS In first 31 patients, median PFS for patients with high drug levels was statistically significantly longer than those with low drug levels Expanded P1b portion to validate efficacy signal, evaluate higher doses and explore the most efficient regulatory path to approval Additional programs advancing into the clinic in high need indications Kidney fibrosis (IgA nephropathy) trial recruiting Renal cell carcinoma IND open ISTs

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