Dr. Michael Har-Noy, founder and CEO of Immunovative Therapies, Ltd., an Israel biotech company, describes the results of a Phase I/II FDA trial in which the proprietary drug AlloStimTM was combined with tumor cryoablation to treat 42 patients with various types of metastatic cancer.
Dr. Michael Har-Noy is preparing to publish these results in a peer-reviewed journal. This trial was undertaken at a subsidiary company facility in Carlsbad, California. Dr. Michael Har-Noy said that forty-two patients with a variety of metastatic cancers were treated. All patients had been heavily pre-treated with chemotherapy and/or radiation and had a life expectancy of 60 days or less. The average patient age was 61 years; 90% had prior surgery, 45% had prior radiation, all had prior chemotherapy. The tumor types were as follows: 14 breast, seven colorectal, three gallbladder, three squamous cell, three ovarian, two pancreas, two sarcoma, two lung, two esophageal, two prostate, and one bladder. Dr. Michael Har-Noy said that these gravely ill patients had an average of 22.2 metastatic lesions, and their average ECOG (Eastern Cooperative Oncology Group) score was 2.2, indicating severe disability. Dr. Michael Har-Noy said that the patients experienced few side effects from the AlloStimTM. The most common adverse reaction was a flu-like syndrome occurring within the first few days after administration. There were no anaphylactic reactions to the drug. The mean survival of the entire group was 163 days – almost three times the expected survival in untreated patients. Remarkably, 20% of the study patients were still in remission fully one year after treatment! Some of the patients went on to live for years after the study. This author does not know the fate or exact longevity of all patients, but as a whole these survival results were far better than anything published to date. Dr. Michael Har-Noy intends to publish these results in a peer-reviewed journal in the near future. He says these results must be interpreted cautiously, as this was only a preliminary study. He is preparing conduct a Phase II/III, randomized double-blind controlled trial of AlloStimTM in metastatic breast cancer patients. Dr. Michael Har-Noy states that the immune mechanism of an allogeneic stem cell transplant has been shown to be effective in killing chemotherapy-resistant metastatic cancer cells despite the presence of immunoavoidance mechanisms, but this immune effect is closely tied to lethal graft versus host disease (GVHD) toxicity, therefore limiting its clinical use.
Dr. Michael Har-Noy has developed a proprietary compound, AlloStimTM, which was designed to elicit a host anti-tumor response without GVHD side effects. Dr. Michael Har-Noy describes how drug was recently evaluated in a FDA-approved phase I/II trial of 42 late-stage metastatic solid tumor patients with a variety of cell types. Most patients in the trial showed evidence of enhanced survival and immune-mediated tumor destruction without GVHD toxicity. Conventional RECIST criteria overestimated tumor size, as responding tumors swelled and appeared larger on computed tomographic scan. Serum interleukin 12 (IL-12) levels were identified as a predictor of enhanced survival. Fifty percent of patients treated with Dr. Michael Har-Noy’s proprietary compound were IL-12 positive and survived a median of 211 days, as opposed to 131 days for those that were IL-12 negative. Nine of 16 refractory metastatic breast cancer patients were IL-12 positive. The Her2 positive subset of breast cancer patients (five of them) were all IL-12 positive and had a median survival of 416 days, while the 11 Her2 negative patients had a median survival of only 134 days Dr. Michael Har-Noy indicates that Her2 positive tumors are usually spread faster and have a worse prognosis than Her2 negative cancers. The superior response to allogeneic cell treatment in theHer2 positive metastatic breast cancer patients may be due to high quantities of anti-Her2 antibodies present in this subset of patients. Hypothetically, the allogeneic cell treatment potentiates the ability of these antibodies to cause tumor destruction. This preliminary report describes a remarkably prolonged survival time in a gravely ill subset of cancer patients with an extremely short life expectancy. Dr. Michael Har-Noy is preparing to conduct a randomized, double-blind Phase II/III study of this unique treatment in metastatic breast cancer patients. Dr. Michael Har-Noy, founder and CEO of Immunovative Therapies, Ltd., describes a case in which a 12-year-old Great Dane presenting with primary bronchoalveolar adenocarcinoma, with a life expectancy no greater than 1 month, survived over 50 weeks post-diagnosis after being treated with a unique chaperone-rich-cell-lysate (CRCL) vaccine.
Prior to treatment by Dr. Michael Har-Noy, the Great Dane presented with ataxia, nystagmus, and hind-end collapse. Chest X-rays showed a nodule in the cranial lobe of the right lung. Ultrasound-guided fine needle biopsy showed bronchoalveolar adenocarcinoma, and the dog underwent thoracotomy and lobectomy. The specimen’s pathology report showed grade III brochoalveolar adenocarcinoma with lymph node metastasis and vascular infiltration. The average survival for this tumor is 6 – 27 days. Using Dr. Michael Har-Noy’s proprietary technology, a 10 gram piece of tumor was incorporated into a CRCL vaccine, which was administered weekly to the Great Dane. Additionally, Imiquimod - a Toll-like receptor 7 (TLR7) agonist - was topically administered to the dog for the first 12 treatments to stimulate local Langerhans cells. Furthermore, a single bacillus Calmette-Guerin (BCG) injection was given at 30 weeks of treatment to further stimulate the dog’s immune response. The Great Dane remained stable and in otherwise good health until it relapsed 44 weeks after the first treatment with Dr. Michael Har-Noy’s CRCL vaccine. The dog then suffered severe gastrointestinal bleeding and was euthanized just after 50 weeks post diagnosis. Dr. Michael Har-Noy says that to his knowledge, this is the first report of significantly improved survival following a diagnosis of grade III/stage III bronchoalveolar adenocarcinoma in a canine patient. This case suggests that the CRCL vaccine combined with topical imiquimod is a safe and very effective treatment for canine cancer. Immunovative Therapies, Ltd. is a biotech company founded in Israel in 2004 by Dr. Michael Har-Noy. Immunovative Therapies, Ltd. manufactures unique compounds that focus on manipulating the immune system to fight cancer. For a new biotech company, developing and marketing new drugs can be an arduous task. The many government regulations that exist in most countries can be very costly and time consuming to comply with. Frequently, small companies don’t survive the startup process because they run out of money before they are able to bring any new products to market.
Sometimes, however, smaller biotech startup companies develop new therapies that are far more innovative than those manufactured by giant multinational corporations. Immunovative Therapies Ltd., an Israel-based biotech company founded by Dr. Michael Har-Noy, has, on a very limited budget, developed remarkable cutting-edge products that may change the way cancer is treated. They may, in the near future, be ready to bring these drugs to market. Adjuvant treatment today for metastatic cancer still relies primarily on chemotherapy and radiation. These therapies are very toxic, causing devastating side effects and dramatically worsening patients’ quality of life. Preliminary work done by Dr. Michael Har-Noy of Immunovative Therapies has shown that immune-based therapy may be far more effective than these treatments and may have comparatively few side effects. Currently, Dr. Michael Har-Noy is developing AlloStimTM, CryostimTM, and AlloVaxTM, which are complex and unique compounds specially designed to “wake up” the body’s immune system and help it attack cancer cells. Preliminary results in a Phase I/II trial have shown remarkable efficacy of these compounds against a wide variety of tumors. Furthermore, these proprietary drugs appear to have minimal toxicity to the patient. Immunovative Therapies has also obtained regulatory approval in Thailand to conduct a double-blind, randomized Phase II/III trial of AlloStimTM in the treatment of metastatic breast cancer. These prototype compounds being tested by Dr. Michael Har-Noy appear to be far more effective in killing metastatic tumors and far less toxic to normal cells than are conventional treatments. They have the potential to create an entire new industry of oncologic therapy. Dr. Michael Har-Noy, founder and CEO of Immunovative Therapies, Ltd., says that the hostile environment for immune cancer treatment development changed on April 29, 2010. On this date, Dendreon’s (DNDN) Provenge® [sipuleucel-T] became FDA approved for the treatment of metastatic castrate-resistant prostate cancer [CRPC]. A randomized clinical trial involving Provenge® demonstrated a 4.1 month survival increase compared to placebo. Dr. Michael Har-Noy says that these positive results rekindled enthusiasm for cancer vaccine research.
The stock shares of Dendreon, which traded below five dollars in March 2009, subsequently rocketed to a value greater than $57 and Dendreon reached a market capitalization of over $7.8 billion. This remarkable achievement, says Dr. Michael Har-Noy, showed the capital markets that the FDA would approve a living cell immunotherapy if a randomized trial showed that it had statistically significant efficacy, even if that efficacy was marginal. Also, Dendreon showed that Medicare would pay for novel and expensive therapies. Medicare approved a $93,000 of reimbursement for Provenge®. However, Dr. Michael Har-Noy says that Provenge®’s commercialization proved to be much more difficult than predicted. On August 3, 2011, Dendreon lowered its revenue guidance for 2011 and predicted only modest growth. Dendreon’s revised estimates not only caused a dramatic drop in its stock price but also put a damper on other companies trying to bring their own cancer vaccines to market. Finally, said Dr. Michael Har-Noy, Dendreon applied for Chapter 11 bankruptcy on November 10, 2014. The poor market performance of Dendreons’s cancer vaccine treatment again raised fear in the investment community. Dr. Michael Har-Noy says that Dendreon’s failure was likely caused by Provenge®’s inscalablilty rather by its marginal effectiveness. Provenge® cannot be mass produced – it must be made dose-by-dose using a complex process involving the patient’s individual tumor. Dr. Michael Har-Noy, founder and CEO of Immunovative Therapies, Ltd., an Israeli technology company, says that bringing new cancer treatments to market involves a long and difficult process. The many rules that exist in most countries are quite costly to navigate. Small firms often don’t survive the startup process because they run out of money befor they can market their new products.
Sometimes, however, smaller companies create new therapies that are far more advanced than those manufactured by large firms. Dr. Michael Har-Noy, has, with limited funds, designed innovative new drugs that may change cancer treatment permanently. These compounds will hopefully be marketed in the not-too-distant future. Adjuvant therapy of cancer consists primarily of chemotherapy and radiation treatments. These therapies are quite toxic, resulting in severe side effects and significantly impairing patients’ quality of life. Preliminary studies done by Dr. Michael Har-Noy have shown that immune therapies are far more effective than traditional treatments and exhibit much less toxicity. Currently, Dr. Michael Har-Noy is working on marketing AlloStimTM, CryoStimTM, and AlloVaxTM, which are proprietary biologic drugs that “wake up” the body’s immune system and assist it in destgroying malignant cells. Preliminary results in of a Phase I/II trial show significant effects of these drugs against many different tumors. Also, these unique compounds apparently have minimal side effects on the patient. Dr. Michael Har-Noy has attained FDA approval in Thailand to begin a randomized Phase II/III trial of AlloStimTM to treat metastatic colon tumors. These unique compounds being created by Dr. Michael Har-Noy seem to be much more efficacious than traditional chemotherapeutic agents. They may spawn an entire new industry in cancer therapy. Dr. Michael Har-Noy is the founder and CEO of Immunovative Therapies, Ltd., a small and very innovative biotechnology firm in Israel. Dr. Michael Har-Noy says that one of the company’s flagship products, AlloVaxTM, has received full regulatory approval for a randomized, Phase I/II clinical trial in patients with recurrent head and neck cancer. This trial will evaluate both the safety and efficacy of this unique, individualized cancer vaccine in this gravely ill patient population that has no standard treatment options left. Dr. Michael Har-Noy says that this trial will be a 52 patient study, with 39 patients in the AlloVaxTM arm and 13 patients in the placebo group. The study will be conducted at the National Cancer Institute of Thailand. A sample of a patient’s tumor will be harvested and sent to Israel for production of the AlloVaxTM vaccine (purified chaperone proteins). The vaccine samples will then be returned to the clinical site for administration to the study patients. Dr. Michael Har-Noy adds that on days zero, seven, and 14, the patients will receive an intradermal vaccine combined with either AlloStimTM or placebo. On day 21, an infusion of either AlloStimTM or placebo will be administered. This process will be repeated for four complete cycles. Dr. Michael Har-Noy says that the patients will be tracked for radiological, pathological and immunological responses, overall survival, and quality of life. Other trials of Immunovative Therapies, Ltd.’s unique biologic compounds are being planned. Dr. Michael Har-Noy says that pivotal Phase II/III trials in metastatic breast cancer and in KRAS gene positive metastatic colon cancer are being designed.
Dr. Michael Har-Noy says that most of the current excitement over cancer immunotherapy is focused on the field of immune checkpoint inhibitors, a class of monoclonal antibodies (MAbs) that inhibit pathways that block the response of T cells to antigens. Checkpoint inhibitors try to overcome mechanisms by which tumors co-opt certain immune checkpoint pathways, and thus resist T cell-mediated antitumor immunity.
Dr. Michael Har-Noy notes that one checkpoint inhibitor, ipilimumab (Medarex/ BMS’s Yervoy) was approved by the FDA for the therapy of melanoma in March 2011, and in the Europe for second line treatment of metastatic melanoma in 2012. Ipilimumab, says Dr. Michael Har-Noy, is a CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) blocking compound that overcomes blockage of the "second signal" that is required in addition to TCR (T cell receptor) recognition of MHC/antigen for the purpose of activating naïve T cells. Dr. Michael Har-Noy notes that in patients with metastatic melanoma, ipilimumab has about a 10% response rate. However, it has a 20-30% rate of serious adverse effects, including autoimmune toxicities in about 10-15% of patients. The adverse effects of ipilimumab can be overcome via treatment with high-dose steroids. Dr. Michael Har-Noy goes on to say that the autoimmune toxicities associated with ipilimumab seem to be due to the fact that the drug targets CTLA-4 on all T cells in the body that express this protein. It is not specific for antitumor T cells. Thus ipilimumab treatment can give rise to autoimmune-related adverse effects in sites other than tumors. Dr. Michael Har-Noy adds that Ipilimumab treatment may also uncover autoreactive T cells via blockage of CTLA-4. Dr. Michael Har-Noy, CEO of Immunovative Therapies, details a case where a 12-year-old Great Dane with primary bronchoalveolar adenocarcinoma and a life expectancy of about 1 month lived over 50 weeks after treatment with Immunovative Therapies, Ltd.’s chaperone-rich-cell-lysate (CRCL) vaccine.
Prior to treatment, Dr. Michael Har-Noy notes that the Great Dane presented with ataxia, nystagmus, and collapse. A nodule in the cranial lobe of the right lung was present on chest X-ray. Ultrasound-guided needle biopsy revealed bronchoalveolar adenocarcinoma, and so thoracotomy and lobectomy was performed. The tumor pathology report indicated grade III bronchoalveolar adenocarcinoma with nodal metastases and vessel infiltration. The average time for this scenario is 6 – 27 days. Using Immunovative Therapies, Ltd.’s unique methods, Dr. Michael Har-Noy said that a 10 gram piece of the animal’s tumor was used to make the CRCL vaccine, which was then injected weekly into the dog. Imiquimod - a Toll-like receptor 7 (TLR7) agonist - was also given to the animal for the first 12 treatments to stimulate the Langerhans cells. Additionally, the Great Dane was given a single bacillus Calmette-Guerin (BCG) injection at 30 weeks to further augment its immune response. Dr. Michael Har-Noy went on to say that the Great Dane remained in relatively good health until the tumor recurred 44 weeks after the first treatment with the CRCL vaccine. The animal then suffered severe gastrointestinal bleeding and had to be euthanized at just over 50 weeks. Dr. Michael Har-Noy notes that this is the first published case of significantly improved outcome of grade III/stage III bronchoalveolar adenocarcinoma in a dog. This case suggests that Immunovative Therapies, Ltd.’s CRCL vaccine is a safe and effective therapy for canine malignancy. Immunovative Therapies, Ltd. is a biotech company founded in Israel in 2004 by Dr. Michael Har-Noy. Immunovative Therapies, Ltd. manufactures unique compounds that focus on manipulating the immune system to fight cancer. Dr. Michael Har-Noy, founder and CEO of Immunovative Therapies, Ltd., says that the immune response of an allogeneic bone marrow transplant very effectively kills chemo-resistant tumor cells despite their immune avoidance mechanisms. However, he notes that this mechanism often precipitates the deadly graft versus host disease (GVHD) and is therefore of limited clinical usefulness.
Dr. Michael Har-Noy of Immunovative Therapies Ltd. has created a unique drug, AlloStimTM, which can elicit a host anti-cancer immune response without GVHD toxicity. Dr. Michael Har-Noy tested AlloStimTM in an FDA-approved phase I/II trial of 42 patients with a variety of late-stage solid metastatic cancers. Most of these demonstrated enhanced survival and immune-mediated cancer elimination without GVHD toxicity. Traditional RECIST scoring methods overestimated tumor size, as responding cancers developed edema and appeared larger when evaluated using computed tomography. Plasma interleukin 12 (IL-12) levels, says Dr. Michael Har-Noy, appeared to be a predictor of improved survival. Fifty percent of patients treated with Immunovative Therapies, Ltd.’s compounds were IL-12 positive and lived a median of 211 days, compared with 131 days for the IL-12 negative subjects. Nine of 16 metastatic breast cancer patients showed IL-12 positivity. The HER2+ subset of 5 patients were all IL-12 positive and survived a median time of 416 days, while the 11 HER2- survived a median time of 134 days Dr. Michael Har-Noy notes that HER2+ tumors are usually more aggressive and have a poorer prognosis than HER2- malignancies. The improved response to AlloStimTM in the HER2+ breast cancer patients might result from high quantities of anti-HER2 antibodies present in their serum. Hypothetically, says Dr. Michael Har-Noy, the AlloStimTM potentiates the ability of these antibodies to kill malignant cells. This preliminary study details a remarkable increase in survival in a group of gravely ill cancer patients with a very short life expectancy. Dr. Michael Har-Noy of Immunovative Therapies, Ltd. will soon conduct a pivotal Phase II/III trial of AlloStimTM in KRAS-gene positive colon cancer patients. |
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