Dr. Michael Har-Noy plans tostart a pivotal Phase II/III randomized study of AlloStim TM in the therapyof metastatic KRAS gene positive colon tumors. Dr. Michael Har-Noy notes there is no approved third line treatment forthese patients. A favorable outcome ofthis study would likely lead to FDA marketing approval for AlloStim TM. Dr. Michael Har-Noy intends to start thestudy in the United States as well as two other international sites.
Dr. Michael Har-Noy of Immunovative Therapies, Ltd. says that checkpoint blockade compoiunds block a molecule used by tumor cells to turn off immune cells that are primed and ready to kill. Yervoy blocks the molecule CTLA-4 and Opdivo blocks a molecule named PD-1. When these molecules are neutralized, immune cells can see and kill the cancer cells.
However, Dr. Michael Har-Noy says that these blockade drugs only work if the patient has an intact immune response that can eliminate the cancers. Most cancer patients have an ineffective immune response and for this reason the response rates of checkpoint blockade compounds has been poor and is restricted to cancers, such as melanoma, that are very immunogenic.
Dr. Michael Har-Noy has created an innovative technology that may be effective in treating most types of tumors and infectious diseases. This technology is completely different from previously tested immunotherapies. Instead of being conceptualized first in animals and then in humans, Dr. Michael Har-Noy’s unique platform was reverse engineered from a known human immune response that has already been shown to be capable of eradicating chemotherapy-resistant metastatic tumors and that has been curative in many instances.
The immune reaction resulting from the transplantation of a person’s immune cells (adult stem cells) into a cancer patient has been described as the most potent anti-tumor mechanism ever discovered. Dr. Michael Har-Noy says that this reaction, called the “graft vs. tumor” effect or “GVT”, is the only known mechanism that can, without surgery, debulk chemotherapy-resistant metastatic cancer. However, the clinical utility of the GVT effect is drastically limited due to its often lethal complication called “graft vs. host disease” or “GVHD” which is closely associated with the GVT cascade. The separation of the curative GVT mechanism from the detrimental GVHD effect has been referred to as the “holy grail” of transplantation. Dr. Michael Har-Noy has synthesized a compound called AlloStimTM that uses the proprietary “Mirror EffectTM” technology to mimic the curative effect of a transplant without GVHD toxicity
Dr. Michael Har-Noy, CEO of Immunovative Therapies, a biotech company started in Israel in 2004, says that we are losing the fight against cancer. Dr. Michael Har-Noy indicates that over the past 3 decades, the incidence of cancer has increased markedly, affecting about one out of every three females and one out of every two males.. This means that the present rate of occurrences of new cancer cases is 50% higher in men and 25% higher in women than in the previous generation. The National Cancer Institute predicts that, because of our increasingly elderly population, the number of new malignancy cases will almost double by the year 2050.
Dr. Michael Har-Noy says that despite years of clinical research, decreases in mortality from cancer have been minimal, and significant reductions in death rates are primarily due to decreases in lung cancer deaths secondary to less smoking in the population, and not from real advances in cancer therapies. Also, Dr. Michael Har-Noy notes that the total five-year survival rate of about 50% for all cancer cell types is virtually the same as it was in 1970.
Conventional cancer treatments have extremely negative emotional and physical effects on patients. Many feel that the treatment is worse than the disease. The financial burden that cancer therapies place on our culture is profound. Dr. Michael Har-Noy says that the direct annual cost of cancer therapy has almost quadrupled over the past 20 years. It has grown from about $18 billion in 1985 to $41 billion in 1995, and then to an immense $80 billion in 2005. Dr. Michael Har-Noy adds that in 1999, indirect costs from tax increases, wage losses, reduction in overall productivity secondary to cancer was a staggering $100 billion.
At Immunovative Therapies, Ltd., Dr. Michael Har-Noy synthesizes unique biologic drugs that stimulate one’s own immune system to attack malignant cells. Preliminary results of a Phase I/II trial show remarkable efficacy of these drugs against many different tumor cell types. Pivotal randomized Phase II/III trials of these new therapies are being planned.
Dr. Michael Har-Noy, founder and CEO of Immunotherapies, Ltd., says that in light of the unexpected positive results in patients that had exhausted all treatment options in a previous Phase I/II clinical trial, Immunovative Therpies, Ltd. has received full regulatory approval to advance AlloStimTM to a pivotal Phase II/III licensing trial. Dr. Michael Har-Noy notes that this will be a randomized, double-blind, placebo-controlled clinical trial in patients with advanced metastatic breast cancer. The patients will have been previously treated with a taxane, anthracycline and capecitabine. Her2+ patients will be pre-treated with a Herceptin-containing protocol. Dr. Michael Har-Noy goes on to say that a total of 208 patients will be recruited, with 104 receiving AlloStimTM and 104 receiving a placebo compound. The study will take approximately two years to complete enrollment. The trial will be conducted at the National Cancer Institute of Thailand. Dr. Michael Har-Noy says that the primary end-point will be overall survival (OS). Patients are treated with four intradermal AlloStimTM (or placebo) injections on days zero, four, seven, and ten. On day 14, all patients undergo a cryoablation procedure targeting one metastatic lesion and either AlloStimTM or placebo is then infused into the ablated lesion. On day 17, says Dr. Michael Har-Noy, AlloStimTM or placebo is again injected into the previously ablated lesion. On day 21, an intravenous infusion of AlloStimTM or placebo is again administered. Booster IV infusions of AlloStimTM or placebo are administered again on days 49, 77 and 105. Dr. Michael Har-Noy notes that the study is powered at 80% to detect a 50% or greater difference in OS between the arms at a significance level (alpha) of 0.05. Secondary end-points include Quality of Life and immunological response. If the overall survival in the treatment group is significantly longer than the placebo, says Dr. Michael Har-Noy, these data will be used to support US marketing application under rule 21 CFR 312.120. The data can also be used to support marketing applications in Canada, Japan and the EU.
Dr. Michael Har-Noy, founder and CEO of Immunovative Therapies, Ltd., an Israeli biotechnology company, has developed a unique drug called AlloStimTM. This drug creates an immune tumor-killing response similar to that of a bone marrow transplant but without the deadly graft-vs-host side effect. AlloStimTM has key advantages over CAR-T (chimeric antigen receptor T-cell) therapy, which is being developed by companies such as Kite Pharma, Juno Therapeutics, and Novartis. First, says Dr. Michael Har-Noy, AlloStimTM can be mass produced and is not individualized to each patient’s tumor. CAR-T treatment, however, must be made using each patient’s own unique tumor cells, and is therefore not scaleable.
Dr. Michael Har-Noy notes that preliminary studies of AlloStimTM show that it works against most solid tumors, whereas CAR-T therapy seems to have limited efficacy against such lesions. Furthermore, CAR-T therapy can cause serious side effects, the worst of which is a cytokine release syndrome similar to septic shock. AlloStimTM, says Dr. Michael Har-Noy, causes no serious complications. The most common side effect of AlloStimTM is a flu-like syndrome which lasts a short period.
Dr. Michael Har-Noy is preparing to test AlloStimTM in a pivotal Phase III randomized trial involving patients with refractory metastatic colon cancer. Enrolled patients will be KRAS gene positive and will have exhausted all treatment options. For KRAS gene positive metastatic colon cancer patients, there is no real third-line treatment option. Dr. Michael Har-Noy says that if the preliminary trial results are positive, AlloStimTM may qualify for fast track FDA approval. Once approved for colon cancer, AlloStimTM can be tested in a variety of other indications.
Dr. Michael Har-Noy, CEO of Immunovative Therapies, Ltd., says that the “Mirror EffectTM” is an immune reaction that addresses the problem of uncoupling the curative graft versus tumor (GVT) effect of an allogeneic bone marrow transplant (BMT) from the deadly graft versus host disease (GVHD) side effect.
Dr. Michael Har-Noy says that he solved this problem by designing a T-cell infusion that mimicked the immune cascade caused by the transplanted donor cells but that was controlled by the immune mechanism of the patient. This process, termed the “Mirror EffectTM”, could potentially recreate the curative effect of a BMT without the deadly side effects.
The Mirror EffectTM treatment, says Dr. Michael Har-Noy, reverses the closely linked GVT and GVHD mechanisms that come from the infused bone marrow graft. This effect thus stems from the host rather than from transplanted cells, thus causing a host versus tumor (HVT) response that is closely linked to the benign host versus graft (HVG) rejection. To initiate the Mirror EffectTM, normal T-cells are infused into a cancer patient. These cells then cause the patient’s own immune cells to attack the cancer (HVT effect) and cause an inflammatory reaction which neutralizes the immunoavoidance mechanisms of the cancer.
Dr. Michael Har-Noy indicates that since the HVT mechanism must be linked to a HVG rejection, the patient needs an immune system that is strong enough to reject the donor T-cells. Also, since graft rejection (HVG) is required, the donor cells need to be mismatched to the recipient. This is an immense improvement over allogeneic BMT, where only one third of eligible patients can find an appropriately matched donor.
The Mirror EffectTM therefore involves administration of unmatched cells into a cancer patient who has not been pretreated, so that these foreign cells can be rejected by the patient’s immune system. Dr. Michael Har-Noy says that this HVG mechanism is the “mirror” of the deadly GVHD but is not harmful. The HVG rejection starts the host-mediated tumor destruction (HVT), which is the “mirror” of the GVT mechanism. The “mirror” effect mimics the curative GVT mechanism of BMT while at the same time avoiding the deadly toxicity of GVHD.
Dr. Michael Har-Noy thinks that the “Mirror EffectTM” may start an entirely new field of cancer therapy.
Traditional techniques of cancer therapy, such as surgery, radiation, and chemotherapy, cannot eliminate every metastatic malignant cell in the body. Dr. Michael Har-Noy, founder and CEO of Immunovative Therapies Ltd, an Israeli biotechnology firm, says, however, that the immune system can be manipulated do just that. Dr. Michael Har-Noy indicates that a real cure could result if one could direct a patient’s own immune cells to eradicate malignant tumors.
Dr. Michael Har-Noy of Immunovative Therapies, Ltd. has formulated a proprietary process he which he calls the “Mirror EffectTM. The Mirror EffectTM represents a significant advance in our ability to eliminate cancer cells via the immune system and to neutralize the malignant tumor’s ability to evade this response. The Mirror EffectTM technology may stimulate the creation of a new field of cancer treatment. Dr. Michael Har-Noy says that by properly patenting the Mirror EffectTM, Immunovative Therapies, Ltd. could create a hugely profitable business.
Dr. Michael Har-Noy and his colleagues at Immunovative Therapies, Ltd. are working with their patent lawyers to build a portfolio that protects the entire scope of the Mirror EffectTM and defines its use to guide the immune system to treat some of medicine’s the most difficult conditions. Dr. Michael Har-Noy adds Immunovative Therapies, Ltd.’s patent portfolio will not only protect the company’s products and manufacturing methods but may also create a new industry based on immune manipulation as a medical treatment.
Ultimately, says Dr. Michael Har-Noy, Immunovative Therapies, Ltd.’s patent portfolio will probably change modern cancer treatment. Dr. Michael Har-Noy believes that the potential value of this technology is limitless.