PEGS-The Chain Episode 87

July 14, 2026 | Most ADCs today lean on the same Topo-1 payloads—and resistance is catching up. Jack Elands, Ph.D., founder and CEO of Adcytherix, speaks with host Rakesh Dixit, Ph.D. about what “next-generation ADCs” should mean if we care about patients, not just pipeline counts. Their conversation gets specific about where differentiation comes from: novel payloads with new mechanisms of action, better therapeutic index choices, and smarter design decisions that reduce the toxicities that make patients quit therapy early. They also pressure-test the hype around bispecific ADCs and dual-payload ADCs.

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Adcytherix


GUEST BIO

Jack Elands, Ph.D., Founder & CEO, Adcytherix
Dr. Jack Elands brings extensive ADC and biotech leadership experience as founder and former CEO of Emergence Therapeutics, Talix Therapeutics, and has also served as CEO of BliNK Biomedical, co-founder and CEO of Amakem, CEO of Vitec, and co-founder of MImAbs.

MODERATOR BIO

Rakesh Dixit, Ph.D., DABT, President & Founder, Bionavigen Oncology, LLC and Regio Biosciences  
Rakesh Dixit is an accomplished executive, inventor, and scientist with over 35 years of success with top biotechnology and pharmaceutical companies, including Merck, Johnson & Johnson, and Medimmune - AstraZeneca. Currently, he is president and CSO of Regio Biosciences and Bionavigen, LLC. He is a board member of Regio Biosciences and a key member of multiple scientific advisory boards. Rakesh is also a chief adviser and consultant for more than 20 companies worldwide. Rakesh has unique expertise in developing biologics and small-molecule biopharmaceuticals. His areas of expertise include discovery, early and late preclinical development, safety assessment, DMPK, and translational sciences.

Rakesh conducted extensive graduate and post-graduate training in pharmacology/toxicology–biochemistry with both Indian and USA institutions (e.g., Case Western Reserve University, Medical College of Ohio, University of Nebraska) and is a diplomate and board certified in toxicology from the American Board of Toxicology, Inc. since 1992.


TRANSCRIPT

Welcome To The Chain

Announcement

Welcome to The Chain, the podcast exploring the lives, careers, research, and discoveries of protein engineers, scientists, and biotech professionals. We look at the impact their work is having on the field and where the industry is headed. Tune in to stay up to date on the newest advancements and to hear the stories that are impacting the world of biologics.

Meet Jack Elands And Adcytherix

Rakesh Dixit

All right, so good morning, everyone, and good afternoon in Europe. My name is Rakesh Dixit. I'm a toxicologist and translational drug development scientist with you know multiple years of experience over 35 years in biologics, ADCs, biospecifics, peptides, and all the advanced therapeutic platform. You know, in my previous role at AstroZeneca and at J&J and Medimmune Company, I have been actively involved in in multiple areas, biologics RD and small molecule drug development. Enough about me, but in this podcast, I'll be speaking with the leaders across biotechnology. And and with that one, I'm so delighted today to welcome Dr. Jack Elands. Jack is a founder and CEO of Adcythrix, a next generation ADC company that is focused on developing highly differentiated ADCs for cancer and other diseases with high end medical need. Very quick about Jack. Jack is a highly experienced biotech entrepreneur and ADC leader, I will say. He previously founded and led Emergence Therapeutics. I worked with him for that company as well as an advisor. And this is an ADC company that was acquired by El Aleli in 2023, and now have brought together a seasoned team, created a seasoned team, including me as an advisor at Adcytherix to build the company as a next generation ADC design platform, as well as ADC development company, is advancing multiple ADCs in high and medical need area.

Rakesh Dixit

And since its launch, I've learned to say that with Jack's credit at Scythix has attracted strong international investor support, including over $30 million seed finance, 30 million euro seed financing and our over 105 million dollar Series A funding for ADC pipeline. Jack is brings a rare combination of scientific vision, company building experience, and deep knowledge of ADC backed development. Today we're going to discuss the evolution of ADC field and what is needed to create truly differentiated next generation ADCs and how at SiteSix is positioning itself to developing these comp this highly differentiated, comparative, highly competitive oncology ADCs. So, Jack, welcome to the podcast. Before I get started, do you want to say a few words about you or before I get into questions?

From Neuropharmacology To Biotech CEO

Jack Elands

Yeah, well, first of all, thanks, Rakesh, for the introduction. Good morning, good afternoon, depending on where you are. Good afternoon for me. I'm based in Brussels. Yeah, I'm I was trained basically as a neuropharmacologist. So it's been you know it's been a long road to end up in in oncology. After having spent a number of years doing pure academic research, I made a jump to the pharmaceutical industry at Marion Meraldao in Strasbourg, now better known as SAFI. And that center basically was a center for development of drugs that you know central nervous system-based diseases. After a while, I got involved in the automation for drug screening, developed data management because the hand systems couldn't cope with it anymore. And because of all that work, I ended up in redefining with the team the lead generation and discovery effort, and that made me view a larger, a much larger piece of the business than ever before as a scientist. And from that moment on I could only live in the biotech world because it was it was too difficult to go back and to work in a very limited segment within the industry.

Jack Elands

So I effectively joined the the various biotech companies and ultimately ended up launching my first company. This was in 2010 in Belgium, a company called Amakem Therapeutics, where we developed, this was probably the closest to my neurology background or neuropharmacology background. We developed drugs to treat glaucoma, so intraocular pressure. We developed that up until phase two and then sold the business to a Korean group. And then from there on in 2015, I basically made a jump to antibodies and oncology. I took on the helm of Blink Biomedical, an amalgamation of Blink therapeutics out of cancer research technology on the one hand, and the antibody business from Valneva on the other end, that became Blink Biomedical. From Blink, I'm still actually involved with Blink because there is some deals that create long-term revenues that I'm still administering, but it's a very small piece of my activity. At some point, we were asked by Kirma partners in Paris, an investor in Paris, who were invested also in Blink, whether I was interested to take on a mandate to look at Nectin 4 as a potential ADC target. At that time, you know, CGIN was already developing Enfortima Phototin, later better known as PATSEF, and now on the market, of course.

Jack Elands

And after taking a good look at that, we thought, yes, it's a it's possible to develop a best-in-class based on the proof that Enfortima Phodotin had given that it would actually it actually is a good drug to treat bladder cancer. So we we had a collaboration with the Center of Cancer Research in Marseille, together also with the local cancer hospital, which is one of the more most renowned cancer hospitals in France. We set up a company that was a basically having a French German company with a holding in in Germany, but with the active the biotech development area in in Marseille, in France. And we developed a DAR-8 exoticon-based Nyctin 4 ADC that was the best in class after PATSEF. We never made it to the clinic, right before we were we had already filed a CTA, and then Lily basically knocked on the door and acquired us before we were able to to go into the clinic. That was in August 2023. Unfortunately, Lily has just announced that this drug has been stopped. Lily was developing two Nectin 4 ADCs with the Exatcon or Exatcon-like payloads, and they have stopped ETX22, even though I know from having spoken to principal investigators that the drug actually is very, very efficacious and has a very high level of objective response rate. Lilly acquired us in August 2023, and they required me to step down. I didn't feel that the business was finished and that there were still lots of things to be done in the ADC field. So I got together with Pontifax, Ran Nusbaum, and basically asked them if they were willing to help me to set up another company. Rand basically told me that he was about to ask me the same question. We then spent a couple of months to work out the business model, make sure that the people that I wanted to bring along were freed from any any emergence or Lily background. And then in April 2024, we started AtSetherix.

Building A New ADC Company Fast

Jack Elands

The idea of Adcytherix is to build ADCs with payloads that can overcome resistance that is created by treat by treating patients with either jubilin or topoisomerase inhibitor one-based ADCs. But when we started the company, we had basically the idea, but not a real good sense of how to go about it. So we built the company around an asset that is not unlike ETX22 following PATSEF. So here we don't yet disclose the target, but here we're basically following a tubulant-based, tubulant inhibitor-based ADC, where we are developing a best-in-class targeting a target that is now better known than when we started, where there is a first-in-class ADC being developed in late-stage clinical trials, and where we know very clearly that we will be able to develop a best-in-class, a real best-in-class. We started with a 30 million euro seed round that was led by Pontifax.

Jack Elands

We brought in RA Capital, KKR through their DORM bio platform, and WUSHI made an investment direct and via Pureios. And then in October, we finalized the Series A of 105 million euro, where BPI France, Kirma, Andira partners, Angelini Ventures, and Amoon, as well as Surveyor from Cadell joined us. So now we're well funded. We as I mentioned, we started with the DEAT program where we're developing the best in class. We do that based on a DAR4 exat econ type structure. And we were able to dose the first patients within two years since the start. And so we're in early dose escalation at the moment. We've just done the first dose level, and we should have our dose escalation meeting mid this month. So it's exciting times. But as I mentioned, the key thing that we were interested in for at Cytherix is really looking at novel payloads.

Why The Field Needs Novel Payloads

Jack Elands

And one of the first payloads that we looked at is from the family of trabectadin and lurbinectadin, compounds developed by Pharmamar and on the market to treat various different indications. We went for Lurbinectadin for a variety of different reasons, and lurbinectadin is basically approved to treat small cell lung cancer in the US, and it's in clinical trials for a number of other indications. The mechanism of action of these payloads is very different than from tubulin or topoisomerase 1 inhibitors, and that makes them ideal candidates to follow on to treat patients that have developed resistance against the current generation of ADCs. People that with knowledge in the field, it will not have gone unnoticed that almost every ADC that's being developed today is equipped with the topoisomerase 1 inhibitors. The first ones were, of course, NHER2 and the rest of the DIEC stable using the Rixtecon, but then a large number of ADCs were developed with Exitcon or Exitcon derivatives. And the amount of ADCs that are being developed in this field with topo 1-based ADC payloads, it's just too much. Patients will have will develop resistance. So it's critically important that we follow on with payloads that can overcome that resistance.

Jack Elands

And that's what the rest of the pipeline of the company is about. We've just put into development the first, which is trestizomap using Lurbinictidin. And there we're basically, amongst others, going after patients that have been treated with NHER2 and that have developed resistance. I think if you look at the latest literature in this area, we see more and more reports that patients treated with NHER2 actually do develop resistance. And that oftentimes this resistance is related to changes in the way that the topoison rase one inhibitors can work. It could be efflux pump upregulation, it could be changes in the topo isomerase gene point mutation so that these inhibitors don't bind so well anymore, etc. etc. But it's sometimes also the target. There's a very well-known example of drop point mutation that takes us off the membrane. And internally internally in the cytoplasm, you see accumulation. But the majority of cases of inhibition sorry of resistance are really about the payload.

Career Turning Points And Value Creation

Rakesh Dixit

That's fantastic. and and thank you, Jack, for you know, you know, educating us with your journey in the up to the ADC field here. You have a long career in RD. So the first question that I have for you, Jack, that what actually sparked your interest in science and led to the biopharmaceutical RD over your 30 years or more longer career in biopharma, what moments most shaped your path? You know, like moving from the neuropharmacologist to the antibody to the ADCs? You know, what were the critical, you know, you know, time points, you know, in your career where you said, okay, this interests me more now than the other ones, and you know, that guest stuff.

Jack Elands

Yeah. Good question. I think I considered myself a fundamental academic scientist. anything that was you know, like drug development, that wasn't that I wouldn't say it wasn't science, but that was not what I was interested in. The change really came when I joined Marion Aldao. I was I was asked to set up certain activities only to find out that when I was there, I was basically replacing a person. So we're talking about the early 90s. That was still money, it was not an issue. And so I was basically replacing a person who had left and that nobody wanted to work with. And so the first reaction was do whatever you want, just don't get us involved. That I found something that I couldn't understand. So I started wandering around, talking to people, and basically found out that the chemists were complaining that you know the molecules that they made didn't get tested. So I said, Well, we can fix that. And so I started building a profiling screening platform that grew to a center that all the four research sites of Mary Melda would submit as samples to, and we built a lot of automation around that. And it was a at the time, it was such a logical step for me to not do something that nobody wanted, and yet look at how people needed things and where I could be useful. It was almost like an automatic breaking away from my academic mindset and becoming very in industrial, very very focused on adding value.

Jack Elands

And not, I think it wasn't so illogical that once I saw the broader business aspect having been in this lead generation optimization effort, that you know, I became more attracted to the whole idea from starting in very early in conceptually you know developing a program to develop a drug, and then also you know looking at at the end, the financials, the marketing, and the business development, etc. That's why I went to biotech. But again, initially my biotech efforts were very focused on they were very focused on um on small molecules, and only later I started to get more interested in in antibodies. I think my my the change from Amachem to Blink was one of having seen the power of biologics and looking at a a more practical way to develop drugs faster than with small molecules. And it was it was an idea. I you know, I can't say that all biologics are developed faster, but it there are I think there are certain ways to to skip things and do fast do things faster with biologics than you can do with small molecules. And um with Blink we went a long way. We developed the CD47 asset that we then ultimately sold to to Gilead. and we did a back license to Genmap. GenMap has for a long time been developing by specifics based on the C D47 asset, but I unfortunately never was able to get this into the clinic myself, or myself, but at least directly, in contrast to the glaucoma program that we you know we developed up until phase two. And so the idea to leave the because C47 is essentially in you know it's an immuno oncology, and immuno oncology is it's not an easy field. It's a very delicate field with lots of intricacies on how proteins are being regulated, the immune system is is almost immune for changes and manipulation.

Jack Elands

So the idea of developing or looking for an ADC where you use the antibody basically only as an address to find the cancer target and then deliver the bomb to kill it, I thought was very attractive. And it really was something that I wanted to put my weight behind. We spent a lot of time, I'm talking about Xavier Preville and myself to build a business clause. This is actually where you and I first met, and where we laid out a development plan up until the moment that we could execute it and then started the company. So it's a gradual process of having been very opportunistic at Marion Meraldow, not wanting to do something that wasn't useful in the context of a pharma company and looking for the best way to make myself useful. That was probably the biggest change in my career that I can think of. The others were smaller changes, even though you know they got me where I where I am right now and they were important. Let me add one thing that I often talk about with new CEOs or soon-to-be CEOs. I actually have spent some years in in strategic marketing and business development, the commercial business development, so selling stuff. It's an incredibly valid experience to do that. I think most of us that are in the biotech world, we don't have the a good sense of what we're doing when we're raising money, when we're talking to investors. And the commercial business development background for me has been an absolutely great teacher on you know how best to look at that, how to control that process. That is something that came over time. It's not been one moment, but if anything has shaped my career, it's also that. That the commercial business development background has really been very, very, I wouldn't even say helpful, but critical in getting me where I am today.

Patient Impact As The North Star

Rakesh Dixit

Yeah, this is a fantastic, great advice, Jack. And I'd 100% agree with you. And and looking at this, you know, given that you have worked with lots of different programs, lots of different things you have done in your career, even in the areas where nobody wanted to go, you went there, you know, took some risk in your, you know, in your career. Of all the programs that you have worked, you know, in your career, which project or experience you felt that's most rewarding, has been most rewarding scientifically, professionally, or personally? Not necessarily on the money side. I'm just talking about more from it, something that you said, you know what, I feel good about this, you know. And both scientifically and professionally and personally.

Jack Elands

Yeah, yeah. No, it's a very valid question. And you know, I can't ignore the fact that it's good to develop a drug to treat patients that have glaucoma. But nonetheless, there are drugs that can treat glaucoma. So there's there's opportunities there, you can do it better. But in oncology, I think it's different. You're not okay, you can do things better, but ultimately you're you're helping patients to live longer and ideally under reasonable quality of life conditions. Correct. And I think for me, it's the major reason that after emergence I wanted to continue. It's just the focus on being able to help patients that is really very important. And I also tell this to the team, to the people in the company, I tell it to my investors, I tell it to other investors, that our focus is really not to bring value for investors, but to bring bring value for patients. And if we bring value for patients, all the rest will fall in line automatically. And it's that idea that you know patients who I'm I'm talking now about outside virus, but it's in general. But if you think about a patient who's being treated for breast cancer and then and her term no longer works, these women have no option left. So it's exciting and and and and really reinvigorating for a person like myself to be able to work on this and to develop drugs. So the more I get along, actually, the more I find it satisfactory because the more you learn, the better you can hone in on the diseases where patients need new drugs most. And of course, in oncology remains a field after all, whereby it's basically a question of life and death. And in many cases. So if you can have if you can make a difference there, yeah, it's it really is personally is very it's it's very important to me.

Rakesh Dixit

No, I fully agree with you because I think the question of resistance is is coming up a lot nowadays, despite the fact there will be people saying, Well, why do you want to develop another Hart to ADC? You know, what's what's the point when there are you know maybe 30, 40 LED ADCs, you know, targeting HAD2. But your concept or your strategy of developing an ADC for resistant patients, you know, patients who are not responding to current HA2 therapies is is really great.

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Ethics, Toxicity, And Quality Of Life

Rakesh Dixit

And since I'm a toxicologist, as you know, I will have to have that question, this question, the next one. So, to me, how do you balance the excitement of breakthrough science, breakthrough ADCs, with the ethical duty that we all have to protect patients from the harm? You know, what what we need to do either preclinically and clinically to make sure that we are not harming undue patients, patients unduly without without giving them something in return. You know, I mean With the cancer therapy, we all know there will be toxicities. But at the same time, we want to give them more benefit than the than the than these than the toxicity, because these toxicities also affect the quality of life for patients, you know. Because there is no there's no point in saying, okay, you have two months extra or five months extra to live with on my drug, but your life will be miserable with all the toxicities. You know, a good example is PATSA, where patients suffer a lot from peripheral neuropathy and you know, newtopenias, infection rates, and all this stuff. Skin, not to mention skin toxicities. And I think what I liked when I was working with you on the nectin-4 program, you did something to prevent that, you know, by developing a more differentiated nectin 4 ADC. So I would, yeah, so more elaborate on a little bit more on

Reducing Skin Toxicity In Nectin-4

Rakesh Dixit

that one. Yeah.

Jack Elands

Yeah. So let me start on Nectin 4 and then move on to what we're doing today. So yeah, nect if you look at PATSEF, it was obvious from talking to the clinicians that 's it causes peripheral neuropathy. But it the most important thing of PATSEF, which is a negative differentiator, is skin tox. And but by when talking to the clinicians, and in particular to Jonathan Rosenberg and Sloan Kettering, he said, Jack said the skin tox may not be that bad, but it makes patients decide to stop being treated. And so that's bad. And that needs to be fixed. So what we did is we at the time we didn't know how, but we felt it was important that we develop an AD an antibody that would bind to nectin 4 on the cancer, but not on the carotenocytes in the skin. We didn't know how to do it. So we basically put together a functional screen whereby we screened the antibodies both in the cancer, in the model of course, and then on freshly isolated carotenocyte from human skin. And we found antibodies that did the job. It goes maybe a bit far to go through the scientific explanation, but you know, we have two basic theories of of why this may work these days. And then we went through the testing of what became ETX22 using that specific antibody, and we've never found an instance of skin tox. I threw the grave pan, you know, because we have no formal official communication, it appears that ETX22 has never caused skin tox. And that, of course, is is very important.

Jack Elands

So I think there with the Nectin 4 ADC, we did our best to avoid skin tox, and it seems that we've been successful. When we started at Cytherix looking for novel payloads, I basically defined a number of rules of thumb to select novel payloads. One was they shouldn't be too potent because we know that the over the ultra-potent payloads, they don't they're not manageable. The other is that it shouldn't, you know, it should also be potent enough. I don't want something that is a lot less potent than the Ruxticon. But I think the most important rule that we put together is let's find the payloads from drugs that are already approved as anti-cancer drugs. And if you pick those, you actually do, and lurbinectin is one, it's being used for the treatment of small cellular cancer in the US. You have a payload with be it a small, but with a payload with a therapeutic index. The other payloads that we're using today, they cannot be used as a standalone drug in men. They're too toxic, so they have a negative therapeutic index. Now we have a payload with a therapeutic index that's positive, even if it's small. So I think we know that there is a dose that's I'm not gonna say that it's you know nice, there are toxicities, but it's a tolerable dose. And so we should be able to get to an ADC with a dosing regimen where the toxicities are lower than with the most of the toxins that we use these days. It's it's the goal, it's part of what we want to do, and and we're putting it in place as we speak. Lurineicin is a good example of that. We have other payloads that are slightly less advanced and that I can't disclose now, but there's one payload in particular that doesn't cause cytopenias.

Jack Elands

Now, if this payload would work and we would not have any neutropenia, you know, that means that patients, when they're treated and they they there's no risk of root neutropenia, they can just go home. They don't have to stay hospital to combat infections. So these are these are things where I think we can really look at, on the one hand, the benefit of an ADC, you know, with a very much more targeted therapeutic treatment rather than the earlier generations of cancer therapies, but then also you know, combining it with compounds that are that are known to work, first of all, against cancer and that have a therapeutic index, and hopefully, ideally get an ADC that is more tolerable and that therefore can be dosed longer, and that can therefore help patients for a longer time. Because as you, as much as you know, patients do not always stop an ADC treatment because of progression of the tumor. They may just be fed up with GI tox after having been treated with a topo 1-based ADC. They may be fed up, like in the case of a PATSEF with skin tox. The toxicities that ADCs cause often are a reason for patients to discontinue treatment. And that is, of course, a problem that needs to be fixed.

Rakesh Dixit

No, I think that's very well said, Jack. And I just came back, you know, a couple of weeks back from the ACR meeting, and there has been a lot of discussion in the ADC field on the novel payloads. And just not a novel payload for the sake of it. It's the novel payloads that can maintain reason, you know, pretty good efficacy in patients, but but not increasing toxicity, in fact, decreasing some of the adverse effects that are not well tolerated by patients, because you know, this just not a toxicity, it also affects the quality of life of patients. And as you said, that that quite often is the major reason why patients don't want to, you know, take anymore that drug. I mean, if I had cancer and if I cannot get up in the morning and you know, close my buttons, you know, or continuously seeing, you know, on the antibiotics for the infections or something else, I think I will consider switching it to some different therapy. And I think to me, the quality of life is directly linked with the with the toxicity of ADCs, as well as, of course, the cancer itself has got its own toxicity problems, you know, because of the you know, cancer effects not only it affects a lot of physiological functions in the body, and that can also impact, like especially getting, you know, being tired all the time and all this stuff. But but definitely on the safety side, I really like that approach.

Choosing Safer Payloads With Therapeutic Index

Rakesh Dixit

So coming back to the future of ADCs, okay, because that's what I want to focus today in this this podcast. That in your experience or in your thinking, what do you think is the which therapeutic ADC modality the thing will define in next decade and why? Because I came back from a from the ACR meeting and I saw a very crowded ADC field. And actually I wrote something in the in the LinkedIn that it's not the it's not the ADC field is crowded, it's crowded with very undifferentiated ADCs. You know, what which I meant by me too, okay. This person has it, so I need to have this, you know, that this company has it, so I need to have it. Like a good example is like, you know, you know, Hart2 space, BCMA space, you know, B7S3. And I looked at a lot of these posters and said, you know what, what's new? Okay, what exactly new you are doing? You know, did you did you invent a new payload or or or somehow you think this will change the the the differentiated enough? And and I did not see that. So what I'd like to hear from your point of view, what do you think the next decade in the ADC field will come? Because a lot of people ask me, you know, that similar to the checkpoint inhibitor therapies, PD1, PDL1 based, you know, things went at the peak, and now nobody wants to invest much money in those therapies because they just don't see differentiation. You know, they say, how many, how many PD1s we can develop, how many PDL1s we can develop? And same thing we are seeing in biospecifics as well, where you know, almost every single week I see somebody developing another BC, BCMA, CD3, you know, engage, T cell engage, TCEs, you know. I mean, how many it is it really helping patients or are you just making a Me Too drug? So the question is what do you expect? What will happen to ADC field in let's see next 10 years? Where you think we'll be going? So just about to hear your thoughts,

A Framework For Sequencing ADCs

Rakesh Dixit

you know. Yeah.

Jack Elands

Yeah, I think in general, Rakesh, but let's take you know, PD1, PDL1 for an example. The the development cost is so high that it is actually useful that a number of companies work on PD1, PDL1s and then have you know various different clinical trials. Because I don't think there would be as much power and push for extending the boundaries of the potential treatment if it was done by only one company. But there is, of course, a cap on it. At some point it becomes counterproductive, and you could actually ask that it's no longer ethical either to invest so much money in you know in number 10 and number 15. And we see that effectively with ADCs. There are too many Topo 1-based ADCs, you know, and the targets are not that innovative that the the it is warranted that so many topo one-based ADCs are being developed. So for the moment, we're not able to cure cancer. At least there are a number of cancers that we can reasonably cure, but the vast majority of solid cancers we can't cure. So I think the goal for us as a drug development community in oncology is to extend patient lives in the best possible way, making, you know, maybe not curing the cancer, but being able to live with the cancer, kind of live in peace. A little bit like what happened with the AIDS therapies over time, where you know, people that are positive, HIV positive, still can lead a normal life if they if they follow the appropriate medication these days. That might be a possibility where that's at least that that that would be my dream, so to speak, to get that to patients.

Jack Elands

And I don't think this will be with one generation of ADCs. It will it will it will require a series of various ADCs whereby the cancer, when it's being treated, will develop some form of resistance, and then you will have to come in with another ADC to be able to continue to treat that patient, and then you may want to come in with a third one, etc. And so we actually coined the term a cancer treatment framework to establish this, because if you if you know your cancer, or if the the if the doctor knows the cancer of his patient or her patient, then you could actually develop a treatment algorithm in which you sequence those ADCs and maybe not even wait until resistance is so bad that you you have to but but start to treat a patient with another ADC that basically comes in afterwards. So that idea of a cancer treatment framework is something that we we formulated a while back to see if we could develop our ADCs accordingly. So the first step could be right, now we have a topo one-based ADC like NHER2, patient develop resistance, then we come in with trustees map lurbinectadin. Then thereafter, you know, there is a possibility to come in with yet another ADC with a payload that is clearly differentiated from both NHERT2 and Lurbinectadin. And these payloads, these drugs exist, so we can pick them. Ultimately, I hope that the combination of the targeted delivery of an ADC together with an immuno oncology approach, in which the body is being taught to kill the cancer or being being reinstructed to kill the cancer would would work. This was, of course, the big dream after PD1 PDL1 was discovered.

Jack Elands

But unfortunately, most of the other immune checkpoint inhibitor complexes didn't work out all that well. And so there is a long way to go. But this is obviously if we talk about curing cancer, that obviously is the ideal, the goal that we all should strive for. And maybe that's also possible with an ADC by by only locally affecting the the immunology of the of the cancer and not affecting the immunology in the entire body. If we can achieve that, that would be great. There are a number of companies that have, you know, that are brave enough to go after this. We don't have that scientific knowledge. We don't have the the we don't have the connection ourselves with a groundbreaking academic lab where I think you know the the the the basic idea, the basic the basic science teaching you that something may be possible if you can deliver it very specifically into the cancer. That combination, if we can, if the the field can advance the ADC technology so that another company, another academic lab-based company, could then combine that with an immunocology approach, whether it's an immunogonist or immuno inhibitor, depends on where you want to interact. That might be the ultimate goal, you know, to really get rid of cancer. But I think in the in the short term, I'm still thinking, you know, in tens, at least 10, if not more years, getting to a status whereby during a prolonged period of time a patient can have a reasonable certainty that he can live in peace with his cancer thanks to treatment with acceptable side effects.

Rakesh Dixit

Yeah, some maybe give him more cancer as a chronic disease. Yeah.

Jack Elands

Yeah, yeah. That would be that I think that would be a great first step towards making cancer a livable disease.

Rakesh Dixit

So on the same topic as you were discussing, on the combining the immunosy therapy that have really helped a lot of patients, and then obviously now on a little bit more newer therapies like ADCs in this period in cancer. Combination of these two, definitely we are seeing some really great results, especially with PATSIV and promulgum web combinations and some others. What are your thoughts on developing, like targeting two targets on cancer like biospecifics ADCs with a novel payload? Or, you know, having the same target or biospecific target with two payloads of two different MOAs. Not necessarily the same MOA. I don't like to put two cyotoxic payloads. And will that be something you think is coming in the future? Because I saw there's a lot of momentum at the ACR meeting I saw where I got my hopes up that there is opportunity now. People are looking into dual payloads with different MOAs as well as dual targets that may allow to bring more of these payloads into tumors to kill them. You know, what are your thoughts on bi-specific and dual payloads?

Bispecific And Dual Payload Reality Check

Jack Elands

You know, yeah. I think they're both exciting. We don't do either of them, but that's purely for a reason of focus. You know, we're a small biotech, we need to have focus and our focus is on on novel payloads. That doesn't mean anything for the value of bi-specifics or dual payload approaches. I think bi-specifics can be really interesting in in further enhancing the selectivity for cancer only and and and avoiding targeting healthy tissues. There is still work to be done there. We still we we we we we can improve on that. There are of course also some key questions. You know, if you have a bi-specific, will the relative affinities for both both targets be in the right setting? Which target do you want to engage first with? Which should be the other one? It's it's a delicate all of a sudden you're entering into a field where there are many more questions that you have to investigate. You know, do all cancers that you're looking at express both targets in in the right ratio? Is there heterogeneity? Can cancers differentiate in terms of expression levels? Those need those issues need to be understood, and they will probably only be understood once these bi-specific ADCs are coming to the clinic and see how patients and tumors react to that. But in itself, I think it's a good approach to make more selective ADCs. The dual payloads, I think conceptually, it's beautiful.

Jack Elands

Unfortunately, there's a pragmatic piece to it. You know, CMC, the behavior of those molecules. We're just touching, we're just scratching the surface of those dual payload ADCs. Frankly, when I mentioned this to my CMC guy, he gets an instantaneous headache. It it you make your you make your life very much more difficult um if you do that. It doesn't mean that it cannot be solved. My my basic warning is there are other areas that also need attention. Let's avoid on just going after this because we can. But that's you know, that's easy said. Work has to be done, people have to sort this out. And I think right now people are also doing it because they can. And I'm I'm I agree with you. Just combining two cytotoxic payloads because you can, that doesn't make much sense. I've seen lots of examples where people add topo one and tubulin-based inhibitors. You will come to the clinic and you will be behind other ADCs. So your patient will have probably developed resistance against top of one inhibitors, and you end up basically with a tubulin inhibitor-based ADC. So I think people have to be smart. If you do something, do it because you can help a patient live longer rather than because you can you know technically put it together.

Rakesh Dixit

Well, I think that's that's what I've seen. The problem, yeah, yeah. And then I think very well said, and I think that's where I see the problem with lots of presentation. I saw that at the at the ACR meeting, that the thinking process is what you know people are trying to do is to say, oh, because I have these two payloads and I can combine them, but without thinking about, okay, so you if you're going to combine it to poison with inhibitors like exotal or DXT-like molecule, which by itself causes significant neutropenia. And then you put another payload MME that also causes neutropenia, and not to mention other toxicity like peripheral neuropathy and all that, what are you thinking? You know, are you are you going to see less of it? And and if if you think less of it, why? You know, what are your logic on that? And then, you know, with are you going to see only incremental benefit in efficacy or more toxicity? What the therapeutic index looks like. When you when you talk to the companies who are doing these dual payload technologies, I have seen the lots of companies, they don't have any answer. They are doing it just because they can do it, okay? Or they have they have somebody convince them in their company that dual payloads will make a lot of sense, which we all agree with with that. But there are lots of, you know, to me personally, in selecting dual payloads, you got to do a lot of thinking, you know, why are you combining with what? And then how are you going to deal with not only the issues of therapeutic index, but also the CMC problem, as you mentioned? How are you going to scale up? All that is stuck is still in is not well thought through, at least in my experience.

Jack Elands

So yeah, I would agree. I would agree. And then, you know, I think if you more than one clinician has told me, oncologist has told me that, hey Jack, why don't you just develop an ADC with an interesting novel payload and then let me play around with small molecule drugs to test out combinations in patients that that make sense? Because if you have an ADC and you can synergize with a small molecule treatment, maybe that small molecule is not as toxic as it is when used as a standalone molecule. And I think that makes a lot of sense. We need to another an experiment, it's a very expensive experiment to make a dual payload ADC. And I think we need to very carefully investigate whether that that actually makes sense. And one of the ways to do it is to combine it, you know, to look at small molecule treatments and combine it that way. And if you then have a good combination, yes, you then you may want to go forward and develop that. Oh, absolutely.

Rakesh Dixit

Like combine herbonectidin is small cell lung cancer with an ADC that that also targeting the you know the the lung small cell lung cancer. Can you enhance the benefit without increasing toxicity? I think to me, and if that does, then then it will make a sense to make a dual payload. But my last question is actually it's a question for, of course, you answered some of it, like what the first-time CEO should be doing, you know, and I you you said that having that having that background or experience in marketing and and and business development could be extremely helpful. So so I think those are those are the great points you already described that.

Defining A Lasting Contribution

Rakesh Dixit

So just a last question, and it's a more hypothetical, I have to ask you. So when you when you look back so far in your career, and people say, okay, Jackie Lance, okay, what do you think will be your lasting contribution to the field of the ADC or ADC or any any therapeutic area that you have worked on? But people say, Wow, Jack, you know, this is this is fantastic, what you did, you know.

Jack Elands

To be very honest, at the moment with at Cytherix, I've put a good team together that is able to take care of most things. And what I'm trying to do now with a team of people that is in the company is to help them to advance their careers so that they can actually become successful in biotech after me, so to speak. So I'm I've I've never done this so much as as I've done before. I enjoy it tremendously. We are well financed so that I can, you know, I've been able to put together the team, and it's it's it's a it's an immense pleasure to help other people develop themselves so that they can take on the helm because there is there's only so much that I can do. This is probably gonna be my last company that I'm that I've set up. I won't stop being involved, but the ability to help other people to advance their careers and to guide them to do the right things, that is something that that I'm enjoying right now, and it's an additional goal for me. You know, for for the new company, it's an additional goal that yeah, we we we prepare a next generation of scientists to continue the biotech

Final Thanks And Sign-Off

Jack Elands

world.

Rakesh Dixit

No, I really like that what you said, and and and you know, having worked with you since 2019 in in a in a different capacity, like a more advisor consultant, I have tremendously enjoyed working with you and learned a lot from you. So thank you for this podcast and your guidance and your enthusiasm for the ADC field, and really appreciate your time for this podcast. And and thank you so much.

Jack Elands

Thanks a lot, Rakesh. It was a pleasure, as always.