1 00:00:01,730 --> 00:00:06,731 - [Dr. Sweeney] My name is Bernie Sweeney and I head up the Cell Expression Center of Excellence 2 00:00:06,731 --> 00:00:10,276 here in the BioR&D organization at Lonza. 3 00:00:10,276 --> 00:00:18,940 It consists of a group of 35 experienced scientists, and our focus is around developing and improving our GS 4 00:00:18,940 --> 00:00:21,550 platform for the future. 5 00:00:21,550 --> 00:00:26,920 So one of the main challenges that we're facing at the moment is that our host cell lines have not been 6 00:00:26,920 --> 00:00:34,175 optimized for the production of more complex molecules that are coming out of our development organizations. 7 00:00:34,175 --> 00:00:40,085 To address this here at Lonza, we are employing gene editing tools, 8 00:00:40,085 --> 00:00:46,225 bioinformatics tools, and high throughput technologies in order to develop 9 00:00:46,225 --> 00:00:48,045 the new host cell lines of the future. 10 00:00:48,045 --> 00:00:49,395 - [Dr. O'Callaghan] My name is Peter O'Callaghan. 11 00:00:49,395 --> 00:00:55,285 I'm head of Expression Systems Sciences working in the licensing team at Lonza based out of Cambridge, UK. 12 00:00:55,285 --> 00:01:00,475 In the licensing team, what we do is we out-license the Lonza technology to our 13 00:01:00,475 --> 00:01:06,305 customers all over the world, and we support them to achieve the best possible outcomes with our platforms. 14 00:01:06,305 --> 00:01:13,255 In terms of the benefits that this new GS Effex® cell line will have to support discovery and manufacturing, 15 00:01:13,255 --> 00:01:18,395 the main one is really that we can support customers in using the cell line going all the way 16 00:01:18,395 --> 00:01:23,715 through from early phase discovery right through to commercial supply of therapeutic proteins 17 00:01:23,715 --> 00:01:24,715 into the market. 18 00:01:24,715 --> 00:01:31,401 And that's because this new cell line slots into the industry standard GS gene expression system at Lonza. 19 00:01:31,401 --> 00:01:37,871 It works with all our system components, our hyperactive piggyBac® transposase enzyme, 20 00:01:37,871 --> 00:01:42,841 our expression vector platform, as well as all our cell line construction workflows. 21 00:01:42,841 --> 00:01:47,571 So what that means is that customers who are discovering and developing new therapies that need 22 00:01:47,571 --> 00:01:54,811 enhanced ADCC, they can use this cell line seamlessly with all our other components and we can support them 23 00:01:54,811 --> 00:01:59,401 in doing that from early-stage discovery work in terms of transient workflows, 24 00:01:59,401 --> 00:02:01,936 stable pool workflows and so on. 25 00:02:01,936 --> 00:02:07,346 And then support them all the way through to commercial manufacturing and supply to the market using this same 26 00:02:07,346 --> 00:02:08,386 set of components. 27 00:02:08,386 --> 00:02:13,506 With this new GS Effex® cell line, you can produce recombinant therapeutic proteins 28 00:02:13,506 --> 00:02:15,676 that have enhanced ADCC. 29 00:02:15,676 --> 00:02:23,006 Traditionally in the market, molecules such as IgG1s typically are used for cancer 30 00:02:23,006 --> 00:02:30,307 immunotherapy and they're often produced and to have or lack fucose on the core N-glycan so that they 31 00:02:30,307 --> 00:02:36,087 have is more potent ADCC activation, which is an important attribute for a therapeutic 32 00:02:36,087 --> 00:02:40,627 protein targeting cancer cells, for example. 33 00:02:40,627 --> 00:02:49,447 So Lonza launched the bYlok® technology back in 2022 and it was targeted to improve our ability to manufacture 34 00:02:49,447 --> 00:02:52,207 complex bi-specific antibodies. 35 00:02:52,207 --> 00:03:00,167 The technology is based on the realization that when you make bi-specific antibodies of the classic IgG and 36 00:03:00,167 --> 00:03:04,466 like format with two different heavy chains and two different light chains, 37 00:03:04,466 --> 00:03:10,106 when you're producing them in a CHO expression platform, you can often get mis-pairing and shuffling 38 00:03:10,106 --> 00:03:12,556 of the heavy and light chains. 39 00:03:12,556 --> 00:03:20,076 So to solve that, Lonza developed the bYlok® technology and it's based on relocating the disulfide bond on one 40 00:03:20,076 --> 00:03:25,456 Fab arm side of the bi-specific antibody and we relocate it from the constant regions into the 41 00:03:25,456 --> 00:03:28,106 interface of the variable regions. 42 00:03:28,106 --> 00:03:34,024 What this new disulfide bond does is help to ensure correct heavy-light chain pairing, 43 00:03:34,024 --> 00:03:35,654 but also help to prevent mis-pairing. 44 00:03:35,654 --> 00:03:41,534 And at Lonza what we do is we combine that technology to solve heavy-light chain mis-pairing in combination 45 00:03:41,534 --> 00:03:45,914 with knobs-into-holes to ensure efficient heavy-chain heterodimerization. 46 00:03:45,914 --> 00:03:52,394 And when you use these platforms in combination, you can get very high rates of full assembly and 47 00:03:52,394 --> 00:03:56,954 bi-specific antibodies, typically about 95% when you use it in combination 48 00:03:56,954 --> 00:03:58,754 with our CHO expression platform. 49 00:03:58,754 --> 00:04:04,070 So we believe it really solves some of the key challenges in making these bi-specific antibodies and 50 00:04:04,070 --> 00:04:05,410 that's why we launched it into the market. 51 00:04:05,410 --> 00:04:12,870 - The advice that I'd give scientists around investing in new technologies for their cell line process is that 52 00:04:12,870 --> 00:04:15,720 you need to continue to invest. 53 00:04:15,720 --> 00:04:24,240 But where I would put the money is around data collection and data interrogation, 54 00:04:24,240 --> 00:04:29,940 because there's a lot we can learn from our current processes that will enable us to build improved 55 00:04:29,940 --> 00:04:31,601 platforms going forward. 56 00:04:31,601 --> 00:04:36,791 How will these impact cell line development programs going forward? 57 00:04:36,791 --> 00:04:43,821 I think if we can utilize and interrogate the data that we currently have and building out our data sets, 58 00:04:43,821 --> 00:04:50,661 we will improve our selection process and also reduce the amount of work required to select the optimal cell 59 00:04:50,661 --> 00:04:54,238 line to take into manufacturing.