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Talking Biotech is a weekly podcast that uncovers the stories, ideas and research of people at the frontier of biology and engineering.
Each episode explores how science and technology will transform agriculture, protect the environment, and feed 10 billion people by 2050.
Interviews are led by Dr. Kevin Folta, a professor of molecular biology and genomics.
Hi everybody, and welcome to this week's Talking Biotech podcast. Now we're in the 11th year now, and one of the unpleasant realities of time is that the people you care about might experience declines in health. And I've had friends, I've had colleagues, spouses of colleagues and friends that have experienced hardship in their lives with degenerative disease and long-term developmental disease, things like cancers, different cancers, really start to plague your cohort.
And one of the things you notice is that although we've come a long way in terms of treatment, that some of the treatments, especially for advanced care, tend to be extremely harsh and that the treatments can be as hard as the problem itself to the point where people who you really care about and love are saying, I want to defer treatment and just let it go because the treatment is so harsh. And
You know, we're wrestling with this with a few folks right now. I know and my heart goes out to them during these trying times But what if there were drugs that could be tuned and drugs that could be targeted and we're seeing this more and more with the immunotherapy approaches But what if there were some drugs that were specifically targeting us? Tumors or other tissues that could then deliver a therapeutic environment
directly to those tissues and alleviate the problems that happen in other types of cells or other types of tissues. And this is one of the issues that we're seeing with conditionally active therapeutics. How do we come up with drugs that can be processed or targeted in a way that makes them specific for a given problem? And this is really exciting. So I'm speaking today to two representative of Bonham therapeutics. This is Dr. Neela Patel. She's this
Kevin Folta (03:18.157)
chief business officer and Dr. Diane Hollenbaugh. She is the chief scientific officer at Bonham. So welcome to the podcast.
Diane (03:29.026)
Thank you.
Neela Patel (03:29.167)
to be here with you, Kevin.
Kevin Folta (03:31.311)
Yeah, I'm really excited because this is such a cool topic and you know, we're going to discuss the conditionally active biologics. This is an emerging class of drugs. It's apparently safer, more effective than conventional therapies and specific in its application. But let's start with the current situation and I maybe framed it a little bit, but you're much more of the experts than I am. What are the problems that conditionally active biologics are trying to solve?
Diane (04:03.256)
So the real problem is that when you have a drug, you take a pill or you get an injection, that drug goes everywhere, everywhere within the body. And there's no way that it knows where to go. You sprain your ankle, you take an ibuprofen. It doesn't know to go to your ankle versus your wrist or wherever else. And so you get that activity everywhere. And so if it is an activity that can cause other problems, like a toxicity, like with chemo, it goes everywhere, not just to the cancer.
then you have that problem of that toxicity and it's both horrible for the patient, but it's also that you can't necessarily get as much drug there as you need. And so the problem is how to get the drug to where you need it to be, only active where you need it to be and not be active anywhere else.
Kevin Folta (04:52.729)
Yeah, that's a really interesting angle because I love your example of ibuprofen for a sprained ankle. I mean, it's perfect example. But what are some examples of current therapies with significant side effects from toxicity that conditionally active biologicals show potential in addressing?
Diane (05:12.398)
So there's a number of different ways people are trying to do things that are conditional or targeted. So just to start with a little bit, people talk about the ADCs, antibody drug conjugates. And really what it is is finding different ways to specifically bring the drug right where you need it to be. For the conditionally active biologicals, what we're doing is we're using biological drugs, not small molecule drugs, but proteins. And here what they are is these are proteins that we're taking from nature. They're things that...
your body already uses in different ways, and we're trying to use them as drugs. Now we're taking them out of their normal context. So they go everywhere, they do all kinds of things. So one specific example is IL-2. So IL-2 is an approved drug. It's amazing. What it does is it targets the immune system and it can drive an immune response against your cancer. And so for the subset of patients for whom it works, they basically, we cautiously use the word cure.
They get these long-term responses in a very small subset, an indication. The problem is, not only does it lead to that, the flip side is that the patients often end up in the ICU or worse, there's patient deaths because of the drug itself. So that's a pretty big, pretty big flip side to that efficacy. And the problem is, is that protein, it does all these other things that are toxicities that aren't related to the good thing that it does. And so...
trying to find a way to take that biological protein and target it right to the cells that need it that lead to efficacy without having it doing all this other business that's the toxicities.
Kevin Folta (06:51.247)
Yeah, I think I've seen this described as on target off tumor toxicity, right? you're, you're, you're hitting the target, but there's other problems associated. Is that what I'm looking at?
Diane (07:04.918)
It is. It is. And there's also one more specificity to that when people use that phrase. So like IL-2, the way to say that is that there's IL-2 receptors in lots of places. And so the IL-2 goes to all those places that don't have anything to do with the tumor. And so that's what it is. It's on target. It's an on target activity. It's what that protein is meant to do. But it's not on the tumor. And it's not related to that tumor biology that we need to be affecting.
Kevin Folta (07:33.859)
Yeah, and I guess this is as we enter the world of immunotherapies and some of the ways that these, you know, just have been astounding. We've been talking about them for a few years here and there's a lot of interesting things we're learning about them as we go along. And why has it been so difficult to reduce the toxicity of amino cytokines and make them more effective?
Neela Patel (07:47.495)
Thanks.
Diane (07:54.318)
So the immunocytokines part of the issue is that they are so powerful. That's the other side of that pancake. They're so powerful. And so being able to have them be targeted and not active anywhere else is difficult because you inject them, it doesn't take very much to get all this other activity. So it doesn't take much at all. And so even if it's targeted and it's hooked to an antibody that takes it to the right cells it needs, it's still active and it still brings all that toxicity with it.
really being able to get around that systemic activity is where we have to go, and that's where the conditionally active ones come in.
Kevin Folta (08:32.291)
Yeah, that's kind of where we're going. So you're getting around the systemic issue. If you have a conditionally active bio...
How are they different from what we have already? guess that's really the big question. know, just for the listeners to bring everybody up to speed. How are they different from what we're doing now?
Diane (08:45.934)
Yeah.
Diane (08:52.238)
So what these are are ways to have the molecule be off, have that protein not be able to be active anywhere else. And so there's several different ways people have been doing this to try to make things be conditional. so conditional meaning it's only on in the place where you need it to be, but also it's off everywhere else. That's a very important other side of that. And so people have been trying to do this in a number of different ways, different kinds of masking techniques. I think one of the ones that people are probably most familiar with might be the
proteases. So in cancer, tumors make, it's just the nature of tumors is they have this proteases around them. And so people take these masks, make them so that they block that activity until they get to the tumor, then the proteases cleave off that mask and now you have activity there. So things like that, that people have been trying to do to get rid of that systemic activity. So it's only active where you want it to be.
Kevin Folta (09:46.925)
Yeah. And I think so just for the listeners that proteases are these proteins that do protein processing according to sometimes a very specific cleavage. And we see it like an insulin is a great example that you have pre pro insulin that to proteolytic cleavage cleavages give us the active form of the hormone. The same thing is applying here in the delivery of the drug that a locally produced protease might be able to do that and unmask it.
The other way of approaching this might be through something like monoclonal antibodies. And these are useful tools introduced in treating specific disorders already. We saw in COVID other places, but can you tell me a little bit about what monoclonal antibodies are and why are they useful tools in treating specific orders disorders?
Diane (10:40.184)
So monoclonal antibodies are part of our normal immune system. It's what our body does to fight infections. It makes these proteins that are beautifully specific. And we always draw them as a Y because they are a symmetric molecule. And so we draw them always as a Y because they have two binding sites that are identical. And what happens is when your body, you your immune system sees an invader, you get the flu, you have a virus, you have antibodies that bind to that.
And as soon as your B cells know that they're making one that's a good one, they make a whole lot more. And the key is that what we're using them for to take what we've done to exploit them is that they are fabulously specific. And so we can create them in the lab to make these very specific antibodies. Now, biologically, what antibodies do is they block things. So your body will make antibodies against the flu virus, and it'll make antibodies that block that flu virus from infecting your cells.
which is beautiful, right? So we can do the same thing. We can make these antibodies to block what we want it to block, whatever we want it to do, what we want it to bind to. And over the last several decades, we've learned how to create them, how to manipulate them, how to produce them at scale so they can be a drug, because that's also a really important part of it. You got to able to make it. And so they have this fabulous specificity for...
whatever it is we design them or make them or create them to bind to so we can use them as drugs.
Kevin Folta (12:07.213)
Yeah. So this is really cool. So we talked about this idea of, you know, cleave proteolytic cleavage in order to activate something others with, know, directed targeting, you know, but what is the mechanism behind how a conditionally active biological is turned on and off? Because this is a big deal. mean, you're making a monoclonal antibody. So is it, is it really a, you said before an unmasking of function.
Or is it really targeting the drug to the right place?
Neela Patel (12:38.471)
Both.
Diane (12:38.944)
It's a bit of both. Yes, it's a bit of both. So we use the antibodies. So really what we need is we two things. We need to be able to get the drug to stay in the right place, and then we need a way to turn it on and off. So the first step, get it to the right place. That's a regular antibody. That's how antibodies work. And a regular immunocytokine can bring that cytokine to the right place. It's not off, but that antibody can bring it to the right place. The mechanisms we can use for turning it on and off.
There's a couple of different ones. So one is the proteases that I mentioned. So now you have the cytokine in it goes to its place. It hangs around now in the tumor because it's stuck there by this antibody. It has time to cleave and then it releases the cytokine. For what we do at Bonum is a little bit different. We use antibodies slightly differently. We have a mechanism where we use the antibodies as the off switch as well as the turning on switch. So it's slightly it's a little bit different use of the antibodies. So
In our system, in our technology, we're using the antibodies both to deliver it to where it needs to go, as well as to be the on and off switch for the biologic that we're delivering.
Kevin Folta (13:48.208)
Okay. So this is kind of cool. Cause we, we, talked about antibodies again, you know, I mentioned COVID for instance, and how this might be able to turn off the virus by binding the specific sites on targeted cells, for instance. So there's ways of like that kind of, um, uh, interfering with, you know, binding that kind of thing. But when we're talking about your example, let me backpedal a little bit. So we talked about amino cytokines. You brought this up too is
Tell me what that is exactly and why they're important in cancer therapies.
Diane (14:21.486)
Immunocytokines are a class of drugs that we're still working on how to get them to be good useful drugs. They're emerging. But what an immunocytokine is, is it's an antibody that has a cytokine attached to it. So that antibody is what brings it to a target. It brings that along, that cytokine to that location. So a regular immunocytokine is just that. It's a cytokine that's attached to a targeting antibody to bring it somewhere in particular.
Kevin Folta (14:50.381)
I see. So what exactly is a cytokine for those of us who aren't doing, you know, cancer biology?
Diane (14:53.67)
Apologies, I slipped in between those words a lot of times. Thank you for calling me out on that. So cytokines are a particular class of proteins. We can make conditionally active biologics, biologics being the broad one. A subset of biologicals are proteins that are these cytokines. And cytokines are proteins that are active in the immune system. And they're part of the system where
Neela Patel (14:53.924)
What?
Diane (15:20.926)
Different immune cells talk to each other. So a given cell might get activated in a certain way and it wants to, you need to induce a response in another set of cells. It may produce these cytokines and it secretes these proteins that now signals on these other cells to amplify a response or direct a response or turn off a response, depending on what it is.
Kevin Folta (15:41.521)
that's an excellent example. So excellent description. So are there ways in which cancer cells or other types of neoplasias actually evade cytokine signals?
Neela Patel (15:53.435)
Mm.
Diane (15:53.496)
They do. They get selected for. So part of what happens when you have cancer is that we get cancer cells in our bodies all the time and our immune system clears it out. It's part of that process of something turning into cancer that those transformed cells that are the cancer cells have a way to get around this immune response, whether that's hiding from it and cloaking or finding ways to silence the immune system around them.
So yes, the cancer cells themselves, the other thing that cancer cells do though, in addition to potentially producing the things that suppress the immune system, they also recruit other cells. They form this network. They bring in these other cells that also do that sort of thing. So a solid tumor is more than just a ball of transformed cells. It's this network of all these other cells that the transformed cells bring in as well. And so the cytokines and the biologics that we're talking about,
act connect both either directly on the transformed cells or on the immune cells or the stromal cells, the other cells in that environment that that cancer cell needs. And if we can mess that up for that cancer cell, then it'll die. And now we have it there.
Kevin Folta (17:09.763)
Yeah, and that's especially important because cancer cells are in solid tumors are constantly evolving. And so these things are changing all the time. So having some sort of therapeutic, which has a little more of a general aptitude to be able to address a large number of cell types as they're changing still would be a really potent thing. So what is the biggest challenge in this new class of drugs? So for instance, you know, challenges come with different types of therapies.
because of their molecular complexity and how do these affect analytical development?
Diane (17:45.934)
So some of the ways that we do this, it does affect the analytical development and we always have to make sure that we're doing something, you know, it's one thing to make interesting proteins, it's something more to make a good drug. And so it has to be something that can be produced, can be stable, can be analyzed, that actually has the right properties once it's injected into an animal, including a human, all of those other pieces to it.
I think all of the things that we're doing for the conditional biologics, they follow all the same kinds of rules of the things that we've learned for other kinds of biologic therapeutics. We've been, you know, it's been decades now that we've been working on different kinds of biologicals and we've learned so much, both how to test it ahead of time to predict if it's going to be good or not, how to design it, all of those sorts of things. So we bring all of that to bear. Now that said, these can be potentially complex molecules. They're not simple, potentially.
But I think that we know how to do that in the design phase. And so that is our responsibility in the early phases to make sure that it's something that we can make and produce and use.
Kevin Folta (18:51.107)
very good. But these are conditionally active. Are they conditionally inactive? Can you shut them off once they're on?
Neela Patel (18:51.577)
I think we're...
Diane (18:59.788)
Yes, depending on the mechanisms that's used for that conditionality. So the protease cleaved ones, you can't, right? Once that protease cleaves that, now you have an active cytokine wherever it is, you know, it's now active and it can become systemic. With what we're doing at Bonum, our mechanism is reversible, it's fully reversible. So when it's bound to the target that turns it on, it's on, if it comes off, it turns back off. And that is a really nice feature of the technology we've been working on.
Kevin Folta (19:29.421)
very good. Now this is really exciting because of reasons I stated earlier in the introduction, you know, new classes of therapies, being able to tailor the immunotherapy response. This is a big deal. And so we're talking to Dr. Diane Hollenbaugh and Dr. Neela Patel, both of Bonum Therapeutics. And this is the Talking Biotech Podcast and we'll be back in just a moment. All right. So there's a little bit of a break there. So we're doing good so far. This is awesome. Love it.
You're very good at this. Thank you.
Diane (19:58.734)
okay. Happy to take direction.
Neela Patel (20:01.745)
That's really good, yeah?
Kevin Folta (20:03.885)
No, no, you're doing wonderful. I've, I've had a few challenging interviews lately that are going to have extensive editing sessions and this one will fly right through. I love it. Okay.
Neela Patel (20:13.979)
Yeah, Diane's a pro and really amazing at coming up with examples that people can understand and that someone who's a little more sophisticated will get as well. So it's really good.
Kevin Folta (20:25.379)
That's a tricky line to walk. And, and, and, you know, I appreciate that a lot. It's your, your level is just right. So it sets the table for you, Neela. I think that's where we're going. let me take a peek here and see where we're going. Okay. No, very good. And, as usual, if there's any questions that, you know, I should ask you that are different from what's here, just stop me. Okay. Sure.
Neela Patel (20:37.095)
Perfect.
Diane (20:37.358)
You
Diane (20:49.282)
Can I just say, if you do want, if you want a little bit more about what is immuno-oncology versus other kinds of oncology approaches, can also throw, I can do that piece very briefly as well. Because you threw out immuno-oncology a couple of times and people don't always know what that means. It's up to you, I just wanna throw that out there.
Kevin Folta (21:00.985)
Sure, let's.
Kevin Folta (21:05.463)
Yeah, let's not it's not a bad idea. Let's on the backside of this here, talk a little bit more about that. And even though it's kind of out of order, it still makes sense. So let's just illuminate, you know, that let's dive in with that. So here we go.
Kevin Folta (21:24.851)
And now we're back on the Talking Biotech podcast. We're speaking with Dr. Neela Patel and Dr. Diane. I'm sorry. Let me start this again here. All right, here we go. And now we're back on the Talking Biotech podcast. We're speaking with Dr. Diane Hollenbaugh and Dr. Neela Patel, all about conditionally active therapeutics or conditionally active biologics and ways in which immunotherapies are being tailored to treat specific cell types.
One of the things that maybe came out from the first part of the talk was we really didn't dive too much into the immunobiologics and the immuno, you know, this class of drugs. And so maybe Diane, could you give me a little bit more on that? I what exactly are we talking about when we refer to this class of therapeutics?
Diane (22:13.806)
So when we talk about immuno-oncology, what we're talking about is finding ways to have the immune system recognize the cancer and get rid of it. the cancer cells, as they evolve, they have to have these mechanisms of hiding from the immune system or turning off the immune system. And what we're trying to do is to reverse that. And as you said, cancer cells, change all the time. So it's difficult if you have something that just targets one specific thing, then they change. But your immune system is
very good at adapting and seeing lots of different things in something it's trying to get rid of. That's what it does. And so if we can trigger this immune response, get the immune response to get rid of it, not only will you get rid of that solid tumor that you're seeing, but you also get rid of those cancer cells wherever they might be. So you get rid of all those other things as well, which is just really nice. And then if they start to grow again, your immune system's right there to take it back out. Because once it's seen it and knows how to do it, it'll keep doing that. That's what it does.
And so the immuno-oncology area is really trying to find ways that where we're training or re-enlivening or getting rid of the mask that the cancer cells are using so that your immune system gets rid of the cancer. And we're not targeting the cancer cell itself, we're driving the immune system, letting the immune system do that business.
Kevin Folta (23:31.439)
Yeah. And so just to clarify, you know, maybe if we think about chemotherapy as ways in which we're targeting cell division or checkpoints in cell cycle to limit the way cells divide, this is actually training the systems that are within the body already to recognize a barren cell division and a barren cell types that normally would be hidden because of the nature of cancer cells. Is that where we're going?
Diane (23:59.918)
Absolutely, that's perfect. That is a great way to describe that. Yes.
Kevin Folta (24:02.831)
Well, that's really cool. So when we think about this from a business standpoint and in the landscape of all the approaches that are being taken on, how many companies are currently in this space and what kind of problems are they targeting?
Neela Patel (24:18.631)
You know, there's of the ones that we can see and we of course know that in biotech there's often companies working in stealth mode, but there's about a dozen or so companies in the area of conditionally active biologics. And you and Diane have had some nice conversations around companies that use protease activated technologies. You also referred to ones that would be immunocytokines. So just
targeted but not on or off just it's only the getting it to the right address and of course for those Circumstances you now have a fully active theoretically cytokine that can be toxic everywhere so the companies that are in that space have found that they need to reduce the activity of the cytokine itself because otherwise even though it's
being dragged to the right place, it's being administered to your whole body and you're still getting the toxicity. So that's another bucket. And then there are ones where people are using pH or metabolites as a way to control the activity, either of the antibody or of a cytokine. So in round numbers, about a dozen,
It's an emerging field. There's definitely people in the clinic now. So far, there hasn't been an approved drug yet, but that's not because things are going poorly. It has to do with how young the field is. And we expect, I mean, even at the time that we've been a company, we've seen new entrants into the field. So we expect that this is going to be an expanding area.
Kevin Folta (26:07.791)
I certainly agree. think that there would be more and more because it's making the area of immunotherapies only more directed and specific and less toxic. So broadly speaking, if we go across the entire healthcare landscape, what's the market opportunity here?
Neela Patel (26:28.945)
The market opportunity will depend on the particular.
cytokine that you're using and where we already know it can be active and then we can also look and see where we believe it will be. In all of these cases, the markets are very significant, meaning that, for example, our lead program today, which uses interferon alpha, we believe that near, well, we know every single cell type in the body has interferon alpha receptors. So the receptor is present and we're
targeting it in a way that is to a target that is present in the majority of cancer types and at a high prevalence. So it's not like a lot of patients who are unlikely to respond will be dosed with our drug. So we think there's a lot of unmet need and we do believe that the cytokines that we're using and that others are using because others see the same opportunity that we do will really
be beneficial for patients.
Kevin Folta (27:36.303)
Well, know, I'm sorry, go ahead.
Diane (27:36.824)
From a, just to add a little to it too, from a broader class of conditional biologics, I we're talking about immuno-oncology and the focus of what we're working on, but from the broader concept of something that's conditional, that really can apply to many different state targets, many different therapy areas and needs beyond oncology even. And so we do think that there's, if you, you know,
the human condition, there's lots of things where having something that's targeted could be beneficial. And that's one thing that we've really been interested in is making sure that whatever we're doing also might enable people who might, we might want to go into different therapeutic areas, different disease states and things like that in a broader way, not just immunonecology even.
Kevin Folta (28:25.293)
Yeah, could you give me a good example of that? maybe, you know, autoimmune disease, seems like an obvious one or.
Neela Patel (28:30.855)
I
Diane (28:32.654)
Yeah, I mean, if we knew for a given autoimmune disease what things the immune system was responding to, we could turn off just that as opposed to the more, like, now what we need to use is a lot of broad immunosuppression. And some of it's somewhat targeted or directed at least a little bit in how the biology is. But if we knew for sure that this is what we need to turn off and we could send that to it, maybe just a really simple way to say, if I knew how to get
something as an anti-inflammatory just into the joints that were inflamed. Wouldn't that be lovely? That would be fabulous.
Kevin Folta (29:07.131)
And it seems like those kinds of targets are potentially there because biologically speaking, these cells should have specific targeting domains. Right. And so this is pretty exciting stuff. So let's go back to maybe kind of the business side of this. I know, I believe me, I like the science side, but the business side, we sometimes have to touch on a little bit is it's an exciting time for the field and more people are in the space, more companies in the space and
Diane (29:22.392)
Sorry.
Kevin Folta (29:36.219)
making generalizations is really difficult. But when you talk about your company, you talk about Bonham, how is the approach differentiated from other companies working in the same kind of space?
Neela Patel (29:49.074)
think the main ways in which we're differentiated is something you raised right up front is that we are targeted and we have both an on and off switch. And it's actually the same switch, which is quite convenient for us because as I mentioned, there's a number of companies working in the targeted space, but they don't control, they don't have an on off switch.
And then there's other companies who are working in the on-off switch space, but they're not necessarily targeting. And then there's ones like protease activated where, yes, it's off in the periphery when it's still intact, but after cleavage, that...
activated molecule can go anywhere. So, you know, in theory, you're reducing the amount of systemic exposure, but you're not really having a true off switch. So we do believe that our technology is differentiated and will offer patients a broader therapeutic index. So a bigger window between where you get efficacy and where you see toxicity.
Kevin Folta (31:03.727)
Let me do this, just kind of step aside here for a second. Let me, is there, so it you have an, the next question is you have an interesting origin story. Is that really interesting or like, I mean, isn't something that, well, I don't want to sound like an infomercial for Bonham, because I think that'll turn people off. So, so, so.
Neela Patel (31:25.147)
think I can talk about it from a make it generalize it as on the business side. If your listeners are not interested in sort of the how businesses are able to have product move forward and continue with the company, then it won't be interesting. But if they are, I can talk about it in a general way. And it really is not is not enough. It's not a commercial. Okay.
Kevin Folta (31:31.544)
Okay.
Kevin Folta (31:40.047)
Plus minus.
Kevin Folta (31:49.584)
Let's do it real short. Let's keep it real short though. It is, it is. So this audience is more about the technology more than the business side. And, uh, if you can hammer that out, we're cool. And then let me jump ahead. So you kind of already talked about the advantages of the dual body, dual binding antibody platform. So let me jump ahead the pipeline. Okay. So I'll go through, you know, tell me about the origin story and then we'll go ahead the pipeline. Okay.
Neela Patel (31:58.876)
Yeah, OK. I can focus it in a way that I think will speak for us.
Kevin Folta (32:19.727)
Here we go.
Kevin Folta (32:23.471)
And just by perusing the website and looking at other information, there really is an interesting origin story here. So could you tell me a little bit about how Bonum was founded and the roles of the good therapeutics team?
Neela Patel (32:37.127)
Absolutely. So it's a great question. We started as a company called Good Therapeutics, working with the same technology platform and developing it. And our lead program, PD-1, regulated IL-2, was of interest to several pharmas. And ultimately, we sold that.
program to Roche and we did it as an M &A. And what might be of interest is that Roche probably wouldn't have paid anything more for the whole company and our platform would not necessarily have been deployed widely. So we made the decision and Roche was actually quite happy to just get the product that they wanted. And then we spun out the platform technology.
All the employees became employees of Bonham the day after they were laid off from a good and the next morning they came in, they were Bonham employees. It was all very smooth. And what it meant was that we could continue to use our platform and make new drugs for patients. So it worked out, I think, well for all parties.
Diane (33:30.636)
Thank
Kevin Folta (33:48.369)
Are they still in your Rolodex?
Neela Patel (33:51.047)
Absolutely, Conversation's always ongoing.
Diane (33:51.086)
Always.
Kevin Folta (33:55.92)
Well, let's talk about that. mean, what are some of the other exciting parts of the R &D pipeline and their current status in that pipeline? You know, what is the lead program and why did you select that one to kind of lead this development of this type of strategy?
Diane (34:15.79)
So we have our lead program is, as Neela mentioned, our lead program is a stroma targeted interferon alpha. It brings interferon into the tumors. And we know interferon is this very powerful cytokine, and it does all the things that you want it would want within that tumor with respect to the immune system, the stromal cells, the cancer cells. And so, but again, we can't use it systemically. So it's perfectly suited for our technology where
we're taking it right into the tumor, it's off everywhere else. On in one place, completely off everywhere else. So that program really was one of the things that we do is we always try to look for places where the biology is well enough known so that we know what to do, so that we know what the need is and what it could be and how to test for that. And that one is perfect for that because we know that the interferon is exactly what you need in that setting. And we had just the right target to be able to target it.
Kevin Folta (35:14.445)
Yeah. No, no, I was going to jump backwards a little bit. So let me edit, edit, here. So, okay. So you're talking about interferon. Give me a little bit of a hint about what interferon is and why it's so important. Like, you know, of all the cytokines, well, what's going on with interferon? We heard about it in the late seventies as the cure for cancer. So give me more information about this and, and, you know, why it has deleterious effects on non-target cells.
Diane (35:14.588)
Prior to that, sorry, go ahead.
Okay.
Neela Patel (35:36.903)
Great.
Diane (35:44.056)
So it is, because it, like all the cells express the receptors for this, it can act everywhere. And that's partly because one of its functions is to tell a cell that it shouldn't be keeping on going. So it acts on all these different cells, but it acts in different ways. Within the immune system, what it is in the immune system, it's really a link between your innate immune system. So this is the part of your immune system that first reacts when there's, you you have a bacteria.
It doesn't know what it is. says, no, there's a bacteria. And it tries to recruit everybody else and all the other adaptive cells. And so that piece of that function, what it's doing is that it's stimulating all those cells that support your adaptive immune response. And when we talked before about immunoncology and what it is, that adaptive immune response is what we need. So what interferon does is it can signal to the cells that are part of the adaptive immune response, the cells that will actually kill the tumor cells.
But it also signals to all the cells that are, the set of cells that are suppressive to those cells, and it tells them stop being so suppressive. Don't do that anymore. Differentiate into something good. And then it also signals to the dendritic cells, where this is a set of cells that are necessary for showing the immune system what it needs to respond to. And what interferon does there is it says, there's something going on.
grab all this stuff and show it to the immune system in a way that makes it respond. And so that's what those cells do in response to interferon. So that's why within the tumor, all of those things are what we want to have happen. And interferon alpha is uniquely the cytokine that can do all of those different things.
Kevin Folta (37:23.129)
How does the...
Neela Patel (37:23.303)
And I would say we're really, you I just want to add on and say, I think we're really at a wonderful point in terms of the field at large. And I mean, scientific understanding of how the immune system works.
the mediators, the signalers, and so on, to be able to identify really key cytokines or other biology that can make a difference. Like there's enough precedent in the clinic to say, go this way because patients do respond, but the toxicity is not.
appropriate or not tolerable, it really does not work out for them. And we're able to really build on that in a way that I think has a potential to be transformative.
Kevin Folta (38:15.011)
Very good. All this makes so much more sense now. How does this, it's going back to the dual body or I'm sorry, come in, go back to this. Hold on. Sorry. I got to pull up something on the.
Yeah, got it. I will make sure I get it right. Okay. Yeah. Binding. That was the word I was looking for. Okay. So going back to the dual binding antibody platform, how does that enable something like the eye, the interferon alpha to deliver the right agent to the right target? And how does that make a therapeutic and you've kind of covered this already, but how does it make it a little more safe and
Diane (38:31.991)
biting anybody.
Diane (38:38.382)
You
Kevin Folta (39:00.685)
are powerful. Let me say that again.
Kevin Folta (39:11.247)
Okay, here we go. Okay, so we've covered a lot of this already, but when we're talking about interferon alpha and how that's being used, how does the dual binding antibody platform play a role in this and how it allows interferon alpha to deliver the right agents to the right target, creating a very powerful therapeutic in the right place.
Diane (39:36.216)
So the way our platform works with dual binding antibodies is this. So antibodies, can bind to a protein and block its function. So we can make an antibody against interferon that now keeps interferon from being active. And so if I have that, that's not going to be active anywhere else because it's stuck on this antibody that keeps it from binding to its receptor. What we do is we make a dual binding antibody, meaning that that antibody can
also bind to something else. And so in our example with this, our lead program is LERK-15. So it can bind to interferon and be a blocking antibody, or it can bind to LERK-15, but it can't bind to them both at the same time. So then what we do is we take that interferon and we create a tether, just a linker, and we link it to that antibody. So now it's linked on that antibody, that is, it's blocking antibody. So it's off.
goes all around the body anywhere you want it to go. It stays off because it's stuck to its blocking antibody. But if it gets to where its target is, now that antibody is bound to that target, that interferon is free to do its business. So now the drug is bound to the cells we want it to be active on, tethered with this very active interferon right there. The reversal piece, if it comes off,
It just binds again because it's just a blocking antibody.
Kevin Folta (41:02.435)
Yeah, and then this is what is such a pivotal part of this particular technology as an amino therapy that can be delivered to the right place. And just by it's, it's, this like, this is a physical, change in the molecule, right? When one binds the other is loose to interact. Is that what's happening?
Diane (41:22.742)
It's really just a competitive binding. So when the antibody is bound to one, it's covering up the site for binding to the other. So once it binds to LERK-15, it's not able to bind because it's now bound to LERK-15, it gets in the way. It's just a competitive, straight up a competitive binding.
Kevin Folta (41:40.355)
and it has more affinity for the, it has more, here let me jump in real quick. So it has more affinity for the receptor on the cell than it does for its ligand for the interferon alpha. So when you bind the receptor, now that interferon's free to interact.
Neela Patel (41:40.911)
Dan, don't know if you... Yeah, yeah, I just guess you... Keep going, sorry.
Diane (41:59.276)
Yes, with its receptor. Exactly.
Kevin Folta (42:01.456)
Perfect. And then, Nilo, you want to jump in?
Neela Patel (42:03.995)
I was just going to say Diane might want to talk about the fundamental insight that Bonum and Goode were based on is the fact that an antibody can actually bind two things. And I don't know, Diane, if you want to elaborate a little on that.
Diane (42:15.758)
Yeah.
Kevin Folta (42:20.163)
Yeah. So is there a question I should ask you to lead into that better?
Diane (42:20.386)
Yeah, is that okay?
Diane (42:25.198)
So maybe even just to ask a dual binding antibody, because antibodies are usually bound to just one thing. We always think of an antibody one to one.
Kevin Folta (42:32.543)
good idea. All right. All right, here we go. Well, throughout this entire discussion, we've talked about dual binding antibodies, but antibodies by definition, at least in my naive understanding, is that they have one good binding site. So what's happening here?
Diane (42:52.27)
So absolutely as an antibody person, we always think of that. antibody binds, one antibody binds one thing and that unique specificity is one to one. But the fact is that the binding site of an antibody is big enough that there's plenty of room for us to create binding sites for more than one thing. So in our antibodies, what we do is we just take advantage of that fact that there's enough real estate there to have two distinct binding sites for two distinct things that overlap like this.
Kevin Folta (43:22.669)
Now this is all good stuff and you know the thing for me is I get so excited when I hear about exciting new ideas and new technologies, especially in the area of immunotherapy that can solve these problems. But how do you envision development of this particular product type, drug type, with a timeline and ultimately be able to proceed to the market.
Diane (43:46.094)
So that's where in drug discovery and development, it's the development of an individual agent is all about what it does and the properties of that specific thing, not by what technology it came from. So in that sense, what we have is we have a drug that we have a very clear understanding of the in vitro properties, as in how much does it take for it to turn on, how much does it take to turn off.
And we'll do all the same things you would do with any other therapeutic, which is to do all this modeling between in vitro and in vivo data, toxicity data, concentrations, all of those things to get an understanding of where do we start in the clinic? And then what else do we look for in the clinic? What other biomarkers might there be to be able to follow? And in that sense, this is no different than any other therapeutic where we start from what does it do?
How do we assay for it? What do we expect it to do? What happens in the patient? How do we learn from that for where to go next?
Kevin Folta (44:45.987)
Yeah, it's it.
Neela Patel (44:46.075)
We don't really anticipate timelines that are different, as Diane is saying, than for anything else. And because we think really carefully from the very moment we start on a program about being able to manufacture it at scale and have it be stable and so on, we don't anticipate that there will be any particularly slower pieces in preclinical development. So we think our time tomorrow
should be should be similar honestly.
Kevin Folta (45:19.727)
Well, what about possibilities to accelerate that? It seems like a lot of companies are crawling over each other to be the newest and best technologies and, you know, take advantage of collaboration, for instance, with companies that are developing the best new ideas. And so what is the current environment like for financing and collaboration?
Diane (45:23.469)
You
Neela Patel (45:42.94)
Financing for privately held companies, challenging collaborations, very much appreciated and an active area both on the pharma side and on the biotech side. And ultimately, we as Bonum do not imagine that we will run pivotal trials, in other words, phase threes where you're enrolling large number of patients and it's very costly and there's a kind of infrastructure you need for that.
So we not only are interested in collaborating as Diane alluded to earlier to make new molecules, for example, in autoimmunity or to treat fibrotic conditions or metabolic conditions. We are also always looking at partnerships for pharma who would then take our molecule and
get it through the last part of development and commercialize and sell it. So you're quite right that we're going to, we know we're going to need those partners. We talk to them all the way along so that they, you know, when we're ready with a data set, they're like, I remember this was a project we're really interested in. We really liked the science. It makes sense. Now you've got something that really is at a milestone. We're interested in, in talking about a transaction.
Kevin Folta (47:06.535)
And that's all good. You know, every, and I would assume that that would be the case that there's folks who have the infrastructure to accelerate your work. But can you comment on the idea of having a biotech company with a cool idea that looks like it's working, that you have good preclinical data? What's it like doing that in the current environment?
Diane (47:28.12)
challenging. So challenging is maybe the way to say that. And frustrating might be part of it as well sometimes. But I think that one of the things that we learn in drug discovery just in general is resilience. There's always headwinds. There's always things, hurdles. And the way I look at it is that this is just another hurdle that our molecules are going to have to get through. And we'll find a way.
Neela Patel (47:29.127)
Yeah, I think challenge.
Diane (47:57.43)
I think that for me, for what we're doing, I believe very strongly in the biology of what we're doing that we're creating something really valuable and it will find a way. We will find a way for that to come forward, even if it's challenging. That's just how it goes.
Kevin Folta (48:12.911)
Well maybe I could throw one last question to... I'm sorry, go ahead, go ahead, Nila.
Neela Patel (48:12.999)
And I don't think it's really different. It's not different in pharma. I mean, you mentioned biotech, but it's actually not different in pharma. Both Diane and I have multiple experiences where a program dies eight deaths, and on the ninth time is when it gets through. And so you just have to know that you've got to keep pushing forward and being persistent and resilient, because this is not different.
Sadly, than it is anywhere else. It's normal.
Diane (48:44.322)
Especially when you're moving into a bit of a newer area, there's always that resistance. There's always that, well, I haven't seen this before, so it must not be right. Well, you haven't seen it before, but it's awesome. So it's hard to do that piece. And that happens like no other. That happens within a big company. It happens in little companies. It's just human nature. It hasn't worked yet. Well, the key word there is yet. We always have that word, yet.
Neela Patel (48:56.199)
you
Diane (49:10.914)
So there's always that challenge, especially moving into a new area, a new space, or a new technology. The need is still there. And one thing I think that always accelerates a program is as soon as you get a little bit of good data, you get some clinical responses, you get some interest, that'll really accelerate. Sometimes in a way, getting started is the harder part. And then once the molecule starts to show what it can do,
brings its own momentum.
Kevin Folta (49:42.928)
And this really brings me to the question that my guests usually hate because they don't have a crystal ball, but I always asked a crystal ball question. And that is, what is the most exciting part about the future that you think this class of drugs might bring? And maybe I could start with Diane and then go to Nila.
Diane (50:03.637)
For me, what it does is it opens up areas of biology that we can't manipulate any other way. So we've known that there are certain cell types, certain biology, certain things we want to be able to do, all the way back to IL-2. We know IL-2 does really good things, but we can't harness it. We don't have the tools to harness it. And now what we're doing, and we're developing these ways to actually harness these really powerful biologies in this really targeted ways that I think there's just so many opportunities
to be able to create therapeutics that'll really make a difference.
Kevin Folta (50:37.007)
Now, Neela, what do you think?
Neela Patel (50:38.855)
I agree with Diane. The excitement for me is...
that we really have the potential for complete responses, durable complete responses, which is equivalent to a cure in sort of, know, ordinary parlance, right? And not only, not just for a few patients, but because these mechanisms are universal, really the applicability is for many, many patients to benefit. And because I'm a scientist by training,
I really genuinely believe the benefit for the patient will lead to financial benefit for investors, you know, whoever spent the money to get the thing to the market and is selling it. So I feel like if you lead with the science that way, you'll always come out in the right place on the other side.
Diane (51:38.22)
And that ties to something that you started with, which is that, you know, if you're on this planet long enough, you've been touched by cancer. You, someone you know, a loved one, a family member, friends, you're touched by that. It's out there. And so having things that can treat that, I like to look back at how, you know, 20, 30 years ago, there were cancers that were considered, you know, really bad, a death sentence and things.
Kevin Folta (51:38.255)
Well, very... I'm sorry, go ahead, Dan.
Diane (52:06.54)
And there's some now, I had a family member diagnosed with cancer and the question to me was, is it a bad one? It's like, well, now, today, not so much. 20 years ago, yes. So that is the thread that we look for. I want someone to be able to say, is it a bad one for all of them? Not so much. We have something. That's the goal. That's what we're after.
Kevin Folta (52:31.343)
Well, this is all very exciting. If people want to know more about Bonum Therapeutics, where do they look on-
Neela Patel (52:38.535)
BonumTX.com, come on over. And we have both information about our programs and also links to our presentations, publications, and more publications to be coming in the future.
Diane (52:41.856)
You
Kevin Folta (52:53.667)
Very good. Well, Dr. Diane Halenbaugh and Dr. Neela Patel, thank you so much for joining me and do me a favor and please let me know when the big breakthroughs happen because I'd love to talk about them here. This is just a seed we plant and then later on we'll love to follow up with how this is changing everything. So thank you very much for your time.
Diane (53:15.054)
Thank you.
Neela Patel (53:16.071)
Thank you so much, Kevin.
Kevin Folta (53:17.823)
And to live the listeners, thank you very much for listening to this week's Talking Biotech podcast. Get excited about more therapies using novel approaches. And I know if you go back through the archive, we've talked about these for a couple of years, different ways in which we're trying to solve the most insidious problems in human health. This is just a different approach that together with many other approaches may lead us to very good therapeutics in the future that can help solve some of the biggest problems.
the human condition. Thank you for listening to Talking Biotech podcast and we'll talk to you again next week.