batiraxcept (AVB-500) / Aravive, WuXi AppTec, 3DMed - LARVOL DELTA

Synergistic correction of polycythemia vera phenotype via dual targeting of JAK2 and Gas6 in Jak2 exon 12 mutant mice (ASH 2025) - "Despite treatments like phlebotomy,cytoreduction, and JAK2 inhibitors (e.g., ruxolitinib, RUX), disease control is often insufficient...PV was induced at 5–7 weeks of age withtamoxifen... Gas6 deletion mitigates PV, supporting its role in controlling disease proliferation.Batiraxcept plus RUX reversed splenomegaly and normalized erythroid differentiation. Persistent highhematocrit despite normalized reticulocytes suggests longer treatment is needed. Preliminary datasuggest Gas6 also contributes to clotting abnormalities."

Preclinical • Hematological Disorders • Hematological Malignancies • Leukemia • Myelofibrosis • Myeloproliferative Neoplasm • Polycythemia Vera • Solid Tumor • Thrombosis • ABL1 • AXL • BCR • GAS6 • JAK2 • MERTK • TFRC

AXL inhibition improves the therapeutic efficacy of trastuzumab in high-risk endometrial cancer. (PubMed, Gynecol Oncol) - "Our findings support the combination of batiraxcept and trastuzumab as a promising therapeutic strategy for aggressive HER2+ endometrial cancer."

Journal • Endometrial Cancer • Endometrial Serous Adenocarcinoma • Oncology • Solid Tumor • Uterine Cancer • AURKA • LDHA • LRG1

COAXIN: Avelumab in Combination With AVB-S6-500 in Patients With Advanced Urothelial Carcinoma (clinicaltrials.gov) - P1 | N=19 | Active, not recruiting | Sponsor: University of Oklahoma | Trial completion date: Sep 2025 ➔ Feb 2026

Trial completion date • Oncology • Solid Tumor • Urothelial Cancer

Phase 1b/2 study of batiraxcept alone and in combination with cabozantinib with or without nivolumab for advanced clear cell renal cell carcinoma. (PubMed, Oncologist) - P1b/2 | "Batiraxcept was well tolerated with promising early efficacy signal when combined with cabozantinib, especially in heavily pretreated patients with ccRCC. The trial was discontinued early due to the sponsor's internal decision."

Journal • P1/2 data • Clear Cell Renal Cell Carcinoma • Fatigue • Genito-urinary Cancer • Kidney Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • AXL • GAS6

AVB-S6-500 and Durvalumab in Treating Patients With Platinum-Resistant or Recurrent Ovarian, Fallopian Tube, or Primary Peritoneal Cancer (clinicaltrials.gov) - P1/2 | N=12 | Terminated | Sponsor: M.D. Anderson Cancer Center | Completed ➔ Terminated; PI Request

Platinum resistant • Trial termination • Epithelial Ovarian Cancer • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Refractory Ovarian Cancer • Solid Tumor

COAXIN: Avelumab in Combination With AVB-S6-500 in Patients With Advanced Urothelial Carcinoma (clinicaltrials.gov) - P1 | N=19 | Active, not recruiting | Sponsor: University of Oklahoma | Trial completion date: Sep 2024 ➔ Sep 2025

Trial completion date • Oncology • Solid Tumor • Urothelial Cancer

Targeting AXL inhibits the growth and metastasis of prostate cancer in bone. (PubMed, Clin Cancer Res) - "Our study provides a robust preclinical rationale and mechanisms of action for using batiraxcept as a single agent or in combination with docetaxel or carboplatin to treat lethal mPCa."

Journal • Genito-urinary Cancer • Neuroendocrine Tumor • Oncology • Prostate Cancer • Solid Tumor • ALDH1A1 • E2F1 • NUSAP1 • TACSTD2

AVB-S6-500 and Durvalumab in Treating Patients With Platinum-Resistant or Recurrent Ovarian, Fallopian Tube, or Primary Peritoneal Cancer (clinicaltrials.gov) - P1/2 | N=12 | Completed | Sponsor: M.D. Anderson Cancer Center | Active, not recruiting ➔ Completed | Trial completion date: Aug 2025 ➔ Oct 2024

Trial completion • Trial completion date • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Refractory Ovarian Cancer • Solid Tumor

AVB-500 (Batiraxcept) in Combination With Paclitaxel in Recurrent High Grade Uterine Cancer (clinicaltrials.gov) - P1 | N=0 | Withdrawn | Sponsor: Washington University School of Medicine | N=36 ➔ 0 | Not yet recruiting ➔ Withdrawn

Enrollment change • Trial withdrawal • Endometrial Cancer • Oncology • Solid Tumor • Uterine Cancer • HER-2 • MSI

AVB-S6-500 and Durvalumab in Treating Patients With Platinum-Resistant or Recurrent Ovarian, Fallopian Tube, or Primary Peritoneal Cancer (clinicaltrials.gov) - P1/2 | N=12 | Active, not recruiting | Sponsor: M.D. Anderson Cancer Center | Trial completion date: Aug 2024 ➔ Aug 2025

Combination therapy • Trial completion date • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Refractory Ovarian Cancer • Solid Tumor

AVB-S6-500 and Durvalumab in Treating Patients With Platinum-Resistant or Recurrent Ovarian, Fallopian Tube, or Primary Peritoneal Cancer (clinicaltrials.gov) - P1/2 | N=12 | Active, not recruiting | Sponsor: M.D. Anderson Cancer Center | Trial completion date: Feb 2025 ➔ Aug 2024 | Trial primary completion date: Feb 2025 ➔ Aug 2024

Combination therapy • Trial completion date • Trial primary completion date • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Refractory Ovarian Cancer • Solid Tumor

AXLerate-OC/GOG-3059/ENGOT OV-66: Results of a phase 3, randomized, double-blind, placebo/paclitaxel-controlled study of batiraxcept (AVB-S6-500) in combination with paclitaxel in patients with platinum-resistant recurrent ovarian cancer. (ASCO 2024) - P3 | "The randomization was stratified by platinum-free interval (< 3 months, 3 to 6 months), prior lines (1 to 2, 3 to 4), and prior bevacizumab status (yes, no). The addition of batiraxcept to paclitaxel did not improve PFS or OS. However, in AXL high tumors, the PFS and OS were higher in participants who received batiraxcept with paclitaxel compared to paclitaxel alone."

Clinical • Combination therapy • Late-breaking abstract • P3 data • Oncology • Ovarian Cancer • Solid Tumor • AXL

AVB-500 (Batiraxcept) in Combination With Paclitaxel in Recurrent High Grade Uterine Cancer (clinicaltrials.gov) - P1 | N=36 | Not yet recruiting | Sponsor: Washington University School of Medicine | Trial completion date: Jan 2034 ➔ Jun 2034 | Trial primary completion date: Jan 2029 ➔ Jun 2029

Combination therapy • Trial completion date • Trial primary completion date • Endometrial Cancer • Oncology • Solid Tumor • Uterine Cancer • HER-2 • MSI

Batiraxcept-Paclitaxel Combination Shows Promise in High AXL-Expressing, Platinum-Resistant Ovarian Cancer (Physician’s Weekly) - P3 | N=366 | AXLerate-OC (NCT04729608) | Sponsor: Aravive, Inc. | "A total of 360 patients were 1:1 randomly assigned to paclitaxel plus batiraxcept or paclitaxel plus placebo. In the total population, no difference was observed in median PFS between participants treated with batiraxcept versus placebo: 5.13 (95% CI 4.16-6.1months) versus 5.49 (95% CI 5.27-5.7) months (HR 1.16; P=0.207). In addition, no difference was observed in median OS: 14.29 (95% CI: 12.5-16.0) months versus 14.39 (95% CI 12.7-16.0) months (HR1.07; P=0.689). However, in participants with high AXL-expression (n=61), defined as under or equal to 80% intensity on immunohistochemistry, median PFS was significantly improved by adding batiraxcept: 5.78 (95% CI 5.1-6.4) months versus 3.71 (95% CI 3.0-4.4) months (HR 0.55; P=0.042)."

P3 data • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor

Phase 1b study of batiraxcept in combination with durvalumab in patients with platinum-resistant ovarian cancer. (PubMed, iScience) - P1/2 | "Batiraxcept effectively reduced serum GAS6 levels at 1-h post-treatment, resulting in trough levels below the limit of detection in all cases but one. In conclusion, the combination of batiraxcept and durvalumab was safe and tolerable but did not demonstrate anti-tumor activity in a heterogenous population of patients with recurrent PROC."

Combination therapy • Journal • P1 data • Cystic Fibrosis • Fibrosis • Gene Therapies • Genetic Disorders • Immunology • Oncology • Ovarian Cancer • Pulmonary Disease • Respiratory Diseases • Solid Tumor • GAS6

Phase 1b Study of Batiraxcept in Combination with Durvalumab in Patients with Platinum-Resistant Ovarian Cancer (Cell Press, ScienceDirect) - P1/2 | N=12 | NCT04019288 | "The primary objective was to determine the toxicity profile of the combination. Eleven patients were enrolled on the trial. No dose-limiting toxicities were observed, and no objective responses were noted. Median PFS was 1.81 months (95% CI 1.71-2.40), and median OS was 4.53 months (95% CI 2.10-24.74). Batiraxcept effectively reduced serum GAS6 levels at 1-hour post-treatment, resulting in trough levels below the limit of detection in all cases but one."

P1 data • Gynecologic Cancers • Ovarian Cancer

Phase 1b Study of Batiraxcept in Combination with Durvalumab in Patients with Platinum-Resistant Ovarian Cancer (Cell Press, ScienceDirect) - P1/2 | N=12 | NCT04019288 | "The primary objective was to determine the toxicity profile of the combination. Eleven patients were enrolled on the trial. No dose-limiting toxicities were observed, and no objective responses were noted. Median PFS was 1.81 months (95% CI 1.71-2.40), and median OS was 4.53 months (95% CI 2.10-24.74). Batiraxcept effectively reduced serum GAS6 levels at 1-hour post-treatment, resulting in trough levels below the limit of detection in all cases but one."

P1 data • Gynecologic Cancers • Ovarian Cancer

AVB-500 (Batiraxcept) in Combination With Paclitaxel in Recurrent High Grade Uterine Cancer (clinicaltrials.gov) - P1 | N=36 | Not yet recruiting | Sponsor: Washington University School of Medicine | Trial completion date: Aug 2033 ➔ Nov 2033 | Initiation date: Dec 2023 ➔ Mar 2024 | Trial primary completion date: Aug 2028 ➔ Nov 2028

Combination therapy • Trial completion date • Trial initiation date • Trial primary completion date • Endometrial Cancer • Oncology • Solid Tumor • Uterine Cancer • HER-2 • MSI

AVB-S6-500 and Durvalumab in Treating Patients With Platinum-Resistant or Recurrent Ovarian, Fallopian Tube, or Primary Peritoneal Cancer (clinicaltrials.gov) - P1/2 | N=12 | Active, not recruiting | Sponsor: M.D. Anderson Cancer Center | Trial completion date: Feb 2024 ➔ Feb 2025 | Trial primary completion date: Feb 2024 ➔ Feb 2025

Combination therapy • Trial completion date • Trial primary completion date • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Refractory Ovarian Cancer • Solid Tumor

AVB-S6-500 and Durvalumab in Treating Patients With Platinum-Resistant or Recurrent Ovarian, Fallopian Tube, or Primary Peritoneal Cancer (clinicaltrials.gov) - P1/2 | N=12 | Active, not recruiting | Sponsor: M.D. Anderson Cancer Center | N=19 ➔ 12

Combination therapy • Enrollment change • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Refractory Ovarian Cancer • Solid Tumor

Pipeline Moves: Prospects drop after Phase III ovarian cancer trial failure (Clinical Trials Arena) - "Aravive’s batiraxcept saw its Likelihood of Approval (LoA) for ovarian cancer drop dramatically in ovarian cancer after a Phase III trial was terminated....The trial’s status was updated from active, not recruiting to terminated on ClinicalTrials.gov on 26 October. According to the site, the termination is due to the trial showing no significant differences in median progression free survival (PFS) between batiraxcept and paclitaxel or paclitaxel alone arms."

Trial termination • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor

AVB-500 (Batiraxcept) in Combination With Paclitaxel in Recurrent High Grade Uterine Cancer (clinicaltrials.gov) - P1 | N=36 | Not yet recruiting | Sponsor: Washington University School of Medicine | Trial completion date: Apr 2033 ➔ Aug 2033 | Initiation date: Sep 2023 ➔ Dec 2023 | Trial primary completion date: May 2028 ➔ Aug 2028

Combination therapy • Trial completion date • Trial initiation date • Trial primary completion date • Endometrial Cancer • Oncology • Solid Tumor • Uterine Cancer • GAS6 • HER-2 • MSI

AVB500-RCC-003: Safety and Efficacy Study of AVB-S6-500 (Batiraxcept) in Patients With Advanced or Metastatic Clear Cell Renal Cell Carcinoma (clinicaltrials.gov) - P1b/2 | N=72 | Terminated | Sponsor: Aravive, Inc. | Trial completion date: Mar 2025 ➔ Aug 2023 | Active, not recruiting ➔ Terminated | Trial primary completion date: Dec 2024 ➔ Aug 2023; Due to business reasons

Combination therapy • Metastases • Monotherapy • Trial completion date • Trial primary completion date • Trial termination • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor • GAS6

AVB500-PC-005: Safety and Efficacy Study of AVB-S6-500 (Batiraxcept) in Patients With Advanced Pancreatic Adenocarcinoma (clinicaltrials.gov) - P1b/2 | N=34 | Terminated | Sponsor: Aravive, Inc. | N=99 ➔ 34 | Trial completion date: Oct 2025 ➔ Aug 2023 | Recruiting ➔ Terminated | Trial primary completion date: Oct 2024 ➔ Aug 2023; Due to business reasons

Enrollment change • Metastases • Trial completion date • Trial primary completion date • Trial termination • Gastrointestinal Cancer • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • GAS6

ENGOT OV66: Batiraxcept (AVB-S6-500)/Placebo in Combination With Paclitaxel in Patients With Platinum-Resistant Recurrent Ovarian Cancer (clinicaltrials.gov) - P3 | N=366 | Terminated | Sponsor: Aravive, Inc. | There was no detriment to overall survival. No new safety signals were identified.

Combination therapy • Trial completion date • Trial termination • Oncology • Ovarian Cancer • Solid Tumor