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Re: I thought cereblon CC-92480 would stun at ASH19 but CC-93269 stole the showCC-93269 corresponds to BCMA TCE (T-cell engager) in the slide CELG used to identify expectations for their broad novel therapy product portfolio with current and future patient segments during the 24May2018 Multiple Myeloma (MM) Deep Dive. CC-92480 is still expected to be the best IMiD ever for MM, but ASH2019 is too early to demonstrate the clinical benefit. The following slides from the MM Deep Dive describe this compound: Here is an excerpt about the TCE from the MM Deep Dive: So beyond CAR T cells. I mentioned we have a campaign is not just about a target cell therapy, but it's about targeting this great next generation targeted in myeloma. On the right of the slide, you see that the format of our bi-specific T cell engage or this is a very -- we think a very optimally designed construct and I'll get to that on the next slide. And then on the left, you see the design of the BCMA antibody-drug conjugate we also think isn't an optimal design. The first the T-cell engager has entered clinical trials, the ADC we plan to file the IND in early 2019 . I'm sure the questions will come out. How are you going to position all of these molecules in the treatment of myeloma either across the BCMA campaign or with your emerging cell line portfolio, I'm certain deem going to answer that question. But there are some considerations on maintenance therapy could be considered with an off the shelf program that's simpler concept a CAR T cell fit patients who may not be able to withstand the acute toxicity of cytokine release syndrome and euro toxicity might be considering for one of these other platforms. And similarly, we know that in some patients with high tumor burden the acute toxicity of T-cell therapies are greater, you could think of a cytotoxic agent as indeed bulking therapy to be followed by kind of consolidation with T-cell therapy . These are just initial thoughts. So this slide summarizes what we think is really a state in the art design and the despite specifically selling gauging anybody this came in through an acquisition of a (inaudible) which was a spin-off from Roche. Importantly, it has bi-valent binding to BCMA with high affinity binding, which means that it's not going to get hung up stuff to T cells in the peripheral blood. It will go to the bone marrow and buying tightly to the malignant plasma cells at which point below Infinity anti-CD 3 binding domain will bind to the T-cells in the bone marrow. So this is a way to optimize the efficacy to where the plasma cells were inside without non specifically active T cells in the blood . In addition, that has a FC domain, which improves the half life of the molecule. Many of you're probably aware that some of the first generation T-cell and Gators like blinatumomab [ph[ are very short half life and happiness right continuous infusion this loss field can be administered once a week are perhaps less frequently because of this long half-life. And then it has some important additional mutations in these that's being domains that optimize the manufacturability in the optimal pairing of the light chains in the heavy change, just to improve the ability to make this product. And this slide is coming from the published preclinical manuscript with this T cell engage our platform. And on the right you see an electron micrograph which just shows and malignant plasma cell and being consumed by T-cell by adding in this by specific engaged which taxes the T cell to the tumor cell. And then just win and meaningful referenced on the bottom, you can see the same thing the myeloma cell with down piece out when you put this engage or in system. And on the right you can see when you look at human, the primary myeloma bone around with the resident T cells that are present in that bone marrow when you add been gauging you see this very efficient killing and the human myeloma cells by the T-cells that are present in that on bone marrow aspect. Another interesting aspect of this molecule is that unlike human these cells that don't express BCMA and they're not killed by this engage or primate B cells, do have a low level and be seen expression , and therefore, the elimination of the primate these cells and our studies becomes a very good (inaudible) again of what to expect in terms of target out killing in humans. So, on the right you can see the elimination of primary cells based on their BCMA target expression across escalating doses of that T-cell (inaudible) selling gauge or and it's very rapid in this is analogous to the CAR T cell within 24 hours. You can see elimination of the target positive cells in the (inaudible) and then on the right, in the traditional myeloma xenograft models again you can see, let's say sales grow up to around 500 cubic cm, you get 3 doses and the T cell engage and you get complete elimination of that myeloma xenograft in this model. So very potent, I'd say almost analogous potency to what we had seen with T-cell engages and maybe other than 92480 something that's not commonly seen with any drugs in these myeloma xenograft models. |
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Msg # | Subject | Author | Recs | Date Posted |
816 | Re: I thought cereblon CC-92480 would stun at ASH19 but CC-93269 stole the show | Biotech2050 | 3 | 11/11/2019 2:52:24 AM |