Panna Sharma, CEO, Lantern Pharma
ACT: While reaching the first-in-human stage is a significant achievement, what specific endpoints or biomarkers will you be looking at in the Phase I trial to assess LP-284’s potential efficacy for non-Hodgkin’s lymphoma (NHL) and other targeted cancers?
Panna Sharma: All the phase I is mostly looking at safety and going for optimal dosing. This is our second phase one clinical trial in this class of drugs that we’ve launched. The first one is LP 184. This one is kind of a sister, drug sister therapy to 184 called LP-284. This one to us is particularly unique, because it doesn’t work in solid tumors like when it for it really works and blood cancers. This is a drug that three years ago, we hadn’t even made, we went from iron from a whiteboard, to a first in human clinical trial with this candidate and about three years at a cost of less than $3 million. And that’s because we used AI, it’s an unheard-of achievement in oncology drug achieve drug development. And the fact that we actually know what to look for mechanistically is also another great achievement. I’ve heard of many drugs that are going into phase one, where the CEOs of the CSOs will tell you point blank, you know, we’re not quite sure how this works, but we know it does something.
Unlike that we actually know what we’re looking for, we think LP 284 was published multiple times, is a highly potent deplete er of B cells. And that’s where a lot of NHLs is arise is CD 19, and CD 20, B cells and T cells. And this drug seems to eat them up B cells in particular, so it’s a potent depleted of B cells. And so that’s one of the key things we’re going to look for, we’re going to look for the depletion of CD 19, and city 20, positive B cells and B cell populations in general. But the other thing that we found with LP 284 is when there’s any kind of DNA damage repair pathway deficiency, like ATM or ATR, it seems to be even more potent. So of course, we’ll be looking for those Hallmark those biomarkers as well, mostly larger scale exploratory biomarkers around DNA damage repair pathways, which are not that common in NHLs. But if you look at the recurrent cases of NHLs, they tend to be enriched. So, these tend to be more aggressive, more rapidly growing. So, we’re going to look at both sets of biomarkers, and that’ll guide our next phase for LP 284. And like I said, this drug went from an idea on a whiteboard to the first human clinical trial in three years at a cost of about $3 million. And so, we’re pretty excited by that.
ACT: Your press release highlights the role of RADR® in identifying LP-284’s potential. How will the insights gained from this Phase I trial be fed back into RADR® to further refine its capabilities for future drug discovery?
PS: We’ll have a lot of data from the pharmacokinetic work. In terms of drug availability, we’ll have a lot of biomarker data around the B cell depletion from, you know, flow cytometry based assays and of course, will have transcriptomic and mutation data probably from the liquid biopsy samples we take. So all that data from that trial is anonymized and fed back into our platform along with outcomes. And we’re going to have a range of outcomes as measured every few weeks. And so those criteria, as measured every few weeks, will be correlated with the biomarkers and will also floor correlate with the evolution of the biomarkers to see, where are we really seeing durable or more complete responses? And where if we find that unique signature even further refined, the patient population, you know, will then go into phase two, looking at a further selected patient population.
ACT: With an estimated 40,000-80,000 potential annual beneficiaries worldwide, how will you go about ensuring global access to LP-284, particularly in regions with limited resources?
PS: One thing I think that’s really unique about this drug in particular non Hodgkins lymphoma is we’re in an era now, where NHLs with recurrent, especially recurrent, are being treated with fairly expensive regimens, Carty therapy by specific antibodies, things that are very hard to pronounce, they don’t have three or four syllables anymore, they have six to nine syllables. And so every syllable, you’re adding another $100,000, I feel like in the pharma world, but you know, those are not affordable drugs. This is a small molecule, we can make this at small molecule level prices. And again, it’s a brand new drug, the drug never been even, you know, had a concept of it, you know, four or five years ago. We think that it can be widely available, easily produced and distributed using the same molecule, small molecule machinery that all the big pharmas have. So we think there’s going to be a lot of interest, especially places where it’s difficult to do Carty, where it’s difficult to whether it’s an autologous or allogeneic. And by specifics are really expensive to produce and distribute, and there’s a lot of cold chain issues, etc. So we think this is a drug that has shown pretty equivalent, if not superior, preclinical data to some of the cutting edge therapies being used. Again, that’s preclinical, but showing preclinical to preclinical if you’ve got pretty equivalent data monotherapy, and actually better data in combination. I think that’s a great starting place.
And our cost of making this drug is a decimal place different than most biologics. I mean, the pharma are addicted to burning cash. And so there’s no there’s no incentive to try to do things cheaper, unless you’re a small company that has no money, every shot that we take has to count. And so, when we designed to eight, four, we looked at the manufacturing process and said, How can we piggyback on the pharmacophores of 184 for its sister molecule? By doing that, it allowed us to really skip through a whole series of some synthesis, and steps and, and do some kind of separation later on down. And we actually, you know, we think we can actually make that more efficient, actually, the next go round.
It’s very exciting because one, we want to make drugs cheaper, that’s kind of our core mission is to make them more precise, and to make them more efficiently. And I think this is a great case study for that. And that’s why we’re particularly excited. And we’re also going to extend to a for the next round in in combination therapy. So, we’ve published on this and one of the Mainstays and non Hodgkins lymphoma as you probably know in your readers or viewers, is rituximab, and we’ve published on 284. Plus, rituximab in combination shows remarkable efficacy, even much better than monotherapy of either drug alone, and we can cut the dose even in half and have even a better window for the for the combination regimen. So, we’re pretty excited by that. And we’re going to do you know, probably that in a phase one beast slash to probably Phase II combination, we’ll probably do a combination of the rituximab and 284 as a safety role and then go to a full combination trial versus 184 alone and see how that does. So again, the avenues because it’s so well molecularly characterized, we’ve got a number of publications. We think it opens us up to actually other diseases outside of cancer. So like I mentioned before, this is a really potent B cell depleted and so B cells play a role in a number of autoimmune conditions as well. And we wouldn’t be the first company looking to partner this asset with some of the big autoimmune players to looking at some of those kinds of diseases.
ACT: The oncology landscape is crowded with novel therapies. How do you see LP-284 uniquely addressing unmet needs compared to existing or emerging treatments for relapsed/refractory lymphomas and solid tumors?
PS: The thing about 284 is, you know, that is novel, it is mechanistically in a class, it’s fairly well accepted and known, it’s, you know, it’s opposed to alkyl later. Now, it’s a selective alkyl later, because it seems to really target cancer cells, or B cells and cancer cells. And not all cells, like most calculators, it also has, you know, several times more potency than most calculators. So, I think the fact that there’s a known mechanism, it seems to prefer cancer cells, I think that makes it unique. And it’s relatively more goal to scale and produce most of the other biologics out there. They’re going after NHL today.
ACT: Can you speak on the anticipated timeline for a next stage and any key milestones to watch for as LP-284’s development progresses?
PS: The key things that we’re going to be looking at this year is obviously in the phase one, to get to our maximum tolerated dose, that’s going to be very important so that we can open up, you know, combination trials, we also expect to have some data toward the end of this year about LP 284 In other autoimmune conditions. So, we’ve actually started a campaign to look at LP 24 and LP two, it is 20 fours mechanism in categories that we historically have not been in but are pretty significant. So that also excites us. And we’ll have some data about that. And I think also we’re beginning a lot of discussions with pharma partners that are historically have larger footprints in non Hodgkins lymphomas, because as I mentioned before, this drug shows remarkable synergy with some of the mainstays in non Hodgkins lymphomas like rituximab and cyclophosphamide, and some of those has great synergy potential.
So, when you think about patients that roll off of that or stop responding to that, effectively, we think that this drug can reenergize and actually be a great option for recurrent events for those patients, which today there aren’t very many of them. That you know, as the data from the trial will tell us everything and will inform us where it’s working best but will also guide us as to what sub indications are genetically defined populations and non Hodgkins lymphomas are even better responders. Right now, we go in with a thesis that mantle cell lymphoma and high grade B cell lymphoma, especially double hit and triple hit are going to be the ones that are most responsive based on all of our preclinical work and based on the in silico analysis that we’ve done. And if we can get a sense of that in the trial. And also, the trial, as you noted, probably is also open to a number of sarcomas.
So certainly, no sarcomas are genetically very, very, hugely heterogeneous. You know, some look more like solid tumors, some look with more like blood cancers, some look like a mishmash of things. And so, there are definitely some sarcomas that we’re beginning to see some good data on in the early phase of this trial. And so, if we see some servos that are uniquely responsive, and as you know, sir Cummins don’t have a lot of options. And so that also could be something that opens up. We haven’t applied for orphan indication in the sarcomas yet, but that’s something that we’ll probably do. And so, you’ll one of the other events we’ll see for 284 is expanding the number of orphan indications we have two already, and we think we’ll probably gather a few others as we develop the drug.
