0:00
Suspension culture in the orange are the ones which we already have experienced at GMP scale.
0:06
We work a lot for the viral vaccines but also viral vector development also we have quite a lot of experience in the protein antibody industry.
0:17
So where we come in is that we come in already at the phase one development.
0:22
So until the late stage development and also going towards characterization and late stage production, we develop USP process, DSP process, but also we have in house assay development.
0:38
We also produce our own documentation and help also in the filing for the clients.
0:44
I am also joined by my two of my colleagues, Peter Yan and Danielle.
0:47
So if you have further questions about Batavia, you can also contact them in the booth 17 downstairs.
0:53
So Theolytics.
0:55
Theolytics is a biotech company based in Oxford.
0:58
They have pioneered technology to approach the cancer treatment with their phenotypic selectivity approach where they have managed to overcome the challenges associated with preclinical models. They also have this dual mode of action where they attack the cancer associated fibroblast but also underlying cancer cells.
1:25
THEO-260 is the lead candidate which targets the ovarian cancer.
1:30
So this is basically the topic of this presentation, how we collaborated with them and how we enabled them to produce at scale.
1:41
So as I mentioned the THEO-260 they have with their approach; they have generated a nice preclinical data. Again I cannot show that in this presentation.
1:52
But we would be happy to connect with Theolytics if you have further questions about their data and also their approach.
2:02
So where we come in exactly at the early discovery towards the Phase 1.
2:07
So we developed that output that would enable them to produce Phase one material so that they can achieve their goals and further go ahead with their funding and also clinical trials.
2:18
We are also active in phase two to phase 3 in some of the projects where we associated with global health like organisations like CEPI for pandemic-like situations in Africa targeting LASA, Marburg, Ebola kind of projects where we are involved also in the phase one, phase two and also going towards late stage.
2:39
So something about this project, we had a kick off somewhere end of 2022 where we got the information from the client.
2:50
We started our USP development at a DoE scale.
2:52
So that is the shaker flask platform where we establish our process parameters.
2:56
Then we transferred that to a 10 litre suspension bioreactor culture and then further we scaled up to 40 litres for the engineering run and GMP production.
3:06
As I mentioned so the mode is intravenous, so the product that we had to produce had a really concentrated material, so really high titre.
3:18
So we had to make sure that we reach the DS and DP target.
3:22
Again, I cannot mention because of the confidentiality, but those were really high adeno titre we had to achieve for the DS and DP.
3:30
Further in the engineering ground we generated material for the toxicology study and further going towards the GMP to produce basically the phase one clinical trial material.
3:41
In the meantime we produced research and master viral seed and cell banks and also we developed in house assay development for titres and also residuals.
3:52
So as I mentioned we started somewhere end of 2022 and within four quarters we finalised the GMP run.
4:00
So starting from development transferring to a bioreactor suspension culture and 10 litre then scaling up to 40 litre for engineering and reproduce it at the GMP and the both DS and DP has been released early this year.
4:15
So now this can go towards the phase one clinical trial by the client.
4:21
So how we did it for the off stream as I mentioned DoE study, we did a design of experiment to really optimise the cell growth and the infection process that we further transferred to a 10 litre bio reactor process and we could reproduce data as we expected from the Shaker Flask platform.
4:42
And then further we scaled up.
4:44
In the meantime, closely collaborating with the client, we also optimised for the cell growth and infection process that led to 1 log, higher recovery in infectivity output from the harvest in the 40 litre and then we could reproduce than in the GMP.
4:59
So again I cannot show the harvest data, harvest output in the cell growth over time pre and post infection.
5:05
But those data between engineering and GMP were quite reproducible.
5:12
Now for the DSP, again the process is mentioned here in the high level.
5:18
So you basically have a lysis step endonuclease, then you have multistage clarification, you do pre concentrate your product before the purification and then you concentrate to your DS target and finally a sterile filtration.
5:30
So in each step we leveraged our in-house adeno purification knowledge, but also we screened a lot of filters and conditions for the filtration steps, but also during for the concentration and for the purification chromatographic purification.
5:46
So screening monoliths, membranes, columns, resins and conditions.
5:52
And then you produce a DS which goes to a standard DP process to basically produce your DP for clinical trial.
6:02
So I would like to summarise what we did.
6:04
So in 10 litre we first establish a process parameter in a suspension bioreactor culture.
6:11
Then we generated assay reference material for the runs we received, we could manage let's say more than 50% recovery for a multistage purification process for DSP to produce high concentrated adeno 50% by industry standard is quite high.
6:29
We also could manage the same for engineering run for both USP and DSP, we could have a successful scale up and we could also produce material for tox study which was sufficient.
6:40
And the DSP process could cope with the high titre reproduce basically the harvest because of all the optimization.
6:47
And during GMP again, the data for both DS and DP for the viral particles and activity are quite comparable.
6:56
And basically again, everything was in quality and the titre target was achieved and now it is released for the phase one clinical trial.
7:08
So we take pride in this project by leveraging our core principles.
7:12
We are very flexible.
7:13
I mean, no project is smooth sailing.
7:15
I mean customers are also bound by their timelines and budget.
7:18
And we also had to adhere to those timelines and budget.
7:22
But together we could manage all the challenges we faced.
7:26
We had to change cell lines, we had to change few things within the project in the four quarters, but we managed to achieve the target.
7:35
So basically without showing a lot of data due to the confidentiality issue, I would like to summarise that we could develop adeno purification process at scale for then lead candidate THEO-260 targeting the ovarian cancer.
7:52
We could successfully scale up to 40 litre scale generating tox and CTM material and we were first time right in all the stages.
8:02
Yeah, it was a close and intense collaboration.
8:04
But we take pride that we enabled them to go further for their funding grounds and clinical trial.
8:13
That's basically my presentation today.
