Delving into the Latest Updates on VEGFR2 peptide vaccine(Merck Serono SA) with Synapse

Overview

Basic Info

Drug Type

Shared antigen vaccine, Synthetic peptide vaccine

Synonyms

VEGFR2 peptide vaccine, VEGFR2 specific T cell vaccine, VXM 01

+ [1]

Target

VEGFR2

Mechanism

VEGFR2 antagonists(Vascular endothelial growth factor receptor 2 antagonists)

Therapeutic Areas

NeoplasmsNervous System DiseasesOther Diseases+ [2]

Active Indication

GliomaRecurrent GlioblastomaColorectal Cancer+ [1]

Inactive Indication

colon cancer liver metastasisMetastatic Colorectal CarcinomaSecondary malignant neoplasm of pancreas

Originator Organization

Merck Serono SA

Active Organization

Merck Serono SAMerck KGaA

Vaximm AG

Inactive Organization

China Medical System Holdings Ltd.

Drug Highest PhasePhase 2

First Approval Date-

Regulation-

Gene Sequence

Sequence Code 117962

Target: *****

Their antiangiogenic effects make vascular endothelial growth factor receptor 2 (VEGFR2) inhibitors useful for cancer treatment. However, most of these drugs have unexpected adverse side effects. Here, we show that the novel VEGFR2 inhibitor YLL545 suppressed tumor angiogenesis and growth in triple-negative breast cancer without adverse effects. YLL545 treatment also markedly inhibited proliferation, migration, invasion, and tube formation by human umbilical vascular endothelial cells (HUVECs) in vitro. These effects of YLL545 were equal to or greater than those seen with sorafenib. In addition, YLL545 inhibited VEGF-induced phosphorylation of VEGFR2 and activation of downstream signaling regulators, such as phospho-STAT3 and phospho-ERK1/2, in HUVECs. Embryonic angiogenesis assays in zebrafish and Matrigel plug assays in mice demonstrated that YLL545 inhibits angiogenesis in vivo. YLL545 also inhibited proliferation and induced apoptosis in MDA-MB-231 breast cancer cells both in vitro and in vivo, and 50 mg/kg/d YLL545 inhibited human tumor xenograft growth by more than 50% in BALB/c nude mice. These observations suggest YLL545 is a potentially useful anticancer drug candidate.

31 May 2024·BMB reports

MMPP is a novel VEGFR2 inhibitor that suppresses angiogenesis via VEGFR2/AKT/ERK/NF-κB pathway

Author: Lee, Hee Pom ; Park, Jae-Young ; Shin, Ha Youn ; Yoon, Do-Young ; Kim, Na-Yeon ; Park, Hyo-Min ; Kim, Uijin ; Hong, Jin Tae

Many types of cancer are associated with excessive angiogenesis. Anti-angiogenic treatment is an effective strategy for treating solid cancers. This study aimed to demonstrate the inhibitory effects of (E)-2-methoxy-4-(3-(4-methoxyphenyl) prop-1-en-1-yl) phenol (MMPP) in VEGFA-induced angiogenesis. The results indicated that MMPP effectively suppressed various angiogenic processes, such as cell migration, invasion, tube formation, and sprouting of new vessels in human umbilical vein endothelial cells (HUVECs) and mouse aortic ring. The inhibitory mechanism of MMPP on angiogenesis involves targeting VEGFR2. MMPP showed high binding affinity for the VEGFR2 ATP-binding domain. Additionally, MMPP improved VEGFR2 thermal stability and inhibited VEGFR2 kinase activity, suppressing the downstream VEGFR2/AKT/ERK pathway. MMPP attenuated the activation and nuclear translocation of NF-κB, and it downregulated NF-κB target genes such as VEGFA, VEGFR2, MMP2, and MMP9. Furthermore, conditioned medium from MMPP-treated breast cancer cells effectively inhibited angiogenesis in endothelial cells. These results suggested that MMPP had great promise as a novel VEGFR2 inhibitor with potent anti-angiogenic properties for cancer treatment via VEGFR2/AKT/ERK/NF-κB signaling pathway. [BMB Reports 2024; 57(5): 244-249].

01 Apr 2024·Heliyon

Evaluation of the efficacy and safety of ramucirumab combined with nab-paclitaxel, lobaplatin, and S-1 in neoadjuvant and conversion therapy for advanced gastric cancer: A study protocol of prospective single-center, randomized controlled and open label clinical trial (RNPLS-01)

Article

Author: Wang, Juan ; Li, Mengbin ; Zhao, Yan ; Liu, Shushang ; Wang, Shu ; Wang, Yuhao ; Ma, Yuxuan ; Ji, Gang ; Yang, Jianjun ; Huo, Huade ; Wang, Haoyuan ; Xu, Guanghui ; Li, Haolin ; Peng, Chaosheng

Objective:

Ramucirumab is a VEGFR2 antagonist. The aim of this trial is to evaluate the efficacy and safety of ramucirumab combined with nab-paclitaxel, lobaplatin and S-1 in neoadjuvant and conversion therapy for advanced gastric cancer.

Methods:

and analysis: This study is a prospective single-center, randomized controlled and open label clinical study, enrolling a total of 140 patients with advanced gastric cancer distributed across two distinct cohorts (Cohort A n = 70; Cohort B n = 70). The central focus of the study lies in evaluating the pathological complete response (pCR) of the cancer post-neoadjuvant or conversion therapy. Secondary endpoints encompass the assessment of the R0 resection rate subsequent to the aforementioned therapies, the occurrence of adverse events (AE), progression-free survival (PFS), overall survival (OS), the objective response rate (ORR), the total response rate and its duration, the disease control rate (DCR), and the duration of overall response (DOR).

Ethics:

Ethics approval has been obtained from the Ethics Committee at the First Affiliated Hospital (Xijing Hospital) of Air force Military Medical University (KY20232220-F-1).

Trial registration:

This trial has been registered at the ClinicalTrials.gov: NCT06169410 (registration date: December 5, 2023).

2

News (Medical) associated with VEGFR2 peptide vaccine(Merck Serono SA)

12 Jul 2023

·www.fiercebiotech.com

South Korean biotech group spies US SPAC as route to Nasdaq

The plan is to take the holding company onto the Nasdaq under the new name OSR Biosciences in the fourth quarter. OSR Holdings is the latest biotech business to choose a merger with a special purpose acquisition company (SPAC) as a way to hop onto the public markets. Seoul, South Korea-headquartered OSR is a global healthcare holding company with operations including a pair of subsidiaries in South Korea and Switzerland focused on developing drugs for oncology and osteoarthritis. The company also owns a distributor of medical devices for neurovascular and other diseases and last week announced plans to acquire Landmark BioVentures, another Swiss company that operates four oncology- and immunology-focused biotech ventures in France. The latest announcement will see OSR merge with U.S.-based Bellevue Life Sciences Acquisition. The SPAC went public in February with a $60 million IPO and the goal of finding a suitable healthcare-focused company to join forces with. In OSR, it appears to have found the desired target, and the plan is to take the holding company onto the Nasdaq under the new name OSR Biosciences in the fourth quarter of the year. The only clinical-stage candidate in OSR’s portfolio is VXM01, an immunotherapy in phase 1/2 development by the Swiss-German biotech Vaximm for glioblastoma in combination with Merck KGaA’s Bavencio. Vaximm also has therapies targeting the proteins mesothelin, WT1 and PD-L1 in preclinical development. "We are delighted to identify OSR Holdings as our candidate,” Bellevue Life Sciences Acquisition's CEO Kuk Hyoun Hwang said in a postmarket release yesterday. “OSR Holdings represents a timely investment opportunity working on the development of breakthrough therapies for unmet medical needs." While SPAC deals were a hot ticket for biotechs to go public a couple of years ago, the rush cooled in 2022 as the industry hit tough times. Since then, their use has been more sporadic, with some companies testing the SPAC waters again near the year’s end. This spring also saw a trickle of merger announcements, with Anew Medical, enGene and NKGen Biotech all opting for the blank check route to market.

AcquisitionIPO

02 Oct 2012

·www.biospace.com

VAXIMM Receives Grant to Expand Pipeline of Oral Cancer Vaccines

Basel (Switzerland), Mannheim (Germany), October 2nd, 2012 – VAXIMM AG, a Swiss-German biotech company focusing on cancer vaccines, today announced that its German subsidiary VAXIMM GmbH has been awarded a grant from the leading-edge BioRN cluster “Cell-based and Molecular Medicine” to expand its oral T-cell vaccine technology platform. The cluster competition is a program of Germany´s Federal Ministry of Education and Research (BMBF) to promote top-notch innovation in Germany. VAXIMM’s lead candidate VXM01 is an oral T-cell vaccine, which targets the tumor vasculature. It is currently in Phase I/II clinical evaluation in pancreatic cancer patients at the Heidelberg University Hospital. The funding from the leading-edge cluster program will be used to develop additional cancer vaccines complementary to VXM01, which are based on the same oral T-cell vaccine technology. A second candidate (VXM06), which targets an undisclosed, abundant, tumor-specific antigen, is already in preclinical development. Two further product candidates are at discovery stage. VAXIMM’s oral T-cell vaccine technology has a number of advantages. The platform can easily and rapidly generate new vaccines, including multivalent vaccines. The resulting products combine oral efficacy with safety and excellent tolerability. Moreover, the vaccines do not require a complex manufacturing infrastructure. “We are pleased about the recognition of the potential of our oral T-cell vaccination platform,” said Dr. Heinz Lubenau, General Manager of VAXIMM GmbH. “It allows leveraging our work on VXM01 to add additional products to our promising pipeline.” About VAXIMMs Oral T-cell Vaccine Technology: VAXIMM's oral T-cell vaccine platform is based on an approved, live attenuated bacterial vaccine strain, which has been applied in millions of individuals for prophylactic vaccination, and is safe and well tolerated. To yield its oral T-cell vaccines, this strain is modified to carry the genetic information of a specific target antigen. After oral vaccination with such modified bacteria, patients are mounting a strong specific cellular immune response against the target. So-called killer cells of the immune system are then targeting and destroying the corresponding cancer or cancer-associated cells. As a result, the tumor shrinks, while metastasis formation and growth are inhibited. The scalable platform offers many advantages, such as oral efficacy, good tolerability, and ease and low cost of candidate generation and manufacturing. About VAXIMM: VAXIMM is a privately held, Swiss- and German-based biotech company that is primarily focused on developing active immunotherapies (vaccines) for patients suffering from cancer. Its initial product candidate VXM01 is targeting the tumor vasculature, which is essential for tumors to grow beyond microscopic size. VXM01 has shown impressive anti-tumor activity in numerous animal studies and commenced human clinical trials in 2011. VAXIMM was formed in 2008 as a joint venture of BB Biotech Ventures and Merck KGaA to develop VXM01. Merck Serono Ventures, Sunstone Capital, and BioMedPartners joined as investors in 2010. VAXIMM GmbH is a fully owned subsidiary of VAXIMM AG, located in Mannheim, Germany. For more information, please see Contact: Dr. Heinz Lubenau Tel.: +49 621 8359 687 10 Email: info@vaximm.com Media Inquiries: akampion Dr. Ludger Wess / Ines-Regina Buth Managing Partners info@akampion.com Tel. +49 40 88 16 59 64 Tel. +49 30 23 63 27 68

Vaccine

100 Deals associated with VEGFR2 peptide vaccine(Merck Serono SA)

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Glioblastoma	Phase 2	FR	Vaximm AG	21 Nov 2018
Glioblastoma	Phase 2	DE	Vaximm AG	21 Nov 2018
Glioblastoma	Phase 2	NL	Vaximm AG	21 Nov 2018
Recurrent Glioblastoma	Phase 2	DE	Merck KGaA	21 Nov 2018
Recurrent Glioblastoma	Phase 2	DE	Vaximm AG	21 Nov 2018
Glioma	Phase 2	-	Merck Serono SA	-
colon cancer liver metastasis	Phase 1	DE	Vaximm AG	01 Feb 2016
Metastatic Colorectal Carcinoma	Phase 1	DE	Vaximm AG	01 Feb 2016
Colorectal Cancer	Phase 1	DE	Vaximm AG	01 Feb 2016
Secondary malignant neoplasm of pancreas	Phase 1	DE	Vaximm AG	01 Dec 2011

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03750071 (ASCO2020) Manual	Phase 1/2	Glioblastoma	30	avelumab+VXM01	hbczhswmec(miubvvciut) = twurgesnof rcnzjfhgrs (vzzcarnclh ) View more	Positive	29 May 2020
AACR2019	Not Applicable	-	-	Erlotinib+VEGFR-2 inhibitor	puwomppgax(nkyjvnryeq) = fulalxzhcd ajczizbzww (afundxsbsb )	-	01 Jul 2019
AACR2019	Not Applicable	-	-	Erlotinib alone	puwomppgax(nkyjvnryeq) = iyjbpagkfh ajczizbzww (afundxsbsb )	-	01 Jul 2019
ESMO2018	Not Applicable	Secondary malignant neoplasm of lung	44	Apatinib	msnqoavztd(qndffkqwgy) = AEs greater than degree 2 was seen in 50.0%, including pneumothorax in 11 cases (25.0%) swoacyijtz (jdqopusswy ) View more	Positive	22 Oct 2018
NCT02718443 (ASCO2018) Manual	Phase 1	Glioblastoma	14	VEGFR2 peptide vaccine	sixmfjsoks(gqirbnrhss) = oawyauukmg yaiplbgzfp (waitjmcszf ) View more	Positive	02 Jun 2018
ASCO2016	Phase 1	Pancreatic Cancer	-	VXM01	gdeithkphx(lpcnncrrwj) = Drug-related adverse events preferentially associated with boosting doses of VXM01 were decreases in lymphocyte count (22% vs 0) duriaaovgz (lihqifwssq ) View more	Positive	20 May 2016
ASCO2016	Phase 1	Pancreatic Cancer	-	Placebo		Positive	20 May 2016
ASCO2009	Phase 1	Pancreatic Cancer	18	VEGFR2-epitope peptide	lkriqdfkqb(qjhvzydtok) = cfmgshszff yogdaazwma (bzhqzrdolm ) View more	-	20 May 2009