REGN5458 is a bispecific T-cell engaging antibody aimed at a target called BCMA, which stands for B-cell maturation antigen, which is a molecule on the surface of essentially all plasma cells, including cancer plasma cells, myeloma cells, but also normal plasma cells that are part of the immune system. And one of the attractive things about the BCMA target is that it does not seem to be expressed on almost any other cells in the body, which makes it a really good target for anti-myeloma therapy. REGN5458 is an off-the-shelf therapy, which is a new term that we've had to come up with that applies to almost all the treatments we use for multiple myeloma. But the ones that are not off the shelf are CAR T-cells, which is a different form of immune therapy that needs to be manufactured from each patient's own immune T-cells, which means that for CAR T-cells, there is a step of collecting the T-cells and then a period of manufacturing before they can be given back to the patient, which means that there's a delay in the initiation of the actual therapy. So off-the-shelf immunotherapies are ones that are available to be given to a patient right at the moment that they need it without a lot of preparatory steps. REGN5458 is given as an intravenous infusion weekly for the first 16 doses or four months and then every two weeks, at least in the clinical trials that have been done so far. The initial doses may need to be given in the hospital to observe for any initial side effects, although I think we're still figuring out which of these treatments are going to need to be given in the hospital and which can be given as an outpatient. REGN5458 is generally being given with step-up dosing, which means that for the initial one or two doses, and in this case probably two doses, we give a small dose and then a medium dose before getting to the full dose of the drug. And this is because one of the main symptoms of this is called the cytokine release syndrome, tends to be less severe when you give a smaller dose, and you can get it out of the way at a less severe manifestation if you give a small dose first and then step up the doses over the first couple of doses before reaching the full dose. So we're going to go through the process of giving the first dose of the drug, and then we're going to go through the process of giving the second dose of the drug, and then we're going to go through the process of giving the second dose of the drug before reaching the full dose. The main side effect that we see with all bispecific T-cell engaging antibodies, and definitely for REGN5458, is a condition called cytokine release syndrome. This is a condition that happens when the antibody goes into the body, attaches to myeloma cells and immune T cells turns on the immune T cells and makes them attack the myeloma cells and in that process the T cells release inflammatory hormones called cytokines out into the body. This causes fevers and fatigue as well as sometimes low blood pressure and low oxygen levels and it is pretty much a universal feature of many of our immune therapies and definitely all of our bi-specific T cell engaging antibodies for multiple myeloma. For RegN 5458 it happens in about 40 percent of people but is typically pretty mild so that it doesn't generally make people very sick and happens almost entirely within the first two doses. One of the toxicities that we worry about with bi-specific T cell engaging antibodies and with any immunotherapy for myeloma is neurotoxicity which was not seen at any significant level with RegN 5458. Another side effect that we think about and worry about is immune suppression because as we kill BCMA positive myeloma cells we're also usually killing normal plasma cells that make our normal antibodies which means that most patients who receive treatments like this will end up having very low levels of normal helpful protective antibodies, a condition that we call immune paresis and patients with very low levels of normal antibodies will often need to receive regular infusions of antibodies collected from other people called intravenous immune globulin or IVIG. The need for IVIG with RegN 5458 was not clearly described in the available data so far but we can assume that many patients will need this supportive treatment. When cytokine release syndrome occurs for the most part when it's mild we manage fevers by giving Tylenol or acetaminophen and making sure that patients are staying well hydrated and most people don't need anything beyond that. If the cytokine release syndrome gets a little bit more severe and starts to affect the blood pressure or oxygen levels we typically treat it with an immune suppressive medicine called tocilizumab which blocks one of the cytokines or inflammatory hormones that are released by the T cells and when we give tocilizumab which is given as an intravenous infusion typically in the hospital that usually quickly shuts down the inflammatory reaction of the cytokine release syndrome so that the fevers stop very quickly and people feel better quickly. The data that have been presented so far for RegN 5458 have all been as a single agent or monotherapy but additional trials have already been initiated in which this bispecific T cell engaging antibody is going to be combined with other current effective anti myeloma medications. In the data that have been presented so far for RegN 5458 as a single agent the responses increased as the dose was increased and in the very effective dose ranges of 200 to 800 milligrams the response rate was approximately 75 percent which is a very encouraging initial response rate for a new anti myeloma medication. There are very limited long term data available for RegN 5458 but we do know that at about eight months 90 percent of the people who had an initial response had not yet had any evidence of their myeloma progressing. The current trials that are enrolling are generally enrolling patients with relapsed and refractory multiple myeloma who have been through most of the available effective agents for myeloma and had them either not work or no longer be a good treatment option. RegN 5458 is a bispecific T cell engaging antibody. A bispecific T cell engaging antibody is a new class of anti-cancer therapies that are being explored a lot in multiple myeloma and I think of it as essentially a double-headed antibody where one end of the antibody is engineered to grab on to a target on the surface of the myeloma cell and the other end grabs onto an immune T cell and brings them together so that the immune cell can then attack the multiple myeloma cell. So this is a way of getting your immune system as a patient to attack your cancer and eliminate the cancer cells by guiding the immune cells to attack them.