Recent research on the role of the immune cells in the cancer micro-environment has generated many novel concepts for anti-cancer drugs targeting immune cell functions regulating the life and death of cancer cells.
Cancer immunotherapy using immune checkpoint inhibitors, such as the anti-PD-1, anti-PD-L1, and anti-CTLA-4 antibodies, is attracting attention as a novel, highly effective treatment for a wide variety of cancer types. Presently a large number of drugs with this type of mechanism are being developed, and it is expected that cancer immunotherapy with these new drugs will become the standard for cancer treatment within the next five years.
At AskAt our research and development work goes beyond the concept of immune checkpoint inhibition, the mainstay of cancer immunotherapy today. This new approach encompasses the development of drugs based on novel treatment concepts that can pave the way for the next generation of cancer immunotherapy. We have already completed animal studies demonstrating effectiveness in major types of cancer, such as lung, colon, breast, prostate and stomach, and on the immune cells. We are currently preparing for clinical studies in the United States in collaboration with a number of academic institutions.
Autoimmune diseases, such as rheumatoid arthritis, mixed connective tissue disease, ulcerative colitis, and psoriasis, are difficult to treat. The existing drugs for these conditions may have therapeutic efficacy, but they can also have serious side effects, such as liver damage and susceptibility to infection. Recently, an antibody drug targeting IL-23 has been developed, producing remarkable results with some autoimmune diseases in clinical settings. These results notwithstanding, treatment by antibody drugs is expensive, produces significant side effects, and generally become less effective over time due to the production of secondary antibodies. AskAt has, however, demonstrated in animal studies that our EP4 inhibitor, which had been shown to be safe in clinical studies, is just as effective as the IL-23 antibody.
Acute Pain and Cancer Pain
The control of postoperative and posttraumatic pain is essential for improving the quality of life of patients. Sufficient pain control at an early stage can hasten patients’ recovery, improve sleep and appetite, and enable successful return to a normal life.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are mainly used for acute and cancer pain and exhibit strong, temporary analgesic action. However, they do not provide sustained relief and may cause serious gastrointestinal injury. The analgesic action of NSAIDs is not strong enough for postoperative pain or severe pain associated with bone metastasis in cancer. Narcotic analgesics are the treatment of choice in those instances, but their effects vary by individual: it is difficult to ascertain which drug should be used and what dosage should be given. In addition, these drugs have serious side effects, such as vomiting and constipation. There is consequently demand for a strong long-lasting analgesic with fewer side effects, one that could reduce the amount of narcotic analgesic used.
AskAt aims to develop an NSAID that is strong and long lasting but with fewer side effects. Our next generation COX-2 inhibitor, currently under development, has demonstrated strong and long-lasting analgesic action in a clinical trial in the United States.
Neuropathic pain is pain or hypersensitivity resulting from nerve injury or dysfunction that is disproportionate to tissue damage. These conditions, including post-herpetic neuralgia, diabetic neuropathy, and postoperative pain, have varying symptoms but are all marked by persistent and unbearable pain. NSAIDs are not effective in the treatment of neuropathic pain. Currently a number of analgesic drugs, such as a calcium channel antagonist and topical anesthesia, adjuvant analgesics, such as tricyclic antidepressants and antiepileptic drugs, and serotonin and norepinephrine reuptake inhibitors (SNRIs) are used. Their effectiveness and response rate are limited, and they have a high incidence of side effects, such as dizziness, lightheadedness, and somnolence.
AskAt’s COX-2 inhibitor has been shown in animal studies to be highly effective for inflammatory pain and for neuropathic pain. Existing COX-2 inhibitors are believed to be ineffective for neuropathic pain and are not indicated for this condition. Thus, our next-generation COX-2 inhibitor for neuropathic pain represents a new category of drug.
Acetylcholine esterase inhibitors and glutamic acid receptor antagonists are commonly used for the treatment of various cognitive disorders, including Alzheimer’s disease. Although these drugs can temporarily delay the progression of these disorders and mask their symptoms, their effectiveness typically begins to decline six months to one year into treatment. Continued therapy does not produce results. Currently there is no long-term therapy for cognitive dysfunction and no drug on the market that can address the underlying causes of dementia.
Age-related macular degeneration
Age-related macular degeneration (AMD) occurs, when a critical region of the retina, the macula, is damaged or deteriorates, thus causing loss of visual acuity and distortion of central vision. This condition is now considered to be the leading cause of visual disability among adult patients. Intravitreal injection of VEGF antibody is a current, standard therapy for wet age-related macular degeneration (wet-AMD), a type of AMD, and is characterized by choroidal neovascularization with intraretinal or subretinal leakage, hemorrhage, and retinal pigment epithelium detachments. Unmet medical needs remain, however, including limited efficacy, physical and mental distress caused by frequent and long-term intravitreal administration, and high drug and healthcare costs.
AskAt’s COX-2 inhibitor, orally and intravitreally, has been shown in animal studies to be highly effective on choroidal neovascularization. Our next-generation COX-2 inhibitor for wet-AMD therefore represents a new category of drug.