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GemVax & KAEL

GemVax & KAEL is dedicated to healthy lives and improved quality of human life

Pipeline

Pipeline

  • RIAVAX™ inj. was approved by Korea MFDS (Ministry of Food and Drug Safety) as pancreatic cancer immunotherapy on September, 2014.
  • The treatment of the final patient in the phase II BPH clinical trial was completed in October 2016. The results of the trial, confirming both the feasibility of treating benign prostatic hyperplasia and the safety relative to pre-existing solutions, were reported by internationally recognized academic institutions and journals. Based on the results from the phase II clinical trial, GV1001 received IND approval for its phase III clinical trial from the Ministry of Food and Drug Safety in April of 2019. To prove GV1001’s superiority, a phase III BPH clinical trial is currently being conducted at 23 leading hospitals in Korea.
  • Numerous reports have demonstrated that GV1001 has possessed anti-inflammatory, anti-oxidative, and hormone-modulatory functions, leading into potential pleiotropic effects on non-cancer indications such as benign prostatic hyperplasia and Alzheimer's disease. Non-clinical studies are being actively conducted to identify the various and extensive effects of GV1001.
  • The in vitro and in vivo data derived from the non-clinical studies of GV1001 exhibited
    its potential viability as a neurological treatment. The development of therapeutic
    agents with extensive mechanisms of actions that can control various pathological
    mechanisms may provide more success in clinical studies than the development of a
    single mechanism-based therapy. A Phase II clinical trial to assess efficacy and safety of
    GV1001 as a treatment of Alzheimer’s disease is currently being conducted. Additionally, GV1001’s US phase II clinical trial was approved by the FDA in May 2019 to confirm its potential as a treatment for Alzheimer’s disease. The new treatment is expected to be validated and is currently under preparation for the clinical trial in the US.
  • Currently, GemVax R&D and international or domestic hospital and university research teams are making joint efforts to expand the indications of GV1001 using the versatile functions of GV1001. We have been actively developing next-generation immunotherapeutics with novel mechanism of actions for various indications including anti-inflammation, cerebral diseases, urogenital disorders, viral infection, anti-oxidation.
Pancreatic Cancer

RIAVAX™ inj. is a peptide consisting of a 16-amino acid sequence from human telomerase reverse transcriptase(hTERT).

  • Telomerase

    Telomerase is an enzyme which elongates telomeres located at the termini of chromosomes. Telomerase is highly over-expressed in malignant cells compared to normal cells. Activation of telomerase, which elongates telomeres after each cell division, is critical for tumor cell immortalization and cancer cell pathogenesis.Due to its relatively high expression in a broad range of tumor tissues, telomerase is an attractive target for tumor therapy. Several early phase clinical trials of GV1001 immunotherapy have been completed in patients with breast, prostate, hepatocarcinoma (HCC), chronic lymphocytic leukemia (CLL) and lung cancers, where the results are encouraging.Telomerase is considered as a marker of tumor cells, however it is also expressed in some normal tissues. In humans, embryonic stem cells have been found to express telomerase, but in the adults, only few somatic cells have telomerase activity. hTERT is expressed in some normal cells, such as bone marrow stem cells and epithelial cells in colonic crypts. However, telomerase is highly over-expressed in malignant cells compared to the normal cells. The difference is thought to provide the necessary window of opportunity for the immune system to discriminate between tumor cells and normal cells.In 2009, the Nobel Prize in Physiology or Medicine was awarded jointly to Elizabeth H. Blackburn, Carol W. Greider and Jack W. Szostak for the discovery of telomeres and the enzyme telomerase.

  • Telomere

    Telomeres are DNA-protein structures containing DNA repeat units that cap the ends of chromosomes and protect them from degradation and fusing with other chromosomes. In normal cells, the telomeres are shortened by several repeat units after each cell division.In the absence of functional telomeres, chromosomes become highly unstable, which can ultimately be lethal to the cell. One way tumor cells avoid this situation is by turning on the expression of telomerase activity. Thus, immortalization involves the arrest of telomere shortening process, in which telomerase is the key enzyme. Telomerase activity is present in more than 90% of cancer tissues.

  • Sources: Mellman et al. Nature, 2011, 480 (7378):480-9
  • RIAVAX™ inj. - Mechanism of Action

    A foreign peptide (GV1001) is engulfed by antigen presenting cells (APCs). APCs are specialized in initiating immune responses against “foreign” material. Thus, the GV1001 uptaken by the APCs in the skin is processed intracellularly, and the APCs presents the peptide/HLA complexes to the T-cells. Then, the activation of T cells takes place in the lymph nodes. The activated T-cells will circulate in the body to search for tumor cells displaying peptide/HLA complexes identical to the complexes presented to them by the APCs. The cancer cells will be killed when they are detected by the activated T-cells.

Benign Prostatic Hyperplasia

Benign Prostatic Hyperplasia

To evaluate the effect of GV1001 on prostate, in vivo studies were conducted where GV1001 was found to have hormonal modulatory functions. In the course of expanding indication of RIAVAX™inj. currently available on the marketas the immunotherapeutic for pancreatic cancer treatment, further studies were conducted and GV1001 was foundto exert an activity to alleviate BPH symptoms by reducing the prostate size and reducing residual urine volume in the bladder.

The efficacy and safety of treatment with GV1001 on patients with benign prostatic hyperplasia were assessed through the management of a randomized, single-blinded and placebo-controlled phase II clinical trial in a parallel design study.The phase II clinical trial, which was initiated in August 2015 with 161 patients used the internationally recognizedIPSS (International Prostate Symptom Score) as a scale to evaluate the efficacy and all of three groups treated with GV1001 showed 30% improvements in the IPSS compared to the baseline at all evaluation visits. Furthermore, GV1001 was found to bewell-tolerated in the patients treated with GV1001 in the study.

Also, an improvement in prostatic volume, urinary flow, and changes in residual volume were observed in all treatment groups. Through these results, GV1001 was determined to share the safety level of a placebo. It is expected that GV1001 will be administered to benign prostatic hyperplasia patients at a frequency of two or four weeks, increasing compliance of patients compared to current drugs which require daily administration.
Based on the results from the phase II clinical trial, GV1001 received IND approval for its phase III clinical trial from the Ministry of Food and Drug Safety in April of 2019. To prove GV1001’s superiority, a phase III BPH clinical trial is currently being conducted at 23 leading hospitals in Korea.

Mechanism of Action

  • Sources: Aragon-Ching et al. Front Biosci. 2007, 12: 4957-71

    GnRH antagonists (modulation of sex hormone) has been developed for
    BPH therapeutic agents. GV1001 exerts the anti-BPH via the disruption of
    hypothalamic-pituitary-testicular axis, considering the fact that GV1001 binds to
    GnRH receptor. The activation of GnRH receptor demonstrated
    GV1001-specific response on prostate, supporting this mechanism of action.

  • Sources: Kim et al. Toxicol. Lett., 2015, 238:S244

    Meanwhile, the conversion of testosterone to 5-alpha-dihydrotestosterone (DHT)
    is a permissive causal postulate for the development of BPH due to the high
    potency of DHT to induce the enlargement of prostate. Inhibitors of 5-alpha
    reductase (5-AR) are currently prescribed for the treatment of BPH.
    GV1001 demonstrates the activity by inhibiting the expression of 5-AR.
    We found that the m-RNA level of 5-AR was also decreased when treated with
    GV1001. The low level of 5-AR is proposed to be, at least in part, responsible for
    the suppression of enlargement of prostate..

Ph II Domestic Clinical Trial Results

  • The primary efficacy variable was changed from baseline(CFB) in total IPSS at

    weeks 4,8,12,13 and 16. At the evaluation visit(week 13), GV1001 treatment
    Group 1 and 2 showed a statistically significant CFB in IPSS compared with the
    control group. Week 13 of GV1001 implementation exhibited an
    improvement of at least 30% from the baseline.

The result indicates that GV1001 was effective and well tolerated, and may provide potential beneficial effects in patients with BPH. Compared with medical therapies that require daily dosing, the convenient dosing regimen of GV1001 may provide greater patient adherence. Further investigation of these observations will require large-scale clinical evaluation.

Reference : A randomized, placebo-controlled, multicenter, Phase 2 clinical trial to evaluate the efficacy and safety of GV1001 in patients with benign prostatic hyperplasia, BJU Int, 2018

Alzheimer’s Disease

Alzheimer’s Disease

GV1001 has been investigated to evaluate its potential mechanism of action and the studies have indicated thatGV1001 has anti-inflammatory, anti-apoptotic and anti-oxidant effects. In the animal studies, GV1001 demonstrated neuroprotective effects by improving cognitive-behavior symptoms of Alzheimer’s disease by restoring the apoptosis and damage of neural stem cellsinduced by amyloid beta and tau protein.

The in vitro research of GV1001 entails 1) GV1001 inhibits amyloid beta-induced brain cell death, 2) GV1001 reduces the level of reactive oxygen species produced by amyloid-beta, 3) GV1001 prevents amyloid-beta from impeding the proliferation of neural stem cells. Based on these results, the efficacy of GV1001 was evaluated through animal models of the Alzheimer’s disease. (Related article : Park HH et al., Neurobiology of Aging. 2014, 35(6): 1255-1274. Park HH et al., Neurotoxicology. 2016, 55: 131-141)

In the Alzheimer’s disease animal model, GV1001 has 1) significantly reduced the amount of amyloid-beta present, a major contributor to the Alzheimer’s disease, 2) prevented the formation of neurofibrillary tangles (NFT) that occur due to non-ideal changes in the Tau protein, 3) not only inhibited astrogliosis, which occurs due to the activation and increase of astrocytes, but also 4) promoted neurogenesis.

These in vivo research results demonstrate that when GV1001 is administered to patients with the Alzheimer's disease, it regulates the amount of amyloid beta, inhibits the production of neurofibrillary tangles created by the Tau protein, reduces brain cell toxicity and activation of astrocytes.These various activities suggest that GV1001 may play a major role in the recovery and rehabilitation of brain function by increasing neural cell neurogenesis.Based on the results of non-clinical studies, phase II clinical trial to evaluate the efficacy and safety of GV1001 in patients with Alzheimer’s disease is currently being conducted.

The development of therapeutic agents with extensive mechanisms of actions that can control various pathological mechanisms may provide more success in clinical studies than the development of a single mechanism-based therapy. A comprehensive analysis of in vitro and in vivo results supports the potential of GV1001 as an Alzheimer's disease treatment. The patients participated in the various clinical trials previously conducted have exhibited superior safety. The phase II clinical trial is currently being conducted to evaluate the efficacy and safety of GV1001 in patients with Alzheimer’s disease. GV1001 with its various functions and with its expected disease-modifying actions,it has the potential to become a solution to the Alzheimer’s disease.

Additionally, GV1001’s US phase II clinical trial was approved by the FDA in May 2019 to confirm its potential as a treatment for Alzheimer’s disease. The new treatment is expected to be validated and is currently under preparation for the clinical trial in the US.

Mechanism of Action

  • Sources: National Institute of Aging, NIH publication number: 08-3782 (September 2008)

    GV1001 inhibited neurotoxicity, apoptosis and the production of reactive oxygen species in neural stem cells induced by amyloid beta.

  • Sources: National Institute of Aging, NIH publication number: 08-3782 (September 2008)

    In the Alzheimer’s disease animal model, GV1001 was found to improvecognitive and memory functions, to reduce the amounts of amyloid beta and tau proteins and to have neuroprotective effects.