NorthWest Biotherapeutics Inc (NWBO)

[ae kusterer]

ASM salients:

https://nwbio.com/audio-of-nwbio-2023-annual-shareholders-meeting/


1)MHRA has been wonderful.

They have given us rapid turnarounds more than we could have expected or hoped for in the steps that we've had with them so far.

That doesn't necessarily predict anything, but it's been a really great experience so far.


2)And our Chief Technical Officer, Dr. Bosch, presented all that information in a company presentation during ASCO last year, and it was tremendously important because it showed with the underlying biology that DCVACS is what we've always hypothesized, is that it gave support for the hypothesis that it's a broad spectrum treatment.

We reported that in the examples that were studied in those Mechanism of Action studies, the dendritic cells were picking up from the tumor's tissue sample, the lysate, and presenting to the T cells over 600 different tumor targets.

So when we say it's a broad spectrum treatment, that gives you a flavor of it, and those Mechanism of Action studies were really important to add more scientific underpinning that supports the clinical trial results that we've seen in the patients and help support our MAA.

And it was very important, we use proteomics technologies that are relatively recently developed.

Proteomics, a study of the proteins, active agents, are not as far along as genomic tools, and so we were using quite recent technologies in doing these studies, and that was really important.

3)On another front, we do continue to follow our patients from the Phase III trial.


We do still have patients alive.

I'll remind you that the last patient was enrolled in November of 2015.

4) We also have continuing our ongoing compassionate use program.

We have not had as much activity in that while we've been so occupied with the MAA, but that program continues to give us really valuable real world experience.

In a clinical trial, you try to do everything as cookie cutter as possible, as homogeneous, the same as possible, but that is not the way the real world is.

And so the compassionate use program has been so valuable for us because we've gained a tremendous amount, and we still are gaining tremendous amount of real world experience, basically practicing for when we're able to be commercial.

So we have patients who their tumor tissue sample isn't in the condition that it's supposed to be, or it hasn't been frozen quite the right way, or it was frozen several years ago, or the patients are way outside the age range.

We have patients in their 80s and upper 80s.

So lots of real world circumstances that's really been valuable for us, and I think it's been very valuable for the patients too, which is quite important.

And we are learning lessons.

We have some very nice long-term survivors, eight, nine, 10 years, and so we are learning lessons from the cases of long-term survivors as well.



5)What we are transitioning to now, and we're able to do this because of the FlaskWorks system, is we're transitioning to grade C labs, which would roughly be more like class 100,000 in the US.

In other words, it's a lower level of rigor and sterility.

You can only do that when your whole manufacturing process is done in a closed way.

The word closed is a magic word in the world of medical manufacturing.

When your process is closed, that means it's all kept within a machine or within a bag or within a flask or something that's not open to the air.


6)We anticipate, ultimately, when the building is fully built out, if it's fully built out with C labs, with our current understanding, and the engineers don't change things, we anticipate being able to, up to potentially 15,000 patients a year with all grade C labs in the rest of the building.

So you can start to see, even if we get part of the way towards 15,000 a year, that is an enormous amount of patients, especially for personalized cell therapies.

My understanding is, for example, the big companies who bought the CAR T cell technologies in their first years of commercial operations made 50 patients' products.


7)The FlaskWorks system has enabled us to transition first to being a closed system for the manufacturing steps, and also to start the process of automation, which is a separate thing and an additional benefit.

As we look towards the further development of the Sauston facility, we are moving into all grade C labs from here on out.

8) We anticipate, ultimately, when the building is fully built out, if it's fully built out with C labs, with our current understanding, and the engineers don't change things, we anticipate being able to, up to potentially 15,000 patients a year with all grade C labs in the rest of the building.

9)And the way that Advent is finishing up, even right now, things like the restart of DCVAX Direct, which will be coming up and has done, I'll put a lot of work on that in the last seven, eight months, and let me take on and state how we compensate them under these contracts and that is, that the payment structure provides a pass-through of all baseline costs.

And a fee, if you will, for the administration of it all, which is a 15% on top of that cost.

But Advent doesn't really realize any gain on any of that until they meet the milestones like getting the MAA in or getting the facility going for the next phase of the C services.


10)Now, just recently, we announced one that was particularly big, I mean, ginormous.

And that's the arrangement, the in-licensing package that we did from Roswell Park.

But if you noticed, even in that announcement, we explained that that package from Roswell covered seven years of work by this leading research group on dendritic cell technologies.

But we had also completed last year an in-license of a package of the original, older foundational work that that group had spent 17 years developing at another institution.

And we have in-licensed both of those packages.


11)Now, just recently, we announced one that was particularly big, I mean, ginormous.


And that's the arrangement, the in-licensing package that we did from Roswell Park.

But if you noticed, even in that announcement, we explained that that package from Roswell covered seven years of work by this leading research group on dendritic cell technologies.

But we had also completed last year an in-license of a package of the original, older foundational work that that group had spent 17 years developing at another institution.

And we have in-licensed both of those packages.

And we purposefully stayed in stealth mode while we put all the pieces together.

Because we believe in our own analysis that the sum is greater than the parts.

And those two packages together have some just wonderful things in them.

They include enhanced versions of dendritic cells.

They also include technologies that are complementary to, to use with dendritic cells, for example, in a combination treatment regimen in a trial.

Or agents to just be immune booster agents, that kind of thing.

And if you think about it, interestingly, this collection of new tools or technologies gives us a lot of growth opportunities, which we can use together with our existing DCVAX platforms, which, as you know, we have two versions of the platform, DCVAX L for operable tumors, DCVAX Direct, that you haven't heard much about recently, but which will be coming up again now, I'm happy to say, for inoperable tumors.

We can use these complementary technologies with our own DCVAX platforms.

We can even use them with other kinds of agents.

You can use a conditioning regimen, for example, that's meant to condition the patient to have more of a response to immune therapies, or is meant to, as people like to say, reprogram the tumor microenvironment to be more conducive to an immune response.

You can use those with any type of agent.

So we could do partnering with other companies who have biologics or targeted therapies or checkpoint inhibitors that could either be with the dendritic cells included or with just the other agents.

So we start to have a pipeline that has complementary things, but has many permutations and combinations that we can do.

And obviously, one of the really nice things about the package, and we were surprised because people maybe didn't quite register, but as we said in our announcement, there are two phase two trials currently underway with these technologies that we inlicensed.

And these two clinical trials are fully funded by grants and they're being fully carried out by the investigators.

So we don't pay anything and we don't do anything.

But these are the results of technologies that we now have.

So those will be going along in the background in parallel while we're busily working on the MAA and all of that.

And if they produce positive encouraging results, we will then take them on into the phase three.

And we think Roswell, which is an absolute top tier, if you don't know, it's a very prestigious institution, very top tier cancer center, we think they've done a marvelous job of developing the technologies at the research stage and at the early clinical trial stage and even now into the mid stage clinical trials.

And we're really gratified that they chose us to pass the baton to take it forward for late stage clinical trial and hopefully eventually the commercialization.

So these are some of the intellectual property, but we've been quietly in licensing quite a number of different pieces of technology that we feel will be useful building blocks in building our franchise.

12) And we've also been putting some collaborations in place.

We haven't announced those yet, but those will be something that will be coming along.

13) Intellectual property.

Let me start with the big picture point.

Our goal is to build a franchise in dendritic cell technologies.

We want to build a leading and preferably the leading franchise in this area.

The mainstream thundering herd hasn't yet fully recognized the special capabilities of dendritic cells, but it's starting to happen more and more.

If you noticed, for example, when the federal government created a new agency modeled on DARPA, the Defense Advanced Research Projects Agency, which they call ARPA-H for health and wellness research project, the very first grant that this elite technologies of the future agency awarded was a large $25 million grant for dendritic cell technologies in academic setting.

And that's just one glimpse, but increasingly people are beginning to recognize the special capabilities of dendritic cells.

So we are working busily to build a dominant franchise in the meantime, before the thundering herd arrives or while they're on their way.


14)DC Vax direct very near and
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dear to our hearts we have been eager to restart this program for a long time and
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we the first thing of course that we need to do is restart the manufacturing as it
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turns out and this will be something that will will make a public announcement
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when the time is right in any time that you do a technology transfer process
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because that product was only ever produced in the US by parties who are no
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longer there and so we had to do a technology transfer process to the
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sauce and facility whenever you do a technology transfer process you have to
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draft a whole new set of SOP standard operating procedures regulatory
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documents all of that and usually a technology transfer especially for a
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cell therapy is a minimum of at least six months of work and then we've had
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two additional challenges which I think we're we're on our way to having behind
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us one that related to the machine that we use for the first stage of the
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process and one which related to some key ingredients in the process and when
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we come to that announcement we'll sort of explain all that but suffice it to
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say restarting the manufacturing process is a significant priority for us in this
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going forward period and you'll be hearing from us about that and then once
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we've got the manufacturing restarted okay then we come to the last grouping


15)MHRA has been wonderful.
0:12:55?–?0:12:57

They have given us rapid turnarounds more than we could have expected or hoped for in
0:12:57?–?0:13:05

the steps that we've had with them so far.
0:13:05?–?0:13:08

That doesn't necessarily predict anything, but it's been a really great experience so
0:13:08?–?0:13:14

far.


16) And NICE HAS BEEN wonderful.


17)
this we want to focus particularly on clinical trials where tumor response
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meaning tumor shrinkage can be the endpoint as opposed to overall survival
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being the endpoint why because if you're going to see tumor shrinkage from a
1:20:02?–?1:20:07

treatment you can typically potentially see it in a matter of months and
1:20:07?–?1:20:12

survival takes years and years and we've just got done conducting one of the
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biggest one of the longest well you know a real a major landmark in the field in
1:20:18?–?1:20:27


18)
we're quite open to partnering I just I gave you a couple examples earlier of
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potential partnering especially now that we have this this tool chest of all these
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more technologies but we're open to partnering we'd like to be where we see
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a partnering that could have either strategic value or financial value for
1:21:27?–?1:21:34

both and as we think about it a partnering could be a regional partnering
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geographic region we have made a point of filing our IP and maintaining our IP in
1:21:40?–?1:21:47

countries wide range of countries and we try to build for the day when it would
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be useful for type of partnering or it could be partnering for particular
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application so we we will be open to that and see what makes sense last but
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19)
not least of some folks have asked about up listing certainly everyone would love
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to be on a national exchange rather than the OTC and we do realize we do know
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that you guys are having difficulties some of you with the brokers and they're
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making it difficult sometimes with our shares while we're on the OTC so we we
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will be looking for when the strategic timing is right we're not quite there
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yet but we will be looking for that so as we look at the going forward period
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so let me close with just a couple of concluding comments first of all I've
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20)
just reminding you again but we have said in every presentation we are eager
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to combine DC Vax L with these other combinations and so one of our many
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priorities for the going forward period is to do one or more of those
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combinations and we've received considerable interest from various
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parties for that so we are looking forward to that one thing I will say
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