arav-8k_20190812.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): August 12, 2019

 

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 8.01Other Events

 

Aravive, Inc. (the “Company”) will be making several investor presentations over the next several weeks. In connection with the presentations, the Company intends to discuss the slide presentation attached as Exhibit 99.1 hereto, which is incorporated herein by reference.

 

The slide presentation attached as Exhibit 99.1 to this Current Report on Form 8-K includes “safe harbor” language pursuant to the Private Securities Litigation Reform Act of 1995, as amended, indicating that certain statements contained in the slide presentation 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 or the slide presentation attached as Exhibit 99.1 hereto.

 

 

Item 9.01.Financial Statements and Exhibits

(d) Exhibits.

The following exhibit is filed with this Current Report on Form 8-K:

 

 

 

 

Exhibit
Number

  

Description

 

 

99.1

  

Aravive, Inc. Investor Presentation dated August 2019

 

 


 

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: August 12, 2019

ARAVIVE, INC.

(Registrant)

 

 

 

By:

 

/s/ Jay P. Shepard

 

Name:

 

Jay P. Shepard

 

Title:

 

Chief Executive Officer

 

 

 

arav-ex991_141.pptx.htm

Slide 1

Aravive Corporate Presentation August 2019 © 2019 Aravive, Inc. Exhibit 99.1

Slide 2

Important Information 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. © 2019 Aravive, Inc.

Slide 3

Aravive Offers First and Potentially Best-In-Class Opportunities in Oncology and Fibrosis © 2019 Aravive, Inc. Uniquely positioned in competitive landscape Robust pipeline addressing significant drivers of mortality in oncology and fibrosis: metastasis and drug resistance 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 Proprietary biomarker accelerates clinical development, identify pharmacologically active dose early in development Safety and tolerability profile to date support use as combination and/or maintenance therapy Compelling early efficacy signal in platinum-resistant ovarian cancer No safety signal observed Expanded P1b portion to validate efficacy signal and explore the most efficient regulatory path to approval Detailed safety, efficacy and PK/PD data anticipated to be presented at upcoming scientific meeting Additional programs advancing into the clinic in high need indications Kidney fibrosis (IgA nephropathy) trial initiation anticipated in 4Q 2019 Renal cell carcinoma trial initiation anticipated in 4Q 2019/1Q2020

Slide 4

Robust Development Pipeline in Oncology and Fibrosis © 2019 Aravive, Inc. **Phase 1 was conducted in healthy volunteers, allowing any next AVB-500 study to be either a phase 1b or phase 2 study Expansion into additional oncology indications where pre-clinical and biological rationale is strong Indication Preclinical Phase 1 Phase 2 Phase 3 Phase 1* Phase 1b AVB-S6-TBD Ovarian platinum resistant Clear Cell Renal Cell Carcinoma 3rd Oncology (undisclosed indication) Kidney Fibrosis Chronic Fibrosis (undisclosed indication) AVB-500 Status: Initiation expected 2019/early 2020 Status: Expansion underway to confirm early efficacy Status: Initiation expected 2019

Slide 5

GAS6-AXL Role in Cancer: Strong Biology, but Challenging Target with Poor Drugs Identified at Stanford by Aravive’s scientific founder Increased GAS6/AXL expression and signaling seen in many cancers and correlated with a poor prognosis Robust target validation: differentially expressed in cancer, activation drives cancer, blockade inhibits cancer Extensive growing literature on AXL/GAS6 all pointing in the same direction Strong biology Challenging target with poor drugs due to lack of selectivity and potency 2000à 2016 © 2019 Aravive, Inc. Examples AXL/GAS6 Up-Regulation References Ovarian* 50-90% Rankin et al., 2010 Sun et al., 2004 Kidney* >75% Gustafsson et al., 2009 Chung et al., 2003 Breast* 76-90% Zhang et al., 2008 Berclaz et al., 2001 McCormack et al., 2008 Lung* 45-93% Shieh et al., 2005 Wimmel et al., 2001 Linger et al., 2012 AML, CML* >35% Rochlitz et al., 1999 Gioia et al., 2011 Pancreas* 50-70% Song et al., 2011 Koorstra et al., 2009 *Available Preclinical data with AVB-500

Slide 6

AVB-500 Inhibits AXL Signaling by Neutralizing GAS6 Addresses Potency and Selectivity Challenges of Targeting GAS/AXL Pathway Modified AXL-Fc fusion protein engineered for strong stability and very high affinity for GAS6 Kd for human GAS6 is ~140 femtomolar ~200 fold greater affinity for human GAS6 compared to native AXL receptor Favorable safety and PK profile No anticipated off-target toxicity given GAS6 not needed by normal tissue No anticipated drug‐drug interactions facilitate combination studies Structure modeled after marketed drugs: E.g., Enbrel®, Zaltrap®, Orencia® Competitors targeting AXL; none directly targeting GAS6 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 © 2019 Aravive, Inc.

Slide 7

GAS6/AXL Signaling Drives Activation, Migration and Invasion of Abnormal Cells Inhibiting GAS6 preclinically Has anti-tumor activity in many tumor types, including ovarian, pancreatic, breast, and kidney Blocks tumor invasion & metastasis Overcomes acquired drug resistance Ameliorates desmoplasia and fibrosis Enhances tumor immune response GAS6 is redundant for normal tissues GAS6 depletion well tolerated Lack of adverse events provides large therapeutic index GAS6 depletion readily combinable with targeted therapies, immunotherapies and radiotherapy © 2019 Aravive, Inc. GAS6: Sole Ligand for AXL and no Ligand Independent Activation of AXL High affinity GAS6-AXL binding ~30 pM GAS6 Signaling Immune Suppression Resistance to: Chemotherapy Radiotherapy Targeted therapy Resistance to apoptosis/ autophagy Proliferation EMT and Metastasis

Slide 8

AVB-500: Dual Modes Act on Tumor Directly and Tumor Microenvironment to Address Metastasis © 2019 Aravive, Inc. Source: https://www.centerwatch.com/drug-information/fda-approved-drugs/therapeutic-area/12/oncology Tumor micro environment drugs include anti-angiogenic agents Avastin and Zaltrap

Slide 9

Decoy Receptor is the Best Approach for Potent and Selective Inhibition of GAS6/AXL Signaling © 2019 Aravive, Inc. WT AXL has pM Affinity; AVB-500 has fM Affinity Selectivity limited by RTK homology Off-target toxicity Multiple resistance mechanisms Many potential competitors Decoy AXL Receptor 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 Strong IP position kinase domain

Slide 10

© 2019 Aravive, Inc. Our Molecules Achieve Prolonged Target Engagement with High Potency & Selectivity For Improved Activity *Established Metastatic Disease **Methods in Rankin et al 2012 J Clin Invest. 2017;127(1):183–198 Affinity (potency) Matters Selectivity Matters In vivo Activity Matters

Slide 11

Development Program in Platinum-Resistant Ovarian Cancer Initial indication with robust preclinical biological rationale, unmet clinical needs, and feasibility to establish POC © 2019 Aravive, Inc.

Slide 12

Attractive Drug Attributes Biomarker driven clinical development to accelerate program Low toxicity and no anticipated drug-drug interactions facilitate combination studies (unlike small molecules) © 2019 Aravive, Inc. 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

Slide 13

Aravive’s Innovative Development Plan Accelerates Time to POC Year 1 Year 2 Year 3 Year 4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 *http://www.appliedclinicaltrialsonline.com/why-are-cancer-clinical-trials-increasing-duration Abbreviations: IND= Investigational New Drug application; PD= pharmacodynamic; POM-proof of mechanism; POC=proof of concept Aravive using PD Marker Typical Oncology Plan Normal Volunteer Phase 1 (40 pts) Phase 1b/2 in Cancer Patients (~100) Phase 1a single agent study in end stage cancer patients “all comers” or select population 20-30+ patients* Phase 2 Cancer Patients (~100 pts) IND POM POC IND POM POC ~1-2 years difference © 2019 Aravive, Inc. slide for illustrative purposes only not actual committed timelines

Slide 14

Trial Design Dosed 42 Healthy Volunteers Two-dosing regimens: SAD portion consisting of 4 sequential dose escalation cohorts RD portion consisting of 4 single doses once weekly Primary objective to assess safety and tolerability Secondary objective to assess PK/PD and to establish proof-of-mechanism Top-line Results Treatment-emergent adverse events generally mild, transient and self-limiting. No serious or dose-related adverse events reported. Serum GAS6 levels suppressed until weeks 3 and 4 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 10 mg/kg every other week selected as the initial dose in the Phase 1b clinical trial © 2019 Aravive, Inc. AVB-500 Demonstrates Tolerability & Proof-of-Mechanism in Phase 1 Trial A Single-blind, Randomized, Placebo-controlled, Phase 1, Single Ascending-dose (SAD) and Repeat-dose (RD), Safety and Tolerability Study of Intravenous AVB-500 in Healthy Subjects Status: Completed, data presented at EORTC-NCI-AACR 2018

Slide 15

Platinum Resistant Ovarian Cancer: Compelling Efficacy Signal in Phase 1b Portion of Phase 1b/2 Study Safety lead-in portion of the Phase 1b/2 trial is designed to confirm dose predicted based on Phase 1 study in healthy volunteers Primary objective to assess safety and tolerability; Secondary objective to assess PK/PD and efficacy Exploratory objectives include exploration of efficacy endpoints in biomarker (GAS6, AXL) defined populations based on expression of those biomarkers in serum and/or tumor tissue © 2019 Aravive, Inc. Status: Phase1b Expanded to Confirm Early Efficacy Signal Phase 1b Trial Design Pac = Paclitaxel PLD = Pegylated Liposomal Doxorubicin AVB-500 + Pac N = 6 AVB-500 + PLD N = 6 AVB-500 + Pac N = 18 AVB-500 + PLD N = 18 Dose Confirmation Cohorts* Expansion Cohorts *Ability to dose titrate based safety, tolerability, and PK/PD *Ability to dose titrate based safety, tolerability, and PK/PD Total N = 48 Platinum Resistant Ovarian Cancer 1-3 prior lines, normal GI Overall Best Response Rate in AVB-500 Combination Cohorts Greater than Historically Observed Response Rates with Standard of Care

Slide 16

Response Rates for Standard of Care in Platinum Resistant Ovarian Cancer are Well-Established at ~11% (10-15%) Primary References: (1) J Clin Oncol. 2007 Jul 1;25(19):2811-8 (2) J Clin Oncol. 2010 Jul 1;28(19):3107-14 (3) J Clin Oncol. 2012 Nov 1;30(31):3841-7 (4) J Clin Oncol. 2013 Dec 10;31(35):4400-6 (5) J Clin Oncol. 2001 Jul 15;19(14):3312-22. (6) J Clin Oncol. 1997 Jun;15(6):2183-93. (7) Acta Oncol. 2002;41(5):418-24. (8) J Clin Oncol. 2008 Feb 20;26(6):890-6 (9) Journal of Clinical Oncology 2019 37:15_suppl, 5507-5507 (10) J Clin Oncol. 2014 May 1;32(13):1302-8, J Clin Oncol. 2015 Nov 10;33(32):3836-8 (11) Gynecol Oncol. 2011 Jul;122(1):111-5 (12) Lancet Oncol. 2014 Jul;15(8):799-808. (13) Eur J Cancer. 2009 Sep;45(13):2324-32. (14) Annals of Oncology (2018) 29 (suppl_8): viii332-viii358 © 2019 Aravive, Inc. Comments: [a] Patients had fewer lines of therapy relative to AVB500-OC-002 [b] Not all patients had measurable disease at baseline [c] Response rate included patients who were platinum sensitive [d] Patients could not have more than 1 prior platinum containing regimen [e] Response rate not presented separately for other chemotherapies (eg CLIO included physician choice of PLD/PAC/Topo/Gem; canfosfamide study included physician choice of PLD/Topo; CORAIL included physician choice of PLD/Topo; AURELIA study grouped PLD/PAC and TOPO response rates together) [f] Central reader assessed rates Review paper: Davis et al, Gynecologic Oncology 133 (2014) 624–631 Study (Ref#) GEM vs PLD Ph3 (1) Trabectedin (2) Patupilone Ph3 (3) PRECEDENT (4) PLD vs TOPO Ph3 (5) TOPO vs PAC, Ph3 (6) Weekly vs Q3W PAC (7) Gem vs PLD Ph3 (8) CLIO (9) AURELIA (10) GOG 126- (11) TRINOVIA-1 (12) Canfosfamide Ph3 (13) CORAIL (14) PLD 7/60 (11.7%) 14/115 (12%) 33/416 (8%) 6/49 (12%) 16/130 (12%) - - 11/70 (16%) - 5/64 (8%) - - 23/217 (11%) 27/221 (12%) PAC - - - - - 3/26 (12%) 38/103 (37%) - - 16/55 (29%) 11/47 (23%) 129/433 (30%) - - PLD or PAC - - - - - - - - 2/19 (11%) 17/144 (11.8%) - - - - Comments   a b,c a, c a a d c e a, b, e a c e d

Slide 17

Platinum Resistant Ovarian Cancer Phase 1b/2 of AVB-500: Phase 2 Portion © 2019 Aravive, Inc. Status: FPI expected 4Q19/1Q20, topline interim analysis data expected end of 2020 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) Anticipated Phase 2 Trial Design Total N = 120 Platinum Resistant Ovarian Cancer 1-3 prior lines Pac Cohort N = 60 PLD Cohort N = 60 AVB-500 + Pac N = 40 Arm 1 Pac N = 20 AVB-500 + PLD N = 40 PLD N = 20 Arm 2 Arm 3 Arm 4 Pac = Paclitaxel PLD = Pegylated Liposomal Doxorubicin

Slide 18

AVB Proteins Offer Franchise with Demonstrated Tolerability and Early Activity in Cancer with PD Biomarker for Accelerated Development © 2019 Aravive, Inc.

Slide 19

Robust Development Pipeline in Oncology and Fibrosis © 2019 Aravive, Inc. **Phase 1 was conducted in healthy volunteers, allowing any next AVB-500 study to be either a phase 1b or phase 2 study Expansion into additional oncology indications where pre-clinical and biological rationale is strong Indication Preclinical Phase 1 Phase 2 Phase 3 Phase 1* Phase 1b AVB-S6-TBD Ovarian platinum resistant Clear Cell Renal Cell Carcinoma 3rd Oncology (undisclosed indication) Kidney Fibrosis Chronic Fibrosis (undisclosed indication) AVB-500 Status: Initiation expected 2019/early 2020 Status: Expansion underway to confirm early efficacy Status: Initiation expected 2019

Slide 20

Experienced, Methodical, Efficient Development Execution Strong Clinical Development Team Dev Plan Enabled Bifurcated Strategy- Oncology and Fibrosis 4Q 2017- IND filed 1Q 2018- FIH in NHV initiated 2Q 2018- POM in NHV 3Q 2018- Tolerability in NHV 4Q 2018- P1b in ovarian cancer initiated 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 3Q 2019 to 1Q20- Detailed data release on first cohort of Ph1b ovarian 4Q 2019- Phase 1b safety, PK/PD data in platinum-resistant ovarian cancer to confirm R2PD 4Q 2019- Kidney fibrosis trial initiation 4Q 2019/1Q2020- Renal cell carcinoma trial initiation 4Q 2019/1Q 2020- P2 Platinum-resistant ovarian cancer initiation 2020- Efficacy data roll out from P1b ovarian cancer as data mature 2020- Safety and early efficacy in kidney fibrosis © 2019 Aravive, Inc. Achieved Milestones Upcoming Milestones FIH=first in human; IND= investigational new drug application; POM=proof of mechanism; POC=proof of concept; R2PD=recommended P2 dose

Slide 21

Well Capitalized to Execute on Clinical Plans NASDAQ: ARAV; Shares Outstanding*: 11.3M basic © 2019 Aravive, Inc. * As of Q2 2019 Cash and cash equivalents*: $48.4M Cash and cash equivalents expected to enable the company to fund its operating plans through 2020

Slide 22

Aravive Opportunity Summary © 2019 Aravive, Inc. Strong biology addressing significant clinical need with competitive positioning Validated pathway drives activation, migration and invasion of abnormal cells AVB-500 PK/PD profile allowed seamless transition from preclinical to clinical studies Proprietary biomarker accelerates clinical development, identifying pharmacologically active dose more quickly Suppresses GAS6 to undetectable levels in early clinical studies (POM) Safety and tolerability profile to date support use as combination and/or maintenance therapy: solid CMC package Compelling early efficacy signal in platinum-resistant recurrent ovarian cancer No safety signal observed Cohort expansion underway to validate compelling efficacy signal in Phase 1b portion of Phase 1b/2 study Detailed safety, efficacy and PK/PD data anticipated to be presented at upcoming scientific meeting Additional programs advancing into the clinic in high need indications Robust pipeline addressing significant drivers of mortality in oncology and fibrosis: metastasis and drug resistance Kidney fibrosis (IgA nephropathy) trial initiation in 4Q 2019 Renal cell carcinoma trial initiation in 4Q 2019/1Q2020

Slide 23

Thank You © 2019 Aravive, Inc.