Elevar Therapeutics, Inc. today announced that a comparative biochemical analysis identified rivoceranib, its lead investigational drug, as the most selective vascular endothelial growth factor receptor 2 (VEGFR-2) inhibitor when compared with other tyrosine kinase inhibitors (TKIs) with known activity against VEGFR-2.
ORLANDO, Fla., April 18, 2023 (GLOBE NEWSWIRE) -- Elevar Therapeutics, Inc., a fully integrated biopharmaceutical company dedicated to elevating treatment experiences and outcomes for patients who have limited or inadequate therapeutic options, today announced that a comparative biochemical analysis identified rivoceranib, its lead investigational drug, as the most selective vascular endothelial growth factor receptor 2 (VEGFR-2) inhibitor when compared with other tyrosine kinase inhibitors (TKIs) with known activity against VEGFR-2.
The results of the analysis were shared today in a poster presentation at the American Association for Cancer Research (AACR) Annual Meeting 2023 in Orlando.
“Though VEGFR-2 is a known target for anti-cancer therapy, clinical use of VEGFR-2 inhibitors has been challenged by limited efficacy and various side effects, potentially due to low selectivity,” said Seong Jang, Elevar’s chief operating officer and the poster’s lead author. “Rivoceranib’s noteworthy selectivity for VEGFR-2 as compared to other TKIs in this biochemical analysis marks a valuable demonstration of its potential as an anti-cancer therapy, as with increased selectivity comes the possibility of more effective VEGFR-2 dosing and diminished toxicity toward unintended targets, both of which are vitally important to the patients who are confronted with disease.”
Elevar is developing rivoceranib, an oral TKI, in combination with camrelizumab, a PD-1 inhibitor, as a treatment option for hepatocellular carcinoma (HCC), the most common type of liver cancer; as a monotherapy treatment option for adenoid cystic carcinoma (ACC); and as mono and combination therapies in other tumor cell types.
For the biochemical analysis, the activity of rivoceranib and 10 U.S. Food and Drug Administration (FDA)-approved TKIs with known activity against VEGFR-2 were compared against a panel of 270 kinases.
Noteworthy results:
- Rivoceranib retains greater overall activity of non-targeted kinases compared with reference inhibitors.
- Substantial differences in overall residual kinase activity were observed across the panel of 270 kinases among the 11 inhibitors. Among all inhibitors profiled, rivoceranib demonstrated the greatest residual kinase activity across the panel of kinases.
- Rivoceranib is the most selective inhibitor of VEGFR-2 kinase activity among the tested inhibitors.
- Rivoceranib demonstrated >95% inhibition of VEGFR-2, with 54.7% to 99.5% inhibition of only five kinases (i.e., FLT1, FLT4, Ret, PDGFR, and Lyn) detected at both rivoceranib concentrations.
- Compared with rivoceranib, all reference inhibitors tested demonstrated activity against a broader array of kinases.
Key conclusions:
- Rivoceranib was identified as the most selective inhibitor of VEGFR-2 in the analysis of the inhibitory profiles of rivoceranib and 10 reference inhibitors against a panel of 270 known kinases.
- Differences in selectivity among compounds with a similar range of VEGFR-2 kinase inhibition potency are clinically relevant, as toxicities associated with available VEGFR-2 inhibitors are thought to be due in part to their inhibitory effects against kinases outside of the VEGFR family.
- With the increased selectivity seen with rivoceranib, more effective targeting of VEGFR-2 may be achieved due to an ability to deliver higher therapeutic doses with fewer off-target toxicities compared to other TKIs.
- This increased ability to reach higher drug concentrations could potentially result in greater anti-tumor efficacy as well as a capacity to achieve adequate concentrations of the drug at sites with limited drug penetration, such as brain metastases.
- Rivoceranib, as the most selective inhibitor of VEGFR-2, represents an attractive option for improved VEGFR-2 targeting in cancer.
In June 2022, Elevar announced at the American Society of Clinical Oncology (ASCO) annual meeting that in its Phase 2 clinical trial (Study RM-202) of rivoceranib monotherapy in patients with progressive recurrent or metastatic ACC, rivoceranib demonstrated clinical effectiveness, as indicated by substantially reduced tumor progression during the six months after rivoceranib treatment compared to the tumor progression during the six months prior to rivoceranib treatment. There are no currently approved therapies for ACC and the trial was the largest to date in ACC to show this level of effectiveness.
Elevar in September 2022 announced during the annual Congress of the European Society for Medical Oncology (ESMO) that in its Phase 3 CARES 310 study, camrelizumab plus rivoceranib significantly prolonged overall survival and progression-free survival, and improved overall response rate versus sorafenib, a standard first-line treatment for unresectable HCC. The company intends to submit a New Drug Application (NDA) and Biologics License Application for the combination to the FDA during the first half of 2023.
To learn more, view Elevar’s AACR poster and visit ElevarTherapeutics.com.
About Rivoceranib
Rivoceranib, a small-molecule tyrosine kinase inhibitor (TKI), is a highly potent inhibitor of vascular endothelial growth factor receptor 2 (VEGFR-2), a primary pathway for tumor angiogenesis. VEGFR-2 inhibition is a clinically validated approach to limit tumor growth and disease progression. Rivoceranib is currently being studied as a monotherapy and in combination with chemotherapy and immunotherapy in various solid tumor indications. Ongoing clinical studies include hepatocellular carcinoma (HCC) (in combination with camrelizumab), gastric cancer (as a monotherapy and in combination with paclitaxel), adenoid cystic carcinoma (as a monotherapy) and colorectal cancer (in combination with Lonsurf®). Rivoceranib was the first TKI approved in gastric cancer in China (November 2014). It is also approved in China as a first-line treatment for unresectable HCC (February 2023). The drug has been studied in more than 6,000 patients worldwide and was well tolerated in clinical trials with a comparable safety profile to other TKIs and VEGF inhibitors. Orphan drug designations have been granted in gastric cancer (U.S., EU and South Korea), in adenoid cystic carcinoma (U.S.) and in HCC (U.S.). Elevar Therapeutics, Inc. holds the global rights (excluding China) to rivoceranib and has partnered for its development and marketing with HLB-LS in South Korea. Rivoceranib, under the name apatinib, is also approved in China for advanced gastric cancer and in second-line advanced HCC by the Chinese-territory license-holder, Hengrui Pharma, under the brand name Aitan®.
About Elevar Therapeutics
Elevar Therapeutics, Inc. is a rapidly growing, fully integrated biopharmaceutical company built on the promise of elevating treatment experiences and outcomes for patients who have limited or inadequate therapeutic options. Elevar’s lead proprietary drug candidates include rivoceranib and paclitaxel micellar (Apealea®). Rivoceranib, under the name apatinib in China, is commercialized by Hengrui Pharma in China and was approved in China as a single agent for the treatment of gastric cancer (2014), a second-line treatment for advanced HCC (2020), and first-line treatment in combination with apatinib for uHCC (2023). It has been granted Orphan Drug Designation in the U.S., Europe and South Korea and has been clinically tested in more than 1,000 patients worldwide in numerous cancer indications. Apealea® is a non-Cremophor EL based formulation of paclitaxel that received marketing authorization by the European Commission in November 2018, making it Europe’s first non-Cremophor EL formulation of paclitaxel approved for use in ovarian cancer. Elevar is headquartered in New Jersey, with offices in Ireland and South Korea. Additional information is available at ElevarTherapeutics.com.
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