From discovery to clinic: New opportunities for biomarker success

Video Transcript

• 00:00 - 00:16: Really, today it was to have that discussion on what are the challenges that pharma is
• 00:16 - 00:20: facing as they’re looking at their biomarker programs, but actually equally then as they’re
• 00:20 - 00:24: actually pushing that up the clinical value chain, what are the challenges that they are
• 00:24 - 00:29: facing and actually, is there more that the sort of ecosystem that sits around pharma
• 00:29 - 00:33: between CROs, platform developers, research partners, and things like that, that can be
• 00:33 - 00:39: done to help really improve some of those outcomes in helping biomarkers help get therapeutics
• 00:39 - 00:40: to the clinic and things like that.
• 00:40 - 00:46: And so with that sort of brief summary into today’s conversation, I’ll get the panel to
• 00:46 - 00:47: introduce themselves.
• 00:47 - 00:49: So, Will, if I can start with you.
• 00:49 - 00:55: Hi, I’m Will Howarth, I’m the Senior Director of Validation and Technical Quality, so the
• 00:55 - 01:02: antibodies that are produced by my great colleagues in China, the UK, and the US to
• 01:02 - 01:07: make sure that characterization of those antibodies is top-notch, to be able to feed them into
• 01:07 - 01:13: a catalog and into a platform provider such as Pioneer and MSD here, and just make sure
• 01:13 - 01:15: that that quality is up to date.
• 01:15 - 01:16: Thank you.
• 01:16 - 01:17: And Radha?
• 01:17 - 01:22: Yep, I’m Radha Krishnan, I’m a psychologist, I’m the Executive Director and part of the
• 01:23 - 01:30: work with the team to see where we have to take biomarkers and the companion diagnostic,
• 01:30 - 01:34: or is there a need for a companion diagnostic, and all of those components, so very happy
• 01:34 - 01:35: to be here.
• 01:35 - 01:36: Thank you.
• 01:36 - 01:40: And Nadine, who is joining us kindly via Zoom from California.
• 01:40 - 01:46: Hey everyone, my name is Nadine, I’m an Associate Director of Translational Tissue Biomarkers
• 01:46 - 01:47: at Pioneer.
• 01:47 - 01:55: I’ve been at Pioneer Immunotherapeutics for almost 40 years, and I oversee the pre-clinical
• 01:55 - 02:00: tissue biomarker work, as well as the clinical biomarker work for our clinical program that
• 02:00 - 02:05: Alicia probably is going to introduce, and I’m very happy to be here.
• 02:05 - 02:07: Thank you, Nadine.
• 02:07 - 02:12: And finally, Alicia, if you could introduce yourself, and then I think also happy for
• 02:12 - 02:16: you to give the room a bit of a view of Pioneer and the programs that you have at the moment
• 02:16 - 02:17: going into the clinic.
• 02:17 - 02:18: Thank you.
• 02:18 - 02:19: Thank you, Courtney.
• 02:19 - 02:22: Thanks so much for inviting both Nadine and I to be here today.
• 02:22 - 02:24: We really appreciate it.
• 02:24 - 02:25: My name is Alicia Levy.
• 02:25 - 02:28: I’m the Chief Operating Officer at Pioneer Immunotherapeutics.
• 02:28 - 02:33: We’re a California-based clinical stage immuno-oncology company.
• 02:33 - 02:36: We currently have two programs that are in the clinic.
• 02:36 - 02:39: Both are first-in-class novel targets.
• 02:39 - 02:45: The furthest along program is targeting TREM2-positive cells, the TREM2-positive cell depleter.
• 02:46 - 02:51: And then we have a TREM1 agonist program that’s also in the clinic, a few months behind the
• 02:51 - 02:55: TREM2 program, which is currently in dose expansion phase.
• 02:55 - 02:59: And then we have a third program we just unveiled a few weeks ago, actually, that Nadine also
• 02:59 - 03:02: leads on top of all of her biomarker responsibilities.
• 03:02 - 03:06: She’s sort of a superwoman at Pioneer against Marco.
• 03:06 - 03:08: So, yeah.
• 03:08 - 03:11: Thank you so much, Courtney and Abcam, for having us.
• 03:11 - 03:12: Perfect.
• 03:13 - 03:17: And so I think with that, I’ll kind of kick off the first question, and maybe I think
• 03:17 - 03:20: it’s more directed to the team at Pioneer.
• 03:20 - 03:26: But with your TREM2 program, which we have worked with you on the reagent aspect of things
• 03:26 - 03:34: for your biomarker, and it being a first-in-class treatment, I’m curious to know, probably both
• 03:34 - 03:39: commercially and technically, what are some of the challenges that you found as a small,
• 03:39 - 03:44: sort of early-stage startup in this space, thinking about the biomarker program and what
• 03:44 - 03:50: the clinical development pathway for it could be or needs to be for your drug?
• 03:50 - 03:52: Nadine, do you want to start and then I can tag on?
• 03:52 - 03:53: Yeah, sure.
• 03:53 - 03:56: So thanks, Courtney, for that question.
• 03:56 - 04:01: So as you mentioned, it’s a first-in-class program, and we picked TREM2 based on its
• 04:01 - 04:03: high expression on tumors.
• 04:03 - 04:08: And so with that selection, we knew it’s not on normal tissue or circulating blood.
• 04:08 - 04:13: So the biomarker strategy, unfortunately, is not on peripheral biomarkers.
• 04:13 - 04:19: So we really had to look for where it’s expressed in tissues, both for predictive biomarker
• 04:19 - 04:22: or pharmacodynamics to understand the MOA.
• 04:22 - 04:30: And so we really had to look in tissues and make sure we have a reagent to look at biopsies
• 04:30 - 04:34: and tumor tissue, FFPE tumor tissue.
• 04:34 - 04:38: So when I joined Pioneer, the first thing we did was to spend a long time to find a
• 04:38 - 04:43: TREM2 and I TREM2 IHC FFPE-compatible antibody.
• 04:43 - 04:49: And so Abcam, since I started science, was the first place to go because I know you can
• 04:49 - 04:51: generate very good IHC antibodies.
• 04:51 - 04:56: So what we did was to look through all your catalog and even pick things that were not
• 04:56 - 05:01: for IHC and just test all of them using different platforms.
• 05:01 - 05:06: And so we looked and looked and came up with a very good antibody that worked for us.
• 05:06 - 05:12: And for the first time, we were able to see TREM2-positive myeloid cells on FFPE tissues
• 05:12 - 05:16: and we had pathologists identify those.
• 05:16 - 05:18: And so this was very exciting.
• 05:18 - 05:23: And at the same time, we connected with you and started another hybridoma campaign with
• 05:23 - 05:29: Linda Liang, who leads all of those efforts, just to see if we can make a custom-made one.
• 05:29 - 05:34: And we did get good targets, but this commercial one that Alicia can talk about was the most
• 05:34 - 05:36: promising one.
• 05:36 - 05:42: And in a way, it allowed us to screen so many tumor types as one of the strategies for ranking
• 05:42 - 05:43: the tumors.
• 05:43 - 05:48: And now we’re using it on clinical tissues in our capillary labs.
• 05:48 - 05:49: Yeah.
• 05:49 - 05:56: So I think from a commercial and business development perspective, in general, we want
• 05:56 - 05:58: to take all of our risk in the clinic, right?
• 05:58 - 06:02: We don’t want to take risk on, is our antibody going to be available?
• 06:02 - 06:05: Are we going to have to switch to a different antibody?
• 06:05 - 06:09: Not by choice, if we want to develop a companion diagnostic.
• 06:09 - 06:17: And so our next step after a lot of the work that Nadine just described was to do a supply
• 06:17 - 06:22: and license agreement to make sure that we would have access to that antibody as long
• 06:22 - 06:24: as we needed it.
• 06:24 - 06:30: And the ability to do that gave us a lot of confidence in investing our resources, our
• 06:30 - 06:34: time and money in developing the antibody further.
• 06:34 - 06:39: And if we need it to be a companion diagnostic, now we know that it’ll be there.
• 06:39 - 06:45: And I’m curious, Nadine, you made a comment that obviously finding antibodies that worked
• 06:45 - 06:51: in the tissue that you’re looking for and things like that was a challenge.
• 06:51 - 06:57: And doing all of that testing will, I know we do obviously a lot of work and a lot of
• 06:57 - 07:04: characterization, but as we look to these sorts of programs with pharma, from your perspective,
• 07:04 - 07:09: what more is there that can be done to help make sure that people see that there’s kind
• 07:09 - 07:14: of more beyond what they might be able to find in the public domain in regards to information
• 07:14 - 07:17: or how it can be characterized and looking at different applications?
• 07:17 - 07:18: Yeah, thanks.
• 07:19 - 07:23: It’s great to hear that you can pick stuff from the catalog and it’s there, and there’s
• 07:23 - 07:25: a lot of data that sits there.
• 07:25 - 07:28: But there’s a lot of data that sits behind all of that.
• 07:28 - 07:34: There’s a massive characterization that goes through to eventually find that final magic
• 07:34 - 07:36: clone that we like.
• 07:36 - 07:40: But we’ll have tested it already, and we’ve tested it in Western Blot.
• 07:40 - 07:41: We might have failed in Western Blot.
• 07:41 - 07:43: We might have passed it in Western Blot.
• 07:43 - 07:44: That’s the data you see.
• 07:45 - 07:50: And behind all of that single image, which is relatively small on the website, there’s
• 07:50 - 07:56: an entire set of TMA data that’s behind that, and that TMA data in multi-tumor, multi-normal
• 07:56 - 08:03: human species is there, and there’s the accompanying scoring data to go with that.
• 08:03 - 08:09: When we’re partnering with our partners, this data that we can suck out of the limb system
• 08:09 - 08:14: we can provide, so we’ve got all of the stuff, whether it’s passed or it’s failed.
• 08:14 - 08:18: It’s the kind of thing that we wouldn’t necessarily put all of it on the website, but
• 08:18 - 08:21: it’s there.
• 08:21 - 08:25: And where possible, if we’ve got the image, we’re very happy to share that kind of thing
• 08:25 - 08:22: as well.
• 08:22 - 08:25: So it’s that, but then there’s the extension of that.
• 08:25 - 08:30: So where we’ve got particular markers, we’ve got the toolbox to extend that.
• 08:30 - 08:34: Whether we then look at sequence liabilities in a particular clone that’s of interest,
• 08:35 - 08:41: or we extend that into further sensitivity checks beyond the 17 different cancer types.
• 08:41 - 08:46: We might take a single cancer type and do a TMA of 60 plus tissues.
• 08:46 - 08:53: We can add that kind of thing on for particular targets because it’s relevant and it helps
• 08:53 - 08:57: to make sure that the relationship is built.
• 08:57 - 09:05: Equally, adding knockout cell pellets where it’s not been done before is an equally important
• 09:05 - 09:10: part where we can bolt things on if they’re not already available.
• 09:10 - 09:16: I think we’ve come across that where we’ve found that the information is not always available
• 09:16 - 09:17: from the domain.
• 09:17 - 09:21: But one good thing is we’ve worked with that kind of number of clients as well.
• 09:21 - 09:26: It’s always very useful to call them up and connect and find out.
• 09:26 - 09:30: And they’re having some of the antibodies that are, you know, you want to use a single
• 09:30 - 09:32: lot and there’s not much available.
• 09:32 - 09:33: There’s very limited stock.
• 09:33 - 09:37: And then we start talking about it and they say, okay, if it’s a critical antibody that
• 09:37 - 09:41: you’re validating and you want it for a particular study, then it’s sort of kept aside.
• 09:41 - 09:45: So there are a lot of things that we have been able to help as well as creating cell
• 09:45 - 09:48: lines, which has been very critical, particularly in the startup of the validation.
• 09:48 - 09:50: You do not know how it works on the turnout.
• 09:51 - 09:56: Or having the TMAs, multi-tissue TMAs or multi-tumor has always been very helpful.
• 09:56 - 10:00: So that interaction and collaboration has actually been very, very helpful.
• 10:00 - 10:05: I think we’ve had very good partnerships from that perspective as well.
• 10:05 - 10:10: And I’m curious, Radha, from, we were talking earlier, you know, maybe the difference between
• 10:10 - 10:16: Pioneer being in that very early stage and kind of finding their way through this kind
• 10:16 - 10:21: of path because they haven’t done it before and maybe haven’t had as much experience.
• 10:21 - 10:25: How does it sort of get approached at Merck?
• 10:25 - 10:29: How do you think about these things and do you tend to try and look internally or again,
• 10:29 - 10:35: how do you look at working with partners or, you know, is the solution driven from what
• 10:35 - 10:40: you can do internally or actually is there also an ambition to look outside and see what
• 10:40 - 10:43: else is available to help support your programs as well?
• 10:43 - 10:46: We start internally and then we see what is available.
• 10:46 - 10:51: But in parallel, we don’t stop at that because we know that there’s going to be so much of
• 10:51 - 10:53: external information available.
• 10:53 - 10:58: And at the end of the day, if you want to go down a CDX route, you want to start early.
• 10:58 - 11:02: You don’t want to be waiting to say I have everything internally done and then suddenly
• 11:02 - 11:06: realize it has to go into a CDX route and I don’t have a partner selected.
• 11:06 - 11:11: Or even knowing that a partner can be done or if there’s anybody can be, you know, scalable
• 11:12 - 11:15: and it’s robust, so we wouldn’t wait too long.
• 11:15 - 11:19: So when we know that there’s some data that looks promising, then we start definitely
• 11:19 - 11:23: speaking to our partner, even as early as the early validation stages.
• 11:23 - 11:28: We’re not going to be waiting until the whole data is coming through.
• 11:28 - 11:33: And I guess, you know, thinking about the fact that you don’t want to get caught out
• 11:33 - 11:38: at a late stage, how do you try and think about mitigating those risks?
• 11:38 - 11:42: Maybe, you know, and thinking about it from a large organization compared to a smaller
• 11:42 - 11:46: organization, I know we’ve had conversations previously as well, Alicia, around kind of
• 11:46 - 11:50: every day you’re burning cash in maybe a different way compared to Merck.
• 11:50 - 11:55: But, you know, how do you think about that risk mitigation and what those programs look
• 11:55 - 12:00: like and try and infuse some of that learning either from your past experiences or again
• 12:00 - 12:05: from looking at other conversations and dialogues externally?
• 12:05 - 12:11: Well, for us, I think because we’ve been doing this for some time, we do look at what
• 12:11 - 12:13: we have in our past.
• 12:13 - 12:14: We do learn from our lessons.
• 12:14 - 12:19: We try learning from our lessons of what has happened and proactively try and see what
• 12:19 - 12:23: we could mitigate or proactively start working and saying, you know, what has worked well
• 12:23 - 12:28: in the past and you know what has not worked well, so try and see where we need to start
• 12:28 - 12:32: putting in our lot of efforts to say that there are things that are not going to work
• 12:32 - 12:36: well to start working with your partners well ahead of time.
• 12:36 - 12:38: And again, it’s time that’s critical.
• 12:38 - 12:43: So, you know, sometimes everything is based upon, you know, driven by science and by data
• 12:43 - 12:48: and clinical correlation of the clinical study teams to say, is that what they need and is
• 12:48 - 12:50: the data good enough and strong enough?
• 12:50 - 12:55: And then working with partners like yourselves to say, so where are we in the phase of the
• 12:55 - 12:57: development?
• 12:57 - 12:59: How quickly should we scale up?
• 12:59 - 13:03: And then, like I was telling you earlier, bringing in the CRO into this whole space,
• 13:03 - 13:06: are we going to be running it as a clinical trial with the CRO or is it going to be academic
• 13:06 - 13:07: based?
• 13:07 - 13:08: Or what is it?
• 13:08 - 13:12: Because everybody has to have that level of time and effort to be able to move up.
• 13:12 - 13:15: So, you know, starting early is the most critical piece.
• 13:15 - 13:18: Setting up the collaboration of the partners is very important.
• 13:18 - 13:22: We need diagnostic partners like yourselves or we need CROs who are going to be our partners
• 13:22 - 13:27: to say that, you know, give them a heads up early on, you know, that things may happen
• 13:27 - 13:32: and once we know that the ball is rolling, you know, people have to be nimble to say,
• 13:32 - 13:36: okay, now I need to start, you know, move quickly because that’s when it starts coming
• 13:36 - 13:37: in.
• 13:37 - 13:40: And by the time all the jigsaw puzzle fits in, we don’t have much time.
• 13:40 - 13:42: And from Pioneer’s perspective, Alicia?
• 13:42 - 13:43: Yeah.
• 13:43 - 13:46: No, I think, you know, we had a venture-backed startup.
• 13:46 - 13:49: There’s very little room for error.
• 13:49 - 13:54: So, you know, we’re always trying to plan for every scenario.
• 13:54 - 13:57: So, you know, is the catalog antibody going to work?
• 13:57 - 13:59: Are there liabilities with the antibody?
• 13:59 - 14:01: Should we be iterating on it?
• 14:01 - 14:05: Should we be working together to think about ways to mitigate some potential risks?
• 14:05 - 14:10: All of those things have to kind of move along in parallel because the last thing that we
• 14:10 - 14:17: can really, you know, tolerate is having to delay the initiation of a next clinical trial
• 14:17 - 14:20: because our diagnostic isn’t ready yet.
• 14:20 - 14:26: So having all of those, you know, pieces kind of going in parallel is very critical.
• 14:26 - 14:31: And I guess I would add, I’m sure Nadine can add more from the technical side, but, you
• 14:31 - 14:37: know, we’re a company of, you know, 65 people and nobody at our company has developed a
• 14:37 - 14:39: companion diagnostic before.
• 14:39 - 14:46: So, you know, we leverage consultants, we leverage our own expertise, and then we also
• 14:47 - 14:52: leveraged, you know, Abcam’s expertise as well when thinking about what our long-term
• 14:52 - 14:54: strategy was going to be.
• 14:54 - 14:59: So, you know, we had discussions a lot when we were doing our manufacturing and license
• 14:59 - 15:04: agreement about, okay, well, how does this agreement that we’re putting together going
• 15:04 - 15:09: to serve us long-term and what do those next agreements look like?
• 15:09 - 15:13: I know those were questions that I had being on the, you know, the person that’s
• 15:13 - 15:14: negotiating the agreements.
• 15:14 - 15:16: How are we, how are these all going to line up?
• 15:16 - 15:20: I don’t want to put something in place today that’s going to cause a problem for me
• 15:20 - 15:21: later.
• 15:21 - 15:26: And, you know, and then down the line I have to have, you know, licenses and, you know,
• 15:26 - 15:29: from our academic partners as well, making sure all of those go together.
• 15:29 - 15:30: Yeah.
• 15:30 - 15:34: That wasn’t just, if I remember, it wasn’t just at a high level of also technical teams
• 15:34 - 15:35: talking to technical teams.
• 15:35 - 15:36: Oh, yeah.
• 15:36 - 15:38: And then that’s all, oh, absolutely.
• 15:38 - 15:39: Flesh out pieces like that.
• 15:39 - 15:41: And I think that’s the beauty of that partnership.
• 15:41 - 15:42: Yeah.
• 15:42 - 15:46: Bringing teams together that can help, you know, where we’ve got an expertise in an
• 15:46 - 15:51: area that you might have less expertise and we can help to guide in that process.
• 15:51 - 15:52: Yeah, absolutely.
• 15:52 - 15:54: I think Nadine can probably speak a lot more.
• 15:54 - 15:56: Yeah.
• 15:56 - 16:00: As you mentioned at the beginning, we had consultants just because we are filing an
• 16:00 - 16:06: investigation and device exemption originally just to see if we will have to select patients
• 16:06 - 16:11: one day based on an IHC cutoff for TREM2, then what would that application be?
• 16:11 - 16:15: And then the first thing we realized about the antibody, how important it is to make
• 16:15 - 16:22: sure the antibody source is secure if we change lots because there’s no more of one lot.
• 16:22 - 16:27: There’s an assay for lot-to-lot variation that technically Abcam being the manufacturing
• 16:27 - 16:31: can provide kind of similar, you know, good quality antibodies.
• 16:32 - 16:38: As well, of course, it becomes clear expiration dates that needs to be a part of that
• 16:38 - 16:39: application for the FDA.
• 16:39 - 16:45: Then we started, of course, those discussion about how does Abcam put an expiration date
• 16:45 - 16:50: for, you know, probably not only IHC purposes, but how can we work together to make
• 16:50 - 16:58: sure expiration and storage that could be really made for the IHC assay to perform really well.
• 16:59 - 17:08: So this is one of the challenges we realized that, oh, you know, we have to work with Abcam
• 17:08 - 17:14: and kind of collaborate on ways to handle the storage, maybe formulation one day, like
• 17:14 - 17:17: Alicia mentioned, to look at the sequence, hotspot, any liability.
• 17:17 - 17:22: Because down the line, if it goes in a CDX, we need to make sure we can store it for longer
• 17:22 - 17:24: terms.
• 17:24 - 17:29: So we did lots of that together, and maybe those are some of the technical challenges,
• 17:29 - 17:31: I would say.
• 17:31 - 17:40: And I’m curious, probably for both Merck and Pioneer, you know, regardless of even these
• 17:40 - 17:45: specific programs, but in your experience, as you’ve been, you know, working on biomarker
• 17:45 - 17:50: programs over time, and, you know, with people in the room who maybe have or haven’t gone
• 17:50 - 17:55: through all the way through to developing CDXs and things, what have you found almost
• 17:55 - 18:01: as the, from that learning, what has been maybe one of the, or some of the more unexpected
• 18:01 - 18:05: challenges that you face, both technically and maybe even commercially that you just,
• 18:05 - 18:09: you know, hopefully that no one’s experience or no one’s thinking could have got you there
• 18:09 - 18:14: that actually maybe if you were working with other partners or you were able to, you know,
• 18:14 - 18:17 collect information elsewhere in different ways could have been helpful.
• 18:17 - 18:21: But has there ever been an experience in these programs that you’ve been looking at
• 18:21 - 18:26: that has just led you to that, like, oh, I couldn’t have ever hoped for that.
• 18:26 - 18:30: But now that I know, you know, to your point, Radha, it’s a learning piece, and you get
• 18:30 - 18:34: to learn it elsewhere, and is there information that you would kind of impart to people as
• 18:34 - 18:38: they’re starting to, you know, go through as an early stage biotech and things like
• 18:38 - 18:40: that?
• 18:40 - 18:45: Yeah, I think technically, I guess it’s not going to be very different because of
• 18:45 - 18:48: the development of antibody and everything is very similar.
• 18:48 - 18:53: But I guess from an IVD perspective, you may want to start thinking if it’s your IFU and
• 18:53 - 18:58: what goes into the IFU, because there are so many differences between different countries
• 18:58 - 19:02: that the amount of validation that you would need for each of these countries are different.
• 19:02 - 19:04: With Germany, it was different.
• 19:04 - 19:06: With China, it’s different.
• 19:06 - 19:08: In Japan, you have your own way of doing things.
• 19:08 - 19:14: So we have seen that some of those was not expected, particularly in Japan and Nagoya.
• 19:14 - 19:18: The type of validation, the type of data that was expected to be provided was a bit
• 19:18 - 19:20: different from everything else.
• 19:20 - 19:22: It was a little bit unexpected when we went there.
• 19:22 - 19:24: It was well-invented.
• 19:24 - 19:27: But then when we came back, we said, it’s the next study that you’re doing,
• 19:27 - 19:29: you know, that you have to be a little bit more prepared.
• 19:29 - 19:33: And a couple of things we had to think out of the box at the moment and have those.
• 19:33 - 19:39: But having those discussions with our diagnostic partners and having those ongoing
• 19:39 - 19:43: discussions with the regulators is extremely important, because that’s when it starts
• 19:43 - 19:47: building up into what you expect or do not expect.
• 19:47 - 19:52: So sometimes you just do not expect that these will come to play.
• 19:52 - 19:56: And of course, the other phase is that you start off thinking that if it’s an IHC marker
• 19:56 - 20:00: that a particular cutoff is going to work well, then halfway you start seeing that that
• 20:00 - 20:03: is really not working well and you have to rethink.
• 20:03 - 20:05: And do we have to do a bridging?
• 20:05 - 20:08: Do we have to do – you know, those are the components that may come up.
• 20:08 - 20:11: It’s not coming as a total surprise, but that has happened.
• 20:11 - 20:13: So, you know, you can only be that much prepared.
• 20:13 - 20:16: There are going to be things that will come around.
• 20:16 - 20:19: And it turns around and you see that all these things are there.
• 20:19 - 20:23: And you could say that, you know, learning from your experience and say, OK, these are
• 20:23 - 20:27: the things you need to start thinking of and putting into place as mitigation strategies.
• 20:27 - 20:33: But, yeah, that’s all that you could do is start thinking around the technical components
• 20:33 - 20:36: and regulatory piece and all of those things.
• 20:36 - 20:38: You can only think forward to a certain point.
• 20:38 - 20:39: Yeah.
• 20:39 - 20:43: And from Pioneer’s perspective, from maybe a technical and looking at your biomarker
• 20:43 - 20:48: programs, Nadine, has there been anything that you think, oh, I couldn’t have hoped
• 20:48 - 20:52: for that, but actually, again, is there sort of a learning and a thought that you think,
• 20:52 - 20:57 that, oh, actually, if I knew that, it would have been really valuable to Radha’s point to
• 20:57 - 21:01: maybe look out for, even though it might not end up being an eventuality?
• 21:02 - 21:03: Yeah.
• 21:03 - 21:07: You know, for me, that’s just technically maybe like the stability and storage for me
• 21:07 - 21:12: were a big thing that I learned, right, that, you know, if you want to transfer to a cap
• 21:12 - 21:17: CLIA lab and potentially CDX, there are a few things, you know, like I mentioned, storage
• 21:17 - 21:23: stability over time, expiration date with some accelerated stress conditions that we
• 21:23 - 21:24: can do.
• 21:24 - 21:29: So these things I’m learning that maybe early on we need to make sure we understand them.
• 21:29 - 21:34: But also I know for a CDX, Abcam manufactures and show cell line, for example, down the
• 21:34 - 21:40: line, while early on it’s in 2R3T cells and that might create just, you know, it’s a different
• 21:40 - 21:43: way to manufacture antibodies.
• 21:43 - 21:50: And so there’s a whole lot of, I would say, screening and, you know, quality checks and
• 21:50 - 21:55: QC for that antibody itself with different condition.
• 21:55 - 22:02: HPLC, SEC, different types, just to understand first that it’s a clean, not degraded antibody
• 22:02 - 22:03: that could be used.
• 22:03 - 22:08: And then, of course, there’s the IHC portion of stability and different ways of looking
• 22:08 - 22:10: at the performance of the assay.
• 22:14 - 22:18: And then one of the things that came up, we were talking about it a bit earlier and actually
• 22:18 - 22:23: we were just having, there was a conversation as we were getting ready to start this was
• 22:23 - 22:31: around the potential use of academic collaborations and things like that as well that can,
• 22:31 - 22:35: you know, possibly enable you to get more research done on your targets and things.
• 22:35 - 22:41: How does that get viewed and how do you look at utilizing that part of the research community
• 22:41 - 22:45: to help aid in your programs and development from a biomarker standpoint?
• 22:47 - 22:51: I can, you know, speak a little bit from Pioneer’s perspective and Nadine you can chime in.
• 22:51 - 22:59: I think because we were some of the first folks to really do a lot of the work on TREM2,
• 22:59 - 23:06: now TREM1, and then I’m assuming it’ll also be true for Marco as well, you know, we talked
• 23:06 - 23:10: to a lot of academic groups and they’re like, we don’t have an antibody that works in human
• 23:10 - 23:12: tissue for IHC for TREM2.
• 23:12 - 23:13: Like, we don’t have one.
• 23:13 - 23:14: We need this.
• 23:14 - 23:15: We need help.
• 23:15 - 23:18: And we’ve done that work now.
• 23:18 - 23:26: And so we can share that knowledge and kind of grow the pie of knowledge about TREM2 expression
• 23:26 - 23:28: and malignant densities.
• 23:28 - 23:34: And that’s, you know, and then Abcam can supply the antibody, which is great.
• 23:34 - 23:39: So, you know, I think that that’s a way that, you know, we can collaborate with academia
• 23:39 - 23:43: and it benefits us and then at the end of the day it’s benefiting patients, which is
• 23:43 - 23:45: what our goal is, right?
• 23:45 - 23:47: And Radha at Merck, how?
• 23:47 - 23:48: We do.
• 23:48 - 23:51: We do perform a lot of collaborations with academia.
• 23:51 - 23:56: There are investigative-led studies that are driven as well, not only for established
• 23:56 - 24:01: assays, but even for, let’s say, epidemiology, one of the data-driven studies as well.
• 24:01 - 24:07: So it’s a lot of, it’s quite open and there is a lot of interaction that happens across
• 24:07 - 24:10: multiple centers globally as well.
• 24:10 - 24:14: I guess from an Abcam perspective, there’s a similar collaboration network that we’ve
• 24:14 - 24:15: got with academia.
• 24:15 - 24:21: It may well be the same people, you know, and trying to make sure that we often are
• 24:21 - 24:28: fairly early stage or coming off the end of the pipeline, we’ll go into our, in order
• 24:28 - 24:32: to make sure that the quality is in there to confirm that in detail.
• 24:32 - 24:38: So, you know, getting all those to link up and that potentially, whether we’ve got
• 24:38 - 24:42: somebody that may be able to help us and help you to obtain beneficial.
• 24:42 - 24:46: I think the collaboration is extremely critical across industry and academia and
• 24:46 - 24:49: everybody else.
• 24:49 - 24:53: Yeah.
• 24:53 - 24:57: And, you know, we try to publish to the extent that we can, you know, assuming
• 24:57 - 25:01: we’ve covered everything from an intellectual property perspective and a
• 25:01 - 25:07: confidentiality perspective.
• 25:07 - 25:12: But, you know, we’re very focused on getting this knowledge out there.
• 25:12 - 25:13: I mean, it obviously helps, you know, build our reputation and build, you know, our
• 25:13 - 25:19: network with clinical investigators and, you know, academic investigators that we want
• 25:19 - 25:20: to collaborate with.
• 25:20 - 25:24: But it’s also kind of, again, growing the pie of knowledge around these targets
• 25:24 - 25:27: that we think are going to be revolutionary for immuno-oncology treatment.
• 25:29 - 25:34: And I appreciate we’re kind of coming up to the initial half an hour of the conversation.
• 25:34 - 25:43: And so one of the things that I’d be interested to get each of your thoughts on as we close
• 25:43 - 25:49: out and then start to see if there are any questions from anyone here is, in general,
• 25:49 - 25:54: you know, as we look at science, I think one of the things that we see is that the more
• 25:54 - 25:59: that we can work together, you know, more can be done and there can be improved outcomes.
• 25:59 - 26:05: And as we kind of come out of a, you know, very isolated two years of COVID and not being
• 26:05 - 26:11: able to sit in the room with people and things like that, from your perspective,
• 26:11 - 26:16: as you think about partnering and building connections that are, to your point, all of your
• 26:16 - 26:21: points, you know, really trying to drive patient outcomes and improvements, ultimately,
• 26:21 - 26:27: what more do you think that the life science industry can do, you know, thinking
• 26:27 - 26:32: all the way from academic through to the clinic to help, you know, work together and engage more?
• 26:32 - 26:41: What else do you think that we could be doing to help improve that connectivity to make
• 26:41 - 26:46: that journey smoother from all of the people who engage in this sort of field?
• 26:42 - 26:43: Will, take off.
• 26:43 - 26:50: The central bit, I think, is the antibody and then it’s the data that goes alongside
• 26:50 - 26:54: that, whichever, you know, it’s in a tissue type of some of the sections, whether that’s
• 26:54 - 27:01: in an academic setting or it’s in a clinical setting or it’s in, you know, it’s in a biotech
• 27:01 - 27:04: setting, it’s that the antibody is the fixed point, right?
• 27:04 - 27:08: And the production of that antibody and the quality of the antibody, but that’s the kind
• 27:08 - 27:10: of glue that sticks to that.
• 27:10 - 27:15: And as you said earlier, to get it at an earlier stage so you don’t have to change your mind
• 27:16 - 27:19: It just makes the flow a lot easier.
• 27:20 - 27:26: Yeah, it’s all about starting early, working together and having that discussion very early.
• 27:26 - 27:32: That’s probably the key to making sure that we’re able to go across and having transparent
• 27:32 - 27:36: discussions about, you know, all the hiccups that come halfway through or during the course
• 27:36 - 27:40: of that and having that collaborative work.
• 27:40 - 27:43: I think it’s the early start is all that I can think of.
• 27:43 - 27:46: Yeah.
• 27:46 - 27:53: I already mentioned this before, but I think, you know, for early venture-backed startups
• 27:53 - 27:58: that are probably doing a lot of this work for the first time, from Pioneer’s perspective,
• 27:58 - 28:05: we found this collaboration critical and kind of the guidance through the process of this
• 28:05 - 28:09: is, you know, these are some of the steps that you’re going to ultimately end up taking
• 28:09 - 28:10: on the business side.
• 28:10 - 28:13: And we had consultants helping on the technical side as well.
• 28:13 - 28:19: But, you know, that could be codified into, you know, workshops or things like that,
• 28:19 - 28:23: where you could come together with pharma and then teach us.
• 28:23 - 28:28: Being selfish here, but, you know, teach the biotech community.
• 28:28 - 28:34: And frankly, a lot of academics, especially in the San Francisco Bay Area, where we’re located,
• 28:34 - 28:36: are thinking about starting companies.
• 28:36 - 28:39: And they’re thinking about companion diagnostics as well.
• 28:39 - 28:45: And they probably know a lot less than you do or have fewer resources or points of contact
• 28:45 - 28:46: to reach out to.
• 28:46 - 28:52: And so, I think that the willingness to kind of spread the information and maybe even do
• 28:52 - 28:57: it in kind of a more codified way could be really beneficial.
• 28:58 - 28:59: And Nadine?
• 28:59 - 29:00: Yeah.
• 29:00 - 29:02: I mean, I agree with everything that’s been said.
• 29:02 - 29:08: Just maybe one thing to add, more like to connect between where the academia and industry
• 29:08 - 29:14: – I feel that it would be also great to get more in touch with those CAP CLIA labs
• 29:14 - 29:16: or IHC labs that run those assays.
• 29:16 - 29:21: You know, I know there’s the big ones, but also very early on, as Alicia mentioned,
• 29:21 - 29:25: small companies like us will go to first a just CAP CLIA lab, not a full – that doesn’t
• 29:25 - 29:27: maybe develop full CDX yet.
• 29:28 - 29:32: And these are the labs that are key because they’ve been using lots of these reagents
• 29:32 - 29:36: and they can tell us, hey, you know, make sure that you talk to Abcam or what does
• 29:36 - 29:37: Abcam say.
• 29:37 - 29:41: So, when Alicia was thinking about those works, I’m thinking quite it would have
• 29:41 - 29:48: been nice that Abcam, like you talk to those CROs and make sure, you know, all of these
• 29:48 - 29:53: collaborations are there because they are the ones who ask about stability and
• 29:53 - 29:54: expiration date.
• 29:54 - 29:55: It’s top of Nadine’s head.
• 29:55 - 29:56: And record that.
• 29:56 - 29:57: Yeah.
• 29:57 - 29:58: Record that PDF.
• 29:58 - 30:00: And we’re like, okay, Abcam.
• 30:00 - 30:02: We have to talk to them.
• 30:02 - 30:08: So, I think they are also a key in between for early stage reagents.
• 30:08 - 30:09: Yeah.
• 30:09 - 30:11: It’s a great point.
• 30:11 - 30:12: Excellent.
• 30:12 - 30:17: Well, I appreciate everyone’s thoughts on this.
• 30:17 - 30:24: I guess one final question, maybe for Alicia and Radha, and I know you’ve touched on
• 30:24 - 30:28: some of these things early, but, you know, if you’ve got people thinking about people
• 30:28 - 30:32: who are embarking on this journey, you know, what would your piece of advice be as they
• 30:32 - 30:37: start to, you know, think about planning biomarker programs that might lead to the clinic?
• 30:37 - 30:40: Think early, I feel is like definitely a good idea.
• 30:40 - 30:41: Yeah.
• 30:41 - 30:43: That seems to be a theme, right?
• 30:43 - 30:48: I mean, I think, you know, this is just kind of a part of our life at Pioneer, and I’m
• 30:48 - 30:52: sure, you know, everyone’s company here is just, you know, scenario planning and making
• 30:52 - 30:56: sure that we’re planning for different eventualities, right?
• 30:56 - 31:01: So, Nadine talked about, you know, the off-the-shelf catalog antibody that we’re leveraging,
• 31:01 - 31:06: but also looking at that antibody and seeing if there are potential liabilities that we can
• 31:06 - 31:10: engineer out, what should we do with those, and thinking about that at the same time,
• 31:10 - 31:15: parallel processing those, I think is, the goal is that that’s going to pay dividends
• 31:15 - 31:17: later for us.
• 31:17 - 31:22: And Radha, any thoughts from your perspective and experiences?
• 31:23 - 31:26: Not much that I can add, I suppose.
• 31:31 - 31:32: Perfect.
• 31:32 - 31:35: Well, thank you very much for the time.
• 31:35 - 31:39: I think now we can open up if anyone has any questions for the panel.
• 31:42 - 31:43: Bill?
• 31:43 - 31:45: We need you to speak into a microphone.
• 31:45 - 31:49: I will just quickly say that, so it gets picked up on the recording.
• 31:49 - 31:55: I think it’s really encouraging that you’re taking such an advanced approach so early,
• 31:55 - 32:02: because I come from the CDx commercial area, and the biggest issue that we see coming
• 32:02 - 32:09: to us is that people made poor decisions early that did not set them up for success at the
• 32:09 - 32:10: CDx level.
• 32:10 - 32:16: And so, it’s really, you can’t start early enough to make good decisions, not necessarily
• 32:16 - 32:22: expensive decisions, but good decisions that will set you up better when you come to
• 32:22 - 32:29: somebody down the road and say, hey, I need a clinical trial assay in a year, and what
• 32:29 - 32:34: can you do?
• 32:34 - 32:37: And the worst thing you can do is tell them that I have nothing, and it’s going to take
• 32:37 - 32:40: a year and a half or two years, and your drug’s going to be boring.
• 32:40 - 32:43: And so, just keep thinking about commercialization and make the appropriate decisions
• 32:43 - 32:51: where you’re at or the time you’re at that will set you up to be better off later.
• 32:51 - 32:52: Yeah.
• 32:52 - 33:01: No, I think we were fortunate at Pioneer that we have such a great team lead on this work,
• 33:01 - 33:08: and we found really good consulting guidance, and that was exactly the advice we were given,
• 33:08 - 33:12: and we made sure to heed it, right?
• 33:12 - 33:18: Because nobody wants to be the person who didn’t listen to that advice and then be facing
• 33:18 - 33:19: a delay, right?
• 33:19 - 33:27: That destroys value for our shareholders, but delaying what we think is going to be
• 33:27 - 33:40: a really transformational therapeutic for patients, that’s the worst nightmare scenario.
• 33:40 - 33:43: So, what is a specific tumor like?
• 33:43 - 33:48: Soluble tumor, or liquid tumor, or whatever it is?
• 33:48 - 33:51: You can do the biomarker analysis.
• 33:51 - 33:53: For our programs?
• 33:53 - 33:55: Yeah, for the Abcam.
• 33:55 - 33:56: Oh.
• 33:56 - 33:57: That’s a valid question.
• 33:57 - 34:04: So, I mean, we have a specialization in NIC, but we test all our antibodies inside the
• 34:05 - 34:07: chemistry, so if it’s a liquid biopsy, it’s covered.
• 34:07 - 34:10: We do flow cytometry, fixed or fresh.
• 34:10 - 34:18: We look at IP, we go with some blot, we’ve got blot, we’ve got pairs, yeah.
• 34:18 - 34:25: We’re extending out further into things like that, so there’s a number of different options
• 34:25 - 34:31: available to you as you kind of build where you want to take that.
• 34:31 - 34:32: Okay.
• 34:32 - 34:39: This is a question for Pioneer.
• 34:39 - 34:45: What’s your approach for how you’re using the IHC assay with the antibody for TREM2,
• 34:45 - 34:49: TREM1, whatever you feel like speaking to, in terms of primary, secondary, exploratory
• 34:49 - 34:56: endpoints, and sort of your experience for the different levels of required data and
• 34:56 - 34:59: level of validation to be able to do that?
• 35:00 - 35:05: So, I can start off, and then Nadine, you should chime in.
• 35:05 - 35:13: So, right now, for our TREM2 program, we’ve just gotten done with the Phase 1, and now
• 35:13 - 35:20: we’re moving into Phase 1b expansion, and in Phase 1, we were looking at archival specimens
• 35:20 - 35:27: and really doing an exploration of looking at those archival specimens, what kind of
• 35:27 - 35:30: expression levels are we seeing in our Phase 1b.
• 35:30 - 35:35: We’re going to be looking at pre- and post-treatment biopsies, and really, some of the
• 35:35 - 35:41: questions that we’re trying to answer there are, you know, is there a relationship between
• 35:41 - 35:44: our target’s expression and patient outcomes?
• 35:44 - 35:49: And then that’s going to help inform us in our next trial, you know, is it going to be
• 35:49 - 35:53: a fact that we’re going to, you know, be better off if we select?
• 35:53 - 35:58: And so, I think broadly, that’s really our approach.
• 35:58 - 36:05: This, you know, Nadine mentioned previously that we explored filing an IDE early with
• 36:05 - 36:09: the FDA, and the feedback that we were given, which made a ton of sense and we agreed with,
• 36:09 - 36:17: is we don’t know a priori that a certain level of expression of our targets is going to have
• 36:17 - 36:22: a certain outcome, because our targets are on immune cells.
• 36:22 - 36:29: We don’t, it’s not that, you know, if you, that we’re looking at the tumor cell, right?
• 36:29 - 36:34: And then it has a little bit more of a, you know, predictive kind of logical results that,
• 36:34 - 36:39: you know, you’re targeting, you know, 90% of the tumor cells, you’re going to have such
• 36:39 - 36:40: and such reaction.
• 36:40 - 36:42: We’re looking at, you know, immune cells.
• 36:42 - 36:50: And so, we’re really looking to leverage this Phase 1a and Phase 1b data to help us
• 36:50 - 36:52: answer some of those questions in our subsequent trials.
• 36:52 - 36:53: But Nadine, I don’t know.
• 36:53 - 36:55: Maybe I’m going to add just to the point.
• 36:55 - 37:00: So, at this point, as Alicia mentioned, it’s mostly exploratory, but we’re using the IHC
• 37:00 - 37:06: assay both for target expression for, as Alicia mentioned, one day to see if we need to
• 37:06 - 37:08: select per indication with a specific threshold.
• 37:08 - 37:13: But second, for pharmacodynamics to confirm proof of concept mechanism of action.
• 37:13 - 37:19: For example, we know that the PI314 therapeutic antibody depletes TREM2 cells.
• 37:19 - 37:24: So, it’s really by IHC pre and post that we can measure that reduction.
• 37:24 - 37:31: And of course, use that IHC assay with other immune markers in a multiplex or monoplex
• 37:31 - 37:35: because everyone is about spatial interaction, spatial distribution.
• 37:35 - 37:42: And our hypothesis is to convert cold or desert tumor or excluded tumor into hot.
• 37:42 - 37:49: So, that IHC assay is very important to be able to see both the MOA as well as all of
• 37:49 - 37:54: the pharmacodynamic changes and, of course, correlate the tumor microenvironment down
• 37:54 - 37:56: the line if we see clinical response.
• 37:56 - 38:02: And just to add to Alicia about some of the target expression and the feedback from the
• 38:02 - 38:08: FDA or things that we are now learning, we’re the first one to look at TREM2 and TREM1
• 38:08 - 38:10: in the clinic in an IHC assay.
• 38:10 - 38:14: And we work with lots of pathologists, and it’s very challenging.
• 38:14 - 38:20: Similar to the PD-L1, maybe TREM1, TREM2, and other myeloid targets is a whole different
• 38:20 - 38:23: story.
• 38:23 - 38:25: You’re looking at an immune infiltrate.
• 38:25 - 38:28: It’s not present on the tumor.
• 38:28 - 38:30: It depends on how much macrophage infiltration.
• 38:30 - 38:33: The scoring system is very different.
• 38:33 - 38:39: It doesn’t require innate score maybe, right?
• 38:39 - 38:40: So, it’s in the CDX field, we see also challenges beyond just the reagent.
• 38:40 - 38:46: It’s what are we measuring and how can we measure it on one core biopsy on one section.
• 38:46 - 38:52: So, these are the other things that we are thinking about in terms of this as a biomarker
• 38:52 - 38:55: and if it potentially could become a CDX.
• 38:55 - 38:56: Sorry.
• 38:56 - 38:57: So, yeah.
• 38:57 - 39:01: So, then as a follow-up, so how are you approaching being able to define what scoring
• 39:01 - 39:07: system or image analysis approach or anything for your IHC assay that you’re developing?
• 39:07 - 39:09: So, we work with the CAP CLIA lab.
• 39:09 - 39:15: And so, we went through multiple scoring strategy, multiple intraday precision, intrapathologist
• 39:15 - 39:16: precision.
• 39:16 - 39:24: And so, at this point, we like digital pathology, but we know the FDA is not yet ready
• 39:24 - 39:25: to move so fast.
• 39:25 - 39:30: And so, one thing we’re doing is collecting both a manual score that resembles kind of
• 39:30 - 39:34: the PD-L1 scoring strategy because we are really just looking at the myeloid cells.
• 39:34 - 39:39: So, it’s an immune score, but also to look at digital pathology and compare and see which
• 39:39 - 39:41: one is more precise.
• 39:41 - 39:45: So, again, that’s another challenge that if it’s going to become a CDX one day, all of
• 39:45 - 39:51: these need to be lined up and we need to make sure that across the board the scoring is
• 39:51 - 39:53: consistent and reproducible.
• 39:53 - 39:55: But we know it’s an immune infiltrate, right?
• 39:55 - 39:59: So, I think that’s a challenge for everyone in this field.
• 39:59 - 40:03: How can you use an IHC scoring when it’s challenging?
• 40:03 - 40:05: What is a score and what does it mean?
• 40:05 - 40:06: What does it mean?
• 40:06 - 40:08: How much do you need?
• 40:08 - 40:10: If it’s positive, how much positive?
• 40:10 - 40:11: You need to be high.
• 40:11 - 40:12: So, this is…
• 40:12 - 40:16: And, of course, we’re learning that different indications obviously look very different
• 40:16 - 40:19: and have a different immune environment.
• 40:19 - 40:20: So, yeah.
• 40:20 - 40:21: Stay tuned.
• 40:21 - 40:22: I guess that’s another…
• 40:22 - 40:25: It’ll be a future poster or presentation.
• 40:25 - 40:28: Yeah.
• 40:29 - 40:34: Thanks for sharing your story.
• 40:34 - 40:40: So, you sort of touched upon the challenges with tissue samples.
• 40:40 - 40:43: I think you sort of alluded to that earlier.
• 40:43 - 40:51: So, a question I have is a major challenge with IHC assay that is tissue availability.
• 40:51 - 40:52: A lot of the tissue…
• 40:52 - 40:58: You know, not every patient will be willing to provide a tumor tissue, and very often
• 40:58 - 41:01: the tissue quality is not great.
• 41:01 - 41:04: So, and I think you also mentioned that you’re using…
• 41:04 - 41:10: Doing, like, longitudinal pre- and post-tissue biopsy to look at target engagement.
• 41:10 - 41:15: So, I wonder, like, what’s your approach, like, in terms of solving, like, issues and,
• 41:15 - 41:18: you know, challenges with tissue availability?
• 41:19 - 41:21: So, to enroll on our…
• 41:21 - 41:25: At least in the beginning of our Phase 1b expansion, it’s going to be a requirement
• 41:25 - 41:26: of enrolling in the trial…
• 41:26 - 41:27: Yeah.
• 41:27 - 41:31: …to be willing to get that biopsy.
• 41:31 - 41:32: Yeah.
• 41:32 - 41:37: So, that would be the baseline, right, or both pre- and post-?
• 41:37 - 41:38: Pre- and post-.
• 41:38 - 41:40: So, we require an archival and the pre- and post-.
• 41:40 - 41:49: The idea from getting the archival is to see if our target is dynamic and is still
• 41:49 - 41:57: expressed, meaning that, do we need a present, fresh biopsy to get the best scoring
• 41:57 - 42:01: strategy?
• 42:01 - 42:07: Because, like you mentioned, it’s very hard for the patient to go through that surgery.
• 42:07 - 42:13: So, for our first initial patient, like Alicia mentioned, we are requiring a pre- and
• 42:13 - 42:14: post- for the target engagement and an archival to see, at least, the first question,
• 42:14 - 42:19: is the target expressed similarly between archival that not collected a long, long time
• 42:19 - 42:23: ago, but at least an archival versus the pre- and then pre- and post-.
• 42:23 - 42:28: But to your point, I see that, in terms of tissue, some core biopsy will fail.
• 42:28 - 42:30: We know there’s a high rate of failure.
• 42:30 - 42:34: And so, it is what it is.
• 42:34 - 42:39: And then, for the pair that doesn’t have, let’s say, a pre- or post-, we cannot make
• 42:39 - 42:41: a comparison, right?
• 42:43 - 42:44: Great.
• 42:44 - 42:49: And by mandating that, how does that affect the patient enrollment into the trial?
• 42:49 - 42:50: Yeah.
• 42:50 - 42:53: I think that’s always the common concern.
• 42:53 - 42:57: And, you know, if you’re out raising money, that’s the thing that venture investors will
• 42:57 - 43:01: push back on is, oh, that’s going to slow your enrollment by, you know, X number of
• 43:01 - 43:03: days or months or, you know.
• 43:03 - 43:08: I think that, you know, that’s, I think, where you really have to rely on your clinical
• 43:08 - 43:15: team to generate the excitement with the investigators to communicate the, you know,
• 43:15 - 43:25: the potential value of your program and, you know, get, you know, the patients to consent
• 43:25 - 43:26: to the biopsy.
• 43:26 - 43:29: But, yes, you are going to have some patients that aren’t going to do it, and that’s
• 43:29 - 43:30: their choice.
• 43:30 - 43:37: But we have not, we have not experienced a significant slowdown that we’re aware of yet.
• 43:37 - 43:44: But, again, we’re at the beginning of our Phase 1b expansion, and we’re getting
• 43:44 - 43:46: patients consented actually pretty quickly.
• 43:46 - 43:47: Yeah.
• 43:47 - 43:51: And also, you know, these are mostly relapsed, refractory patients that probably
• 43:51 - 43:52: exhausted all others.
• 43:52 - 43:53: So, yeah.
• 43:53 - 43:54: Yeah.
• 43:55 - 43:59: So, one question to Abcam as well as to Pioneer.
• 43:59 - 44:06: When you do the antibody selection, as you just mentioned that pre and post PDX is going
• 44:06 - 44:11: to be different expression of certain molecules of certain biomarkers that you’re looking
• 44:11 - 44:12: for.
• 44:12 - 44:18: Also, internalization, expression of epitope, whether it’s available or not, based on the
• 44:18 - 44:20: various other factors.
• 44:20 - 44:27: So, my question is, when you do the antibody selection, how many tumors you check?
• 44:27 - 44:33: You check pre-PDX or pre-chemo or post-chemo or post-PDX?
• 44:33 - 44:40: And does it vary between different tumor types and pre and post and epitopes?
• 44:40 - 44:42: And how do you do the final antibody selection?
• 44:42 - 44:47: Because we all know that if the antibody is not going to detect, then everything is going
• 44:47 - 44:50: to go down the drain or all the following things.
• 44:50 - 44:58: So, and then follow-up question is, if someone wants to work with Abcam, do you have the
• 44:58 - 45:06: different biopsy samples where you can test using your antibody under different tumor
• 45:06 - 45:10: types or IHC or something like that?
• 45:10 - 45:14: I’ll go to the first question, first part of the question.
• 45:14 - 45:19: So, in an early stage, when we’re developing our markers, we’ll do like everybody does
• 45:19 - 45:24:  do a deep dive into the literature set to understand what we're looking for, where's
• 45:24 - 45:26:  the expression likely to be.
• 45:26 - 45:38:  And then our standard TMA set will be 17 different tumor types and cancer, 17 different normals.
• 45:38 - 45:42:  And then if we know that there's a particular disease indication that we want to go for,
• 45:42 - 45:48:  then we'll expand that into, at this stage, it'd be likely to be about 20 breast cancers,
• 45:48 - 45:50:  20 colon cancers.
• 45:50 - 45:56:  But at that point, we're not going into pre and post biopsies, not knowing the clinical
• 45:56 - 45:58:  data associated with that.
• 45:58 - 46:04:  It's difficult for us to pull that together without having a partner who's got a CDX and
• 46:04 - 46:06:  a particular application.
• 46:06 - 46:10:  So that's where we would then potentially work with that partner and understand that
• 46:10 - 46:14:  and assist in that area.
• 46:14 - 46:18:  Now, as I said earlier, we can expand further.
• 46:18 - 46:24:  So if we have only 20 and we feel that it's worthwhile doing them, we can do that to 160
• 46:24 - 46:26:  different TMAs.
• 46:26 - 46:30:  And we're in the same sort of place as anybody else here, which is we can pull that data
• 46:30 - 46:36:  in from providers in a TMA set of pre and post treatment, et cetera.
• 46:37 - 46:40:  But we've got to understand and know what we're trying to achieve, what the treatments
• 46:40 - 46:42:  are.
• 46:42 - 46:46:  And de novo, we probably don't without having a partner alongside.
• 46:46 - 46:52:  The reason I'm asking that question is, for example, a company like Campus, who have
• 46:52 - 46:58:  literally hundreds of post-PDX samples available.
• 46:58 - 47:04:  Do you work with such companies to get access and then validate that particular antibody
• 47:04 - 47:12:  or particular expression of protein and come up with any particular new antibody,
• 47:12 - 47:14:  which you feel at this stage?
• 47:14 - 47:24:  Not at this point, no.
• 47:24 - 47:30:  The rigorous testing we do for our normal catalog antibodies are for the research community.
• 47:30 - 47:36:  But if you partner with us early and you actually have something that has some commercial
• 47:36 - 47:40:  use, we will do more, obviously, if you partner with us.
• 47:40 - 47:44:  Or even if a catalog antibody, we can do more testing.
• 47:44 - 47:48:  And then it is required that you're looking at something like post-resistance, where we
• 47:48 - 47:54:  would need…we normally would not have access to tissue from patients who have had,
• 47:54 - 47:58:  you know, cisplatin or have had, you know, elaporate or whatever.
• 47:58 - 48:04:  But if that's…if you're looking at that pathway, we can help you with that, but you
• 48:04 - 48:08:  have to engage with us earlier to do that on commercial terms.
• 48:08 - 48:14:  But also, this goes on to what we were talking about in terms of working with academics.
• 48:14 - 48:18:  You know, if in a three-way, we're working with academics, they might have access.
• 48:18 - 48:22:  By academics, I mean clinical academics might have access to those tissues, and they might
• 48:22 - 48:26:  be then part of your drug development pathway as well.
• 48:26 - 48:32:  Yeah, I think that's a key point from our perspective is because of the engagement that
• 48:32 - 48:38:  we have with the academic community and looking at, you know, where people are working in
• 48:38
• - 48:44:  that space and can we get them or are they working with our portfolio and testing with
• 48:44 - 48:46:  different tissue types and things like that.
• 48:46 - 48:50:  I think that's quite, you know, that can be very powerful and probably sometimes maybe
• 48:50 - 48:55:  even underestimated in how much people can actually tap into from that academic space.
• 48:55 - 49:01:  And so, that's one of the things, again, as we think about really trying to support
• 49:01 - 49:07:  that flow from discovery to clinic, it is so important in our, you know, in our view
• 49:07 - 49:13:  that as a company engaged really heavily in that research space, before people are even
• 49:13 - 49:17:  thinking about what might happen with that antibody kind of, you know, going into a clinical
• 49:17 - 49:22:  aspect, that we can help be a part of that thinking forward for people as well.
• 49:22 - 49:27:  So, building those kind of relationships academically for us and looking at, you know,
• 49:27 - 49:33:  where is the research going, what sort of diseases are people starting to look at maybe
• 49:33 - 49:39:  developing therapeutics for, how can we help and engage with the community in a very,
• 49:39 - 49:45:  at those very early stages so that when it does start moving and having a clinical life,
• 49:45 - 49:50:  we're also helping aid build that body of information that can, you know, help people move
• 49:50 - 49:55:  forward with their research at a much greater pace and start looking at those kind of things.
• 49:55 - 50:01:  So, from our perspective, I think just as you look at that kind of general community
• 50:01 - 50:05:  aspect of things, that's one of the things that we're always thinking about is how do
• 50:05 - 50:13:  you give the reagent that sometimes might almost, you know, seem not as key at that
• 50:13 - 50:18:  point, but how can we help identify those kind of key points and try and create that
• 50:18 - 50:24:  frictionless experience so that as it moves up to the, you know, value chain with pharma
• 50:24 - 50:28:  partners and developing with diagnostic partners that we've thought that through and we
• 50:28 - 50:32:  can give people that lifecycle as well, but more importantly, you know, really make sure that
• 50:32 - 50:35:  we're a part of the community helping build those data sets and that kind of information
• 50:35 - 50:40:  that everyone can find valuable, both from an academic standpoint, but also as things
• 50:40 - 50:44:  move into industry as well.
• 50:44 - 50:48:  To validate any antibody, you also need to know the intended use and the clinical application.
• 50:48 - 50:53:  So, without having that information, trying to do that up front is going to be a bit of
• 50:53 - 50:54:  a challenge as well.
• 50:54 - 50:56:  So, once we have that, that is going to be helpful.
• 50:56 - 50:57:  Absolutely.
• 50:57 - 50:59:  So, it usually would not be upfront.
• 50:59 - 51:02:  We may not be able to have all of that.
• 51:02 - 51:06:  But when you start working with people like us, then you know that this is your direction
• 51:06 - 51:07:  and this is what's at stake.
• 51:07 - 51:08:  Exactly.
• 51:08 - 51:11:  Then you can start trying to answer the questions as well in parallel.
• 51:11 - 51:12:  Absolutely.
• 51:13 - 51:16:  Are there any other questions?
• 51:16 - 51:17:  Perfect.
• 51:17 - 51:19:  Well, with that, I will thank the panel.
• 51:19 - 51:21:  Thank you everyone for your participation.
• 51:21 - 51:23:  Thank you very much for the questions.
• 51:23 - 51:26:  We will be having drinks.
• 51:26 - 51:31:  Forgive me, out that way, I'm getting a strong point out the door.
• 51:31 - 51:37:  Please, please join us for some drinks and I think some canapés as well.
• 51:37 - 51:39:  But again, thank you everyone for your time.
• 51:39 - 51:43:  I really appreciate the time that you've given us today.
• 51:43 - 51:44:  Thank you so much.
• 51:44 - 51:46:  Thank you.
• 51:46 - 51:47:  Bye everyone.