R&D Performance

Achieving new drug development through innovative R&D

Achieving new drug development through innovative R&D

Thesis Research Status

GemVax R&D is proceeding the development of therapeutic agents by verifying the efficacy of peptide-based drugs for various indications. It is based on the development technology for telomerase-derived pancreatic cancer immunotherapy.

Conference Presentation on Cancer Immunotherapy

Predictive cytokine biomarkers for survival in patients with advanced pancreatic cancer randomized to sequential chemoimmunotherapy comprising gemcitabine and capecitabine (GemCap) followed by the telomerase vaccine GV1001 compared to concurrent chemoimmunotherapy in the TeloVac phase III trial

In the TeloVac clinical trial, when the baseline eotaxin level (81.02 pg/ml) divided into high and low patient groups, it was reported that the median survival (451 days) in patients with high baseline eotaxin levels was approximately 260 days longer than the median survival (188 days) in patients with low baseline eotaxin levels. This suggests a correlation between baseline eotaxin levels and survival rates.

Presenter : John P. Neoptolemos et al., ASCO Annual Meeting 2014

An exploratory phase I trial of immunochemoradiotherapy in locally advanced and borderline resectable (LA/BR) pancreatic adenocarcinoma (PC)

We discuss the problems of the anticancer immune response of gemcitabine and external beam radiation therapy in patients with locally advanced pancreatic cancer, and report the advantages and immunogenicity of GV1001+adjuvant+PDE-5 inhibitor.

Presenter : Todd S. Crocenzi MD et al., Gastrointestinal Cancers Symposium 2013

A phase III randomized trial of chemoimmunotherapy comprising gemcitabine and capecitabine with or without telomerase vaccine with locally advanced or metastatic pancreatic cancer

In the TeloVac phase 3 clinical trial, it was reported that there was no difference in the OS of the GemCap and GV1001 combination administration group and the sequential administration group compared to the GemCap single administration group as they did not meet the statistical criteria.

Presenter : Middleton GW et al., ASCO Annual Meeting Abstract 2013

Translational studies of the TeloVac Trial: Characterization of the Immune response to GV1001

In the TeloVac phase 3 clinical trial, immune responses by GV1001 and alanine-substituted derivatives were observed in the PBMCs of pancreatic cancer patients treated with GV1001. This suggests that understanding the relationship between the GV1001 peptide sequence and T cell activation will play an important role in the development of novel anticancer vaccines.

Presenter : Victoria Shaw et al., UK NCRI abstract 2010

A randomized phase III study of gemcitabine (G) versus GV1001 in sequential combination with G in patients with unresectable pancreatic cancer (PC)

365 pancreatic cancer patients were divided into gemcitabine-treated group and GV1001+GM-CSF-treated group to compare overall survival. Although the effect of GV1001 could not be observed, further research is suggested.

Presenter : T. Buanes et al., 2009 ASCO Annual Meeting

Treatment of advanced pancreatic cancer patients with a telomerase-peptide vaccine together with gemcitabine: A phase II clinical study

Six patients with pancreatic cancer were divided into GV1001 (0.56 mg) + GM-CSF group and gemcitabine (1000 mg/m²) group to compare toxicity and immunity. It was confirmed that safety was secured in the group treated with GV1001 and an immune response occurred in 58% of patients.

Presenter : Aniruddha Choudhury et al., AACR Annual Meeting abstract 2007

Imiquimod a new adjuvant for telomerase peptide vaccine: A phase I trial in patients with inoperable pancreatic cancer

As a novel adjuvant administered together with GV1001, the possibility of Imiquimod replacing GM-CSF was presented. The immune response and safety were confirmed in 35.7% of patients through DTH assay and T cell proliferation assay.

Presenter : S. L. Bernhardt et al., ASCO Annual Meeting Abstract 2005

A phase I/II study of telomerase peptide vaccination of patients with non-small cell lung cancer

As a phase 1/2 clinical trial targeting 26 patients with non-small cell lung cancer, GV1001 (0.112mg or 0.56mg) and HR2822, an anticancer drug, were co-administered together with GM-CSM. Almost 50% of patients were immune to GV1001 and one patient had a complete tumor response.

Presenter : P. F. Brunsvig et al., ASCO Annual Meeting Abstract (2005)

Immunotherapy Pancreatic Cancer

Gemcitabine and capecitabine with or without telomerase peptide vaccine GV1001 in patients with locally advanced or metastatic pancreatic cancer (TeloVac): an open-label, randomized, phase 3 trial

The safety of GV1001 was re-verified in the TeloVac clinical trial in 1062 patients with locally advanced metastatic pancreatic cancer. It also showed the possibility of combination with chemotherapy and immunotherapy.

Author : Gary Middleton et al., The Lancet Oncology 2014, 8: 829-840

Telomerase peptide vaccination of patients with non-resectable pancreatic cancer: a dose escalating phase I/II study

After administering GV1001 in three doses (0.11mg, 0.56mg, 1.87mg) together with GM-CSF for 10 weeks to patients with unresectable pancreatic cancer, the immune response (sensitive skin reaction, T cell proliferation) was observed. The highest immune response and median survival of 8.6 months in the middle dose group (0.56 mg) of 24 out of 38 patients increased significantly compared to other groups, so this is the basis for the clinically applied dose (0.56 mg) of GV1001 for pancreatic cancer.

Author : Bernhardt SL et al., Br J Cancer. 2006, 11: 1474-82

Telomerase (GV1001) vaccination together with gemcitabine in advanced pancreatic cancer patients

GV1001-specific immune response was confirmed in 10 out of 17 pancreatic cancer patients, suggesting the potential of GV1001 as an immune anticancer agent.

Author : Staff C et al., Int J Oncol. 2014, 3: 1293-303

The effects of gemcitabine and capecitabine combination chemotherapy and of low-dose adjuvant GM-CSF on the levels of myeloid-derived suppressor cells in patients with advanced pancreatic cancer

In the TeloVac clinical trial, it was suggested that GV1001 can increase the patient's immune response by reducing myeloid-derived suppressor cells (MDSCs), thereby improving the cancer-specific immunosuppressive environment.

Author : Nicola E. Annels et al., Cancer Immunol Immunother, 2014, 63: 175–183

Immunobiological effects of gemcitabine and capecitabine combination chemotherapy in advanced pancreatic ductal adenocarcinoma

In the TeloVac study, GM-CSF, IL-6, and C-Reactive Protein (CRP) levels were measured in Serum in the GemCap-administered group. As a result, it was confirmed that apoptosis induced by chemotherapy was not related to increased immunogenicity by GV1001.

Author : Middleton G. et al., Br. J. Cancer, 2016, 11: 510-518

The anti-fibrotic effect of GV1001 combined with gemcitabine on treatment of pancreatic ductal adenocarcinoma

In an animal model transplanted with pancreatic ductal adenocarcinoma cells, the most common of pancreatic cancer, when gemcitabine and GV1001 were administered together, tumor size decreased, apoptosis increased, fibrosis, and TNF-alpha, IL-6, and IL-1beta decreased. We presented evidence that GV1001 could inhibit fibrosis caused by pancreatic ductal adenocarcinoma.

Author : Park JK et al., Oncotarget. 2016, 7(46): 75081-75093

Immunotherapy Non-Small Cell Lung Cancer

Immunological factors influencing clinical outcome in lung cancer patients after telomerase peptide vaccination

In a long-term clinical follow-up of 45 non-small cell lung cancer (NSCLC) patients treated with GV1001, the patient group with a specific immune response (reduction of Treg and MDSC) had a longer survival period, and 6 patients survived until 2015. It was reported that the survival period of patients who showed an immune response specific to GV1001 was 54 months, which was more than 4 times higher than that of patients who did not (13 months).

Author : Hansen GL et al., Cancer Immunol Immunother., 2015, 12: 1609-21

Telomerase peptide vaccination in NSCLC: a phase III trial in stage III patients vaccinated after chemoradiotherapy and an 8-year update on a phase I/II trial

As a result of observing the immune response to GV1001 administration in NSCLC patients who received chemoradiotherapy, 13 out of 26 showed a GV1001-specific immune response, and 4 long-time survivors confirmed a T-cell memory response. It has presented potential as a cancer prevention vaccine.

Author : Brunsvig PF et al., Clin Cancer Res, 2011, 17: 6847

Telomerase peptide vaccination: a phase I/II study in patients with non-small cell lung cancer

Through Phase I/II clinical study targeting NSCLC patients, it was confirmed that GV1001 was safe and caused GV1001-specific immunogenicity.

Author : Brunsvig PF et al., Cancer Immunol Immunother., 2006, 55: 1553-1564

Immunotherapy Melanoma

Vaccination of patients with cutaneous melanoma with telomerase-specific peptides

7 out of 10 skin cancer patients showed an immune response specific to GV1001, and the T cell clone obtained from these patients was confirmed to have the ability to kill target cancer cells, suggesting the potential of GV1001 as an anticancer immunotherapeutic agent.

Author : Hunger RE et al., Cancer Immunol Immunother., 2011, 60: 1553-1564

Telomerase peptide vaccination combined with temozolomide: A clinical trial in stage IV melanoma patients

GV1001 specific immune response was observed in 18 out of 23 skin cancer patients, suggesting the possibility of skin cancer treatment when combined with chemotherapy and GV1001.

Author : Kyte JA et al., Clin Cancer Res. 2011, 13: 4568-80

Immunotherapy HCC/CTCL/CLL/RCC

A phase II open label trial evaluating safety and efficacy of a telomerase peptide vaccination in patients with advanced hepatocellular carcinoma

No immune response specific to GV1001 was observed in hepatocellular carcinoma (HCC), but it suggests additional studies are needed for the combined administration of GV1001 and anticancer drugs.

Author : Greten TF et al., BMC Cancer., 2010, 10: 209

Telomerase-specific GV1001 peptide vaccination fails to include objective tumor response in patients with cutaneous T cell lymphoma

GV1001-specific T cell response was confirmed in 1 out of 6 patients with cutaneous T cell lymphoma (CTCL).

Author : Schlapbach C et al., J. Dermatol. Sci., 2011, 2: 75-83

Telomerase (hTERT 611-626) serves as a tumor antigen in B-cell chronic lymphocytic leukemia and generates spontaneously antileukemic, cytotoxic T cells

Since activation of GV1001-specific cytotoxic T lymphocytes was observed in 6 out of 7 patients with B-cell chronic lymphocytic leukemia (B-CLL) which is 3 times higher than in the Ras peptide-treated group, it presents the possibility of GV1001 as a therapeutic vaccine for B-CLL patients.

Author : Kokhaei P et al., Exp Hematol. 2007, 2: 297-304

GV1001 induces apoptosis by reducing angiogenesis in renal cell carcinoma cells both in vitro and in vivo

GV1001 inhibited the survival, migration, and angiogenesis of renal malignant tumor cells through its modulating action on MMP, TIMP, and HIF-1alpha, and also induced tumor growth inhibition and apoptosis in renal cancer tumor transplantation animal models.

Author : Kim GE et al., Urology. 2018, 113: 129-137

Benign Prostatic Hyperplasia

Signal of GV1001 efficacy

The positive results of the phase 2 clinical trial conducted on patients with benign prostatic hyperplasia suggested that it has the potential to become an effective treatment with increased convenience compared to existing treatments that need to be administered daily.

Author : Thoma C Nat Rev Urol. 2018, Epub ahead of print

A randomised, placebo-controlled, multicentre, Phase 2 clinical trial to evaluate the efficacy and safety of GV1001 in patients with benign prostatic hyperplasia

In a phase 2 clinical trial conducted on patients with benign prostatic hyperplasia, the administration of GV1001 showed improvement in symptom-related indicators and a decrease in prostate volume, and also showed good tolerability.

Author : Moon KT et al., BJU Int. 2018, Epub ahead of print

Potential repositioning of GV1001 as a therapeutic agent for testosterone‑induced benign prostatic hyperplasia

It was confirmed that GV1001 significantly decreased prostate weight and prostate index in an animal model of testosterone-induced prostatic hyperplasia, and had an inhibitory effect on 5α reductase.

Author : Kim KS et al., Int J Mol Med, 2018, 42(4):2260-2268

GV1001 interacts with androgen receptor to inhibit prostate cell proliferation in benign prostatic hyperplasia by regulating expression of molecules related to epithelial-mesenchymal transition.

It was confirmed that GV1001 alleviates prostatic hyperplasia by inhibiting prostate epithelial and stromal cell proliferation, prostate size reduction, PSA reduction, immune cell infiltration and TGF-β-mediated EMT through interaction with AR.

Author : Kim YJ et al., Aging (Albany NY), 2021, 13(3):3202-3217

Degenerative Brain Disease Treatment Alzheimer’s disease

Novel vaccine peptide GV1001 effectively blocks β –amyloid toxicity by mimicking the extra-telomeric functions of human telomerase reverse transcriptase

It has been demonstrated that GV1001 has the effect of inhibiting neuronal cell death caused by beta-amyloid, which is the main cause of Alzheimer's disease.

Author : Park HH et al., Neurobiology of Aging. 2014, 35(6): 1255-1274

Neural stem cells injured by oxidative stress can be rejuvenated by GV1001, a novel peptide, through scavenging free radicals and enhancing survival signals

It was confirmed that GV1001 can increase the survival of neural stem cells by lowering the reactive oxygen species level under oxidative stress, increasing the cell survival signal and decreasing the apoptosis signal.

Author : Park HH et al., Neurotoxicology. 2016, 55: 131-141

Efficacy and safety of GV1001 in patients with moderate-to-severe Alzheimer's disease already receiving donepezil: a phase 2 randomized, double-blind, placebo-controlled, multicenter clinical trial.

As a result of observation after administration of two doses (0.56 mg, 1.12 mg) of GV1001 to moderate-severe Alzheimer's patients, the GV1001 1.12 mg group met the primary endpoint statistically significantly, and safety was verified.

Author : Koh SH et al., Alzheimers Res Ther., 2021, 13(1):66

Anti-inflammatory and cytoprotective effects of GV1001

The anti-inflammatory effect of human telomerase-derived peptide on P.gingivalis lipopolysaccharide-induced inflammatory cytokine production and its mechanism in human dental pulp cells

By confirming the anti-inflammatory activity of GV1001 in lipopolysaccharide (LPS)-induced dental pulp cells (hDPCs), it suggests the potential efficacy of GV1001 in inflammatory diseases.

Author : KO YJ et al., Mediators of Inflammation, 2015, 385127

The anti-inflammatory effect of GV1001 mediated by the downregulation of ENO1-induced pro-inflammatory cytokine production

In an in vitro experiment using peripheral blood mononuclear cells (PBMCs) from rheumatoid arthritis patients, GV1001 inhibits MAPK and NF-kB signaling pathways. This shows that it exhibits anti-inflammatory activity by inhibiting the production of inflammatory cytokines by ENO1 stimulation.

Author : Choi JY et al., Immune Network, 2015, 6: 291-303

Protective effect of peptide GV1001 against renal ischemia-reperfusion injury in mice

Through in vivo experiments, it was confirmed that GV1001 reduces ischemic damage to the kidneys that can occur from kidney transplantation by inhibiting the inflammatory response and apoptosis.

Author : Koo TY et al., Transplantation Proceedings 2014, 46: 1117-1122

Reduction of ischemia–reperfusion injury in a rat lung transplantation model by low-concentration GV1001

It has been proven that when a low dose of GV1001 is used together with the lung preservation solution (Ferfadex) used for lung transplantation, a better prevention effect can be expected due to the anti-inflammatory effect of GV1001.

Author : Chang JY et al., European Journal of Cardio-Thoracic Surgery, 2016, 50(5): 972-979

hTERT peptide fragment GV1001 demonstrates radioprotective and antifibrotic effects through suppression of TGF‑β signaling

Premature aging and fibrosis of keratinocytes and fibroblasts exposed to irradiation were inhibited by GV1001. The same action was verified in an animal model of skin fibrosis, suggesting that the protective action of GV1001 against radiation is due to its inhibitory action on the TGF-beta signaling system.

Author : Chen W et al., BJU Int 2018, Epub ahead of print

Novel peptide vaccine GV1001 rescues hearing in kanamycin/furosemide- treated mice

In an animal model of deafness caused by ototoxic kanamycin and furosemide, it was suggested that GV1001 improved the auditory threshold and suppressed damage to outer hair cells in the cochlea.

Author : Kim SH et al., Front Cell Neurosci. 2018, 12:3

Tracking and protection of transplanted stem cells using a ferrocenecarboxylic acid-conjugated peptide that mimics hTERT

Fe-GV1001 conjugated with MRI contrast agent improved the survival, proliferation, and migration of stem cells under hypoxia. When transplanting Fe-GV1001 permeated neural stem cells and mesenchymal stem cells into the brain in a stroke animal model, MRI images showed that the stem cells were distributed around the cerebral infarction. This suggested the possibility that GV1001 could be used as a stem cell tracer.

Author : Park HH et al., Biomaterials. 2018, 155: 80-91

Protective effects of GV1001 on myocardial ischemia‑reperfusion injury

In an animal model that induces ischemia-reperfusion injury of cardiomyocytes, it was suggested that administration of GV1001 reduced myocardial injury site and intracardiac hemorrhage, apoptosis, inflammatory cytokine, neutrophil infiltration, and myeloperoxidase activity.

Author : Chang JE et al., Mol Med Rep. 2017, 16(5): 7315-7320

GV1001 immunotherapy ameliorates joint inflammation in a murine model of rheumatoid arthritis by modifying collagen-specific T-cell responses and downregulating antigen-presenting cells

In an animal model of rheumatoid arthritis, administration of GV1001 showed improvement in clinical symptoms and histopathological indicators and a decrease in serum IL-6. It has been demonstrated that the secretion of IFN-gamma and IL-6 and the secretion of inflammatory cytokines from monocytes by endotoxin are decreased when splenic T cells are stimulated by collagen.

Author : Chen W et al., BJU Int. 2018, 45: 186-193

Protective effect of telomerase-based 16-mer peptide vaccine (GV1001) on inferior epigastric island skin flap survivability in ischemia-reperfusion injury rat model

In an animal model of ischemia-reperfusion-induced skin slice damage, GV1001 administration showed an increase in the skin slice survival site, inflammatory cytokine and neutrophil infiltration, and a decrease in MDA, suggesting the antioxidant and anti-inflammatory action of GV1001.

Author : Lee YK et al., J Plast Surg Hand Surg. 2017, 51(3): 210-216

Inhibition of HIV-1 reactivation by a telomerase-derived peptide in a HSP90- dependent manner

It was reported that GV1001 inhibits the transcriptional promotion of HIV-1 virus through interaction with heat shock protein 90 (HSP90) and NF-kB inhibition, inhibits intracellular proliferation, and increases cell survival.

Author : Kim H et al., Sci Rep. 2016, 6: 28896

Neuroprotective effects of GV1001 in animal stroke model and neural cells subject to oxygen-glucose deprivation/reperfusion injury

It was confirmed that GV1001 was effective in protecting nerve cells by exhibiting cell proliferation, mitochondrial stabilization, anti-apoptosis, anti-aging, and antioxidant effects in ischemia-reperfusion-injured stroke animal models.

Author : Kwon HS et al., Journal of stroke, 2021, 23(3):420-436

A telomerase-derived peptide exerts an anti-hepatitis B virus effect via mtDNA stress-dependent type I IFN production

It was confirmed that GV1001 exerts antiviral effect against HBV infection through mitochondrial DNA stress-mediated IFN-I production.

Author : Choi YM et al., Frontiers in Immunology, 2020, 11:652

The novel peptide vaccine GV1001 protects hearing in a kanamycin-induced ototoxicity mouse model

In an animal model of ototoxic deafness caused by Kanamycin, GV1001 itself did not have a detrimental effect on internal organs or kidneys, and it was confirmed that GV1001 protected hair cell damage in the cochlea.

Author : Kim SY et al., Otol Neurotol, 2018, 39(8):e731-e737

Outcomes of peptide vaccine GV1001 treatment in a murine model of acute noise-induced hearing loss

It was confirmed that GV1001 was effective in reducing oxidative stress in outer hair cells in an animal model of acute noise-induced hearing loss.

Author : Ja-Won Koo et al., Antioxidants, 2020, 9(2):112

Cell-penetrating Peptide

Tumor-suppressive effect of a telomerase-derived peptide by inhibiting hypoxia-induced HIF-1 a -VEGF signaling axis

In the in vivo xenograft model, it was suggested that GV1001 reduced tumor volume, and that it had an anti-angiogenesis effect through the HIF-1α-VEGF axis as a mechanism of such anticancer and had an anti-tumor effect through HSP70 and HSP90.

Author : Kim BK et al., Biomaterials, 2014, 1-10

Heat shock protein-mediated cell penetration and cytosolic delivery of macromolecules by a telomerase-derived peptide vaccine

The cell-penetrating peptide (CPP) function of GV1001 was confirmed, and thus it was found that GV1001 entered the cell and interacted with HSP90 and HSP70 in the cytoplasm. The cell permeability of GV1001 suggests that it can be used for delivery of various anticancer drugs.

Author : Lee SA et al., Biomaterials, 2013, 34: 7495-7505

The telomerase-derived anticancer peptide vaccine GV1001 as an extracellular heat shock protein-mediated cell-penetrating peptide

GV1001 forms a complex with extracellular heat shock proteins 90 (ehsp90) and 70 (ehsp70) for large substances such as protein, DNA, and siRNA. It has been suggested that there is a role of a cell-penetrating peptide that can deliver these giant substances into cells.

Author : Km H et al., Int J Mol Sci. 2016, 17(12)

Prostate Cancer Treatment

Anti-cancer effect of GV1001 for prostate cancer; function as a ligand of GnRHR

It was confirmed that GV1001 is a GnRHR ligand that inhibits prostate cancer cell metastasis through the Gαs-coupled cAMP signaling pathway. In an animal model transplanted with a prostate cancer cell line, it was confirmed that cancer cell growth was inhibited through the death of tumor cells.

Author : Kim JW et al., Endocr Relat Cancer, 2019, 26(2):147-162

GV1001 inhibits cell viability and induces apoptosis in castration-resistant prostate cancer cells through the AKT-NF-kB-VEGF pathway

By inhibiting the AKT/NF-kB/VEGF mechanism, it was confirmed that GV1001 had the effect of inhibiting angiogenesis, apoptosis induction, and cell viability of prostate cancer cells.

Author : Park YH et al., Journal of Cancer, 2019, 10(25):6269-6277

Anti-metastatic effect of GV1001 on prostate cancer cells; roles of GnRHR-mediated Gas-cAMP pathway and AR-YAP1 axis

GV1001 inhibited the expression of cancer cell metastasis-related genes and inhibited the migration of prostate cancer cells in the splenic liver metastasis mouse model.

Author : Kim JW et al., Cell & Bioscience, 2021, 11(1):191

Choroidal neovascularization

A telomerase-derived peptide vaccine inhibits laser-induced choroidal neovascularization in a rat model

It was confirmed that GV1001 significantly inhibited the development of choroidal neovascularization by regulating NF-kB signal activation and regulating IL-1β, IL-6, and VEGF in an animal model of choroidal neovascularization.

Author : Lee EK et al., Translational research, 2019, 216:30-42

Conlon Cancer Treatment

A phase II study of chemotherapy in combination with telomerase peptide vaccine (GV1001) as second-line treatment in patients with metastatic colorectal cancer

As a result of administering GV1001 in combination with chemotherapy and targeted chemotherapy in patients with recurrent or metastatic colorectal cancer, the disease control rate (primary efficacy endpoint) was 90.9%, and the objective response rate (secondary efficacy endpoint) was 34.1%, and no Progressive survival and overall survival were reported to be 7.1 months and 12.8 months.

Author : Kim SJ et al., Journal of Cancer, 2022, 13(4):1363-1369