Okay, let's get underway. Good afternoon, everybody. Welcome to our day two of the Goldman Sachs Healthcare Conference. My name is Chris Shibutani. I'm a member of the research team. We are pleased once again to have Tango Therapeutics join us. Barbara, you and I get to sit down here and, and go through the background of the, of the company, et cetera, but let's remind people a little bit about you. I remember the first time I met, there were all sorts of people across generations in kind of the Boston ecosystem, PhDs. There were a lot of sort of MIT, you know, homies who were sitting there saying, it's like, "Oh, Barbara's incredible.
So you've actually had an interesting journey through academia, through some commercial, you know, familiar large cap pharma stuff, and you're in the CEO role. I think it really helps to get that understanding of who was in the C-suite of focused companies. Tell us a little bit about yourself just to start.
Sure. Well, thanks for asking. Actually, I am, by training, a medical oncologist. I spent the first half of my career in academic medicine. Trained at Dana-Farber, and then on the faculty, first at the University of Michigan and at University of Pennsylvania, where my real focus was on breast cancer, breast cancer genetics, and worked on the BRCA 1 and 2 projects, and that's really what led to my interest in thinking about how to drug tumor suppressor genes, which led to Tango. In the interim, I left Penn in 2005. First, I went to GSK, and then ultimately, in 2009, to Novartis to lead the early development oncology group for David Epstein and then Hervé Hoppenot-
Mm.
- at Novartis.
Mm-hmm.
So I do think, though it was completely unplanned, that it's that what I have done throughout my now pretty long career, 'cause I'm old, is makes me somewhat uniquely suited for this job that I have now.
You are seasoned. We are a fine wine. Tango, how did the company get its name?
Oh, it was named by a Third Rock associate as we were putting together the company. It takes two to tango, so the idea of the target and the genetic abnormality.
Yes, exactly, and then there's sort of kinship with the synthetic lethality.
Mm-hmm.
The whole... There's so many metaphors that reflect this duality aspect of it. It makes sense.
Exactly.
Going back still to ancient history, you guys SPAC'd. You didn't IPO.
Yeah.
You SPAC'd. So post-SPAC, how you feeling about having that heritage, and, you know, what does that make you think about, particularly in terms of, you know, your shareholder base and stuff like that?
Well, we had a very unique SPAC, which is why we did it. So we were in the process of preparing for an IPO. We had done a non-deal roadshow, looking at the whole list of biotech investors that we would like to get into an IPO. And Aaron Davis, who was already on our board-
Mm-hmm
and had led our Series B, had a SPAC, and he said, "What do you think instead about using the SPAC?" And his SPAC, unlike all other SPACs at that time and subsequently, was actually built of the same list of biotech investors that we wanted in an IPO.
Mm.
So that's why we did it, and, you know, I think there's a couple things. One, the shareholder base is, remains largely unchanged. Our redemption rate was somewhere around 2%-
Mm
... which is not the usual number for a SPAC.
Mm-hmm.
You know, I think maybe the bigger issue is that 80% of the company is still held by our top 10 investors, which makes it somewhat illiquid.
Mm-hmm. Okay, yeah, so there's some consequences to sticky money, I suppose, but it's actually very-
We like that. They believe in us?
It is.
But yeah.
Yeah. No, and we've had opportunities to engage, and it's very smart, sticky money, too. So smart, patient, people who, you know, is-
Absolutely.
'Cause this is a journey for a longer period of time because you're taking certain degrees of, you know, innovative, scientific, and clinical risk here. And so when the company came public and the journey that you're at now, we're very much approaching a prime time moment for the company, really over the next 6-18 months-
Mm
... in the clinic. PRMT5 is no longer just a random chant. It actually generates some eyebrow-lifting buzz. There's other folks in the industry here. Tell us about that as a target and maybe frame the opportunity just broadly, epidemiologically, et cetera, before we zero in on what you guys have.
Yeah, thanks, and I would say again, for just a few minutes of ancient history, PRMT5, which is a methyltransferase, therefore an epigenetic target, was initially being developed for... as an epigenetic modulator. You know, no patient selection, just maybe this will work in cancer, sort of a chemotherapy type approach, right?
Mm-hmm.
But the Novartis-Broad collaboration discovered and published back in 2015 that MTAP deletion and PRMT5, actually, it wasn't knockout, it was knockdown, were strongly synthetic lethal. And we picked up on that and developed a PRMT5 inhibitor that actually they speculated in this paper had the mechanism you needed to make a PRMT5 be synthetically lethal with MTAP. That's what we have in the clinic now. That's what Amgen and Mirati, now BMS, have in the clinic, and that's what all the ones coming behind that have.
Mm-hmm. Okay, and I wanna rewind a little bit, 'cause synthetic lethality, such a cool phrase, documented success all the way to the commercial level. PARP inhibitors were essentially the poster child for having made it there.
Absolutely.
More recently, it continues to be a recognized sort of landscape to interrogate, but there are challenges.
Yeah.
There hasn't necessarily been son of PARP, or there hasn't been this cascading, subsequent graduating classes. Talk to me about some of the challenges with synthetic lethality and what's happening to address those?
I think there are two major categories. The first was being able to find the really strong synthetic lethal interactions. Really, until that there was CRISPR-
Uh-huh
to be able to do large genome scale functional genomic screens, it was really hard to do anything but sort of hypothesis-generating work, and the likelihood you're gonna guess right was low.
Mm-hmm.
So I think that's the first thing, and I think the second thing, and Chris Lord at CRUK articulated this maybe the best, which is oncogenic drivers have a very, you know, specific effect, and inhibiting them is often produces pretty dramatic effects, right?
Mm-hmm.
... the synthetic lethal interactions have a wide range of what he calls penetrance, a genetic term, but in any case, we'll say effect size, and may also be more difficult to predict preclinically. So for example, the PARP inhibitors, preclinical data doesn't actually look very good.
Mm.
They're very strong in the clinic. The PRMT5 preclinical data looks strong, and from the data that have been released so far by Amgen and Mirati, I think is strong, but it's in the 30%-ish ORR range, as opposed to the, you know, 70%, 80% you could see with ALK or EGFR.
Mm-hmm.
So yeah, it's a different kind of an animal. It's not a key driver in a cancer. It's often employing some other approach to getting at cancer biology.
Yeah, it almost feels as if the history reflects some sort of teleological journey we found out afterwards by looking-
Mm-hmm
and there's all these pulling of wings from dragonflies and metaphors to stools from, you know, legs of stools, et cetera. So it's kind of interesting to figure out how to get full momentum going forward. You guys and a couple of other companies, we had Lloyd at Repair as well. Everyone sort of taking this avenue, to try and figure out with some of these really challenging targets. So
Yeah
... it's as if the opportunity is there, the journey is one which requires real tenacity with science so.
That's right.
PRMT5, just give us a little bit of a lesson in MTA cooperative?
So it's a complicated story, but the sort of shortest version I can give you is that MTAP deletion results in the accumulation of a molecule in the cell called MTA-
Mm-hmm
- which itself is an inhibitor of PRMT5. And what you need is an inhibitor of PRMT5 that takes advantage of high levels of MTA, so that it preferentially inhibits PRMT5 in cells that have that MTAP deletion and therefore high MTA. So what you want is a PRMT5 inhibitor that binds better to PRMT5 when MTA is present-
Mm-hmm
than when it's not. And that's what we and the other MTA cooperative MT-
Well done
PRMT5 inhibitors have.
Well done. Usually, this involves all sorts of arrows that are curved—and then, you know, sequencing diagrams that we've all been with textbooks too late at night. So but that certainly makes sense. You have two assets here. The genealogy is kind of interesting. I think, 908 and 462, one is more brain penetrant-
Mm-hmm
which is a characteristic sort of that we would expect to see the opportunity to explore maybe in those logical GBM-type opportunities. But talk about these two assets, because I remember the discussion about these. Immediately, we on Wall Street love horse races, and there's gonna be a winner and a loser. You're actually intentionally nurturing a path that is completely sort of interrogating the opportunity set that could make sense for both. Talk about the ultimate end game kind of strategy. Is there a possibility that one will take the lead? And what's interesting to happen is, I think, you know, 462 is kinda like skipped junior high and is almost coming to the same point. So here we are, and a lot of cards are gonna turn for both relatively simultaneously, right?
That's right. So 908 is the first one. It is, as you said, brain penetrant, but it's less potent and selective than 908. A year later, with some additional med chem work, we put 462 into the clinic, not brain penetrant-
Mm-hmm
... but much more potent and much more MTAP selective. And for several well-defined reasons, 462 actually caught up in terms of the clinical study trial to the same point. So based on our earnings release recently, we announced that we were in dose expansion with 908, and then we would be in dose expansion with 462 by the end of the quarter. We updated that this morning to say we're actually now in expansion with 462 as well. So the clinical update for the second half of this year will be both of them simultaneously.
Okay, that's very exciting, especially for Adam.
Yes, it will be.
Keeping him full time, and it's probably good for Daniella as well, your CFO, who has always been very elegant about keeping a straight face as I'm trying to pressure test her on timelines, et cetera. So we're finally at that moment, and thinking about the second half. Let's drill down a little deeper into 908.
Mm-hmm.
The brain penetrant version. Just go through a little bit of the data that you've shared so far. What do we know? We had some proof of concept biopsy data last year. There was a biomarker, SDMA, where you're trying to reduce that. Talk about how that biomarker correlates with possibly a read-through into clinical success.
Well, as you pointed out earlier, all things PRMT5 and synthetic lethal are sort of vaguer than one might like, and it turns out that SDMA is the immediate downstream PD marker for the methyltransferase activity of PRMT5. But it also turns out that the assay is not very sensitive, so you can ablate the signal of the SDMA signal way before you get full inhibition of the enzyme. So it's necessary but not sufficient, and I think that's what everybody has seen at this point. So we have full SDMA suppression with both molecules, but that alone does not guarantee clinical activity.
Acronyms like GBM, glioblastoma multiforme, to be respected, to be feared, to be admired, it takes a certain degree of courage to get there. So maybe you get a bit of a permission slip in terms of what the hurdle rate is, in terms of what defines good data and how many patients we need to see. So help us make sure we're in the correct zip code with both of those. How many patients will we see when we have the data, and what do you think is fair to say this is good data, this program, in this indication, is gonna continue to move forward?
Yeah, so those are a lot of questions at once. I'll start by saying I think GBM is like every other hard tumor-
Mm
... and several of them have already fallen. Get the right drug and enough of it in, and I think that'll be true of GBM also.
Okay.
We will have, I believe, enough data to answer the question in the second half of this year, whether that's gonna be with 908 or that isn't gonna be with 908, but I think it's really all a matter of getting the right drug in. So-
Skillfully done. So I didn't hear an N, and I didn't hear a parameter-
Oh, I can tell you about escalation cohorts.
Okay. Yeah, that-
Those numbers I can tell you.
Leave me with something.
Yeah. So for TNG908, escalation is finished. We actually have approximately 66 patients that have been enrolled on the dose escalation-
Excellent
- portion of the study. The dose ranges are from 25 mg twice a day to 900 mg twice a day, which explains why the study took so long. Remember also that the FDA mandated a 50% increase instead of the usual dose doubling. So to get from 25 mg twice a day to 900 mg twice a day with 50% dose increases takes a while. We are expanding at 600 mg twice a day.
Okay.
At that dose, there are 14 patients from dose escalation that have been enrolled. That includes both the actual dose escalation cohort itself and the backfill.
Okay, perfect.
That's a lot of numbers.
Healthy denominators. That's actually very pragmatic. I think one of the tricky moments are the initial unveiling of clinical data, or people are doing math on very small denominators, and that can become kind of problematic because if you push one patient response in one direction versus the other, the street loves to jump to very dramatic conclusions.
Oh, that's absolutely true.
Jumping dramatically, 462, well, it seems as if the catch-up, the pace of the enrollment there, I always like to, as many do, infer that this has to do with the reflection of some enthusiasm here.
It is, for sure.
Okay.
There were a couple different reasons. One, being a more selective molecule, we were able to start closer to the active dose range-
Okay
- with 462.
Mm-hmm.
We were able to dose double, and it was a year later. So to your point, people were starting to get pretty excited about these molecules, and very importantly, they had gotten used to looking for patients with MTAP deletion.
Mm-hmm.
So TNG462—I would say, going back, TNG908, we struggled with enrollment for sort of the first 6 months. TNG462 opened to a wait list and literally still has one.
Mm-hmm. 908 had a little bit unfairness of the immediate post-COVID, "Oh, my God, nobody's doing early oncology clinical trials"-
Yeah, that was hard, too.
You know, handicapped, clearly, right? By the way, how are we doing just, you know, for the whole ecosystem, early-stage oncology clinical trials? Do we have a better sort of, you know, panoply of people who are staffing these trials and things like that? Have things gotten a little better?
I think so.
It's back to normal pre-COVID or not quite?
I think so on both sides. I can tell you better on the biotech side, it's certainly much easier for us to hire, clinical people, you know-
Mm-hmm
- to Tango.
Okay.
In fact, Adam sent me an email over the weekend, said, "It's raining CMOs." I said, "Well, that's new.
Excellent.
Right?
Okay.
It's a good thing. On the academic side, I also hear from our operations team-
Mm-hmm
that it's gotten better. It's not perfect, but it's definitely gotten considerably better.
Okay. No, that's very helpful. With 462 as well, it seems as if there's potential for a wider therapeutic window.
Yeah.
We're looking at that efficacy profile, safety as well. Comment about what would be the fair way to compare 908 and 462 from that safety and therapeutic window perspective.
I think all of the PRMT5 inhibitors are pretty well tolerated. I will say I think 462 stands out in that regard. One particular measure that I think is fair is that based on the publicly disclosed data from the competitors and what we know about 908 and 462, 462 is the only one that's actually hit true on-target tox with thrombocytopenia and anemia.
Mm.
and very good tolerability profiles up to that point. I think Amgen, Mirati, and 908, the DLTs have all been something else.
Mm-hmm.
So I think that speaks, first of all, to being able to take full advantage of that 45x window-
Mm-hmm
- with very good other tolerability. You know, beyond that, they're all pretty well tolerated.
Mm-hmm. Yeah, I think it's been interesting for Tango as a stock, the performance in the media-
I try not to look at that.
Well, okay, excellent. Yeah, no, I, I always find it worrisome when I walk into a, a biotech company and the CEO's got the ticker running every minute on the stage. It's like, okay, yeah, nose is in the right direction here. But, you know, the, the performance of the stock actually, enjoyed or maybe didn't enjoy, but there was a fair amount of volatility, but uplift as we saw competitive data here. So contextualize for us because we all love to just say blah, blah, blah, caveat or cross-trial comparisons and that. It's real, right?
Mm.
And so give us the Barbara Weber contextualization of, as we look at other data, how we should frame. Bear in mind this when Amgen speaks or bear in mind this when Mirati Bristol speaks.
Yeah. Well, going maybe with the stock price, I'd say we did get a significant bump last summer when Amgen announced that they had activity-
Mm-hmm
... and Mirati showed their data. Because up until that point, people were unconvinced it was gonna work at all. So that was the first big thing. We don't know anything else about the Mirati molecule, except pre-clinically, and I think, you know, pre-clinically, it looks pretty good. Maybe have some bioavailability issues. They have to dose pretty... for activity, and that comes along with the price of a lot of GI intolerability. We've not seen that.
There's always an X, Y, and Z axis, and so, X being sort of response, Y being safety, and Z always crops up durability and duration of response. How are you feeling about what we've seen? It's been pretty limited so far, but what could we see? We think about the, you know, the challenge of what's happening biologically with these tumors, but, you know, what's the right framing of expectations with these patients?
Yeah. I mean, obviously, I have to be careful not to talk about our own data, but I think what we've seen publicly and heard unofficially is that the durability in people who respond to these molecules, including stable disease, is pretty significant.
Can you put some months range-ish around that significant? And again, respectfully, it's this question of, many times when we're thinking about these innovations, we're talking about pretty advanced patients who've been through many lines-
Yeah
of therapy, so significant can mean different things in different settings.
I think at this point I can only talk anecdotally, but I can say, for example, in the Amgen data, there's a pancreatic cancer patient that had a near CR that was on for almost a year.
Okay. Yeah. No, that moves the needle.
Yeah.
Absolutely. These are some very tough situations here. There's very rarely, if ever, a single bullet. Combinations often is the approach, 'cause biology is just a tricky master, and it's often one, two, and then some punches here. Talk to us about how you're thinking about possible combination approaches, and when might we be able to get a peek under the hood of what your playbook is like?
Yeah, and I believe that very strongly. I don't think any solid tumor is ever gonna really cave without critical combinations. You know, Bob Weinberg said this 30 years ago, "We're gonna have to hit at least two or three, and sometimes four nodes in a, in a tumor to really kill that tumor so that it doesn't come back," and I think that that's true. I think what we're looking at is combinat-- orthogonal combinations-
Mm-hmm
... of two different flavors. One is with oncogenic drivers, and our current favorites are those in pancreatic cancer that are relevant to RAS-
Mm-hmm
because almost all pancreatic cancer is RAS-driven. So that means that a KRAS inhibitor, like RevMed, or a G12D inhibitor, like RevMed's and others, could be really interesting in combination with an MTAP. You could also... I mean, a PRMT5 inhibitor. You could also imagine that you get two different things from those. One, with oncogenic driver inhibitors, you get fast responses, but you get sometimes shorter duration responses.
Hmm.
If what we're seeing and hearing about PRMT5 inhibitors, you may get slower responses, but longer duration, the combination of the two could be quite nice. The other combination we're interested in, and it's slightly more speculative, but I think it's real and we really want to do this, is combination with CDK4/6 inhibitors.
Hmm.
Because basically, all MTAP-deleted tumors also have a CDKN2A deletion-
Okay
... which hasn't, in the past, resulted in strong single-agent activity across tumors with CDK4/6 inhibitors, but I think may be something to really consider in combination with a PRMT5 inhibitor. So we're working on those two approaches. I think Amgen's going more down the chemo combination.
Mm-hmm.
We have no idea what BMS is doing, and we're sort of more interested in orthogonal driver combinations.
We think of combinations, and there tends to be a need for some gentleness because of potential for overlapping toxicities. Whenever someone says CDK4/6, I think about resting that bone marrow.
Mm.
So, how should we think about the potential for overlapping tox with PRMT5?
Well, it's a good question, 'cause I just told you with 4/62, we are hitting on target tox.
Right.
It's predominantly thrombocytopenia, a little bit of anemia. I think with those drivers, we're talking about neutropenia. So we could end up with, like... You know, you could say, "Well, it's not overlapping," but you could also say, "We could knock out two or three lines at once at the bone marrow." So just something we'll have to be careful with.
Anytime there's combinations, and it's been fascinating coming from ASCO, thinking about just two targets, but even the modality or the sequencing, whether it's in some form of a bispecific. Somehow, synergy might be too broad a word, but there's some element of benefit that can happen in that instance there.
Yeah.
So when you think about how you're going to tactically approach this, and simply because I think of you guys as having such sophisticated chemistry, you know, talk about your capabilities, and rather than just sort of saying, "Hey, you guys have a CDK4/6, let's jam them together and put them on a date," you're actually gonna have to be thinking much more specifically about how to develop a nuanced profile in order to succeed through that, right?
Yeah. I think, once again, you're dead on, and it... I mean, you have to have, I think, deep pockets and the fortitude to do this, but it's very important. Sequencing, even alternating of regimens could turn out to be really important, and that means that if you look-- I mean, leukemias, lymphomas, testicular cancer, breast cancers, all those regimens that have turned out in the end to be very impactful are just exactly that, to be able to deal with overlapping toxicities. So, you know, let's take it a step at a time and first see what kind of efficacy we get, and then think about how we move those into longer term, you know, combinations that really make a big difference for patients.
Okay. I introduced you to my brilliant associate on my team, Darwin, and he was digging up all sorts of different realms of combinations across the landscape, including from Amgen, a molecule that they're combining with Idea's MAT2A inhibitor. Thoughts?
Yeah. I mean, that's not an orthogonal combination. Those are two inhibitors that hit the same pathway.
Right.
It's a way to try and get better PRMT5 inhibition with the combination than with a single agent. I think we spent a lot of time in the last five years thinking about that, and ultimately came to our conclusion that if you have a really good PRMT5 inhibitor and can fully inhibit the enzyme with a single agent, you won't get any additional-- we won't get any additional benefit out of the combination, and we'll add all the complexity that we were just talking about. I think there's also a, a reason, good reason to think, and some rumors that it did happen, that with the synergistic activity that you get with a PRMT5 and a MAT2A combination-... you also get synergistic toxicity, and you get-- because the MAT2A inhibitors act the same in wild-type cells-
Mm-hmm.
as they do in MTAP-deleted cells. So for us, that's not a big priority. We're more interested in orthogonal pathway inhibition.
Got it. Okay, that's helpful perspective. Let's period, paragraph, turn the page. You have another asset, which is terrific. At this stage of maturity for the company, we always sort of say, "What's-- What else you got for me?" TNG260, coREST inhibitor, STK11 mutant tumors. Tell us a little bit about this molecule and where you're at with it.
Yeah, I think this is another really interesting program, completely different, and it's a very novel idea, the brainchild of our founding CEO, Alan Huang. The idea that you could actually find immuno- sort of immunomodulatory synthetic lethality, if you will. And so in this case, we showed preclinically, and others have shown with retrospective clinical analysis, that STK11 mutations in tumors create an environment that makes those tumors largely resistant to checkpoint inhibition. And that by using a coREST inhibitor that we've developed, TNG260, you reverse those genetic changes and enable those tumors preclinically to become from being strongly PD-1, anti-PD-1 resistant-
Mm-hmm.
to sensitive. That's what that trial is about, and I think it's generated a lot of investigator enthusiasm. I think that trial is going really well, and we should have an update later this year on what's gonna—what the guidance on that program will be.
Yeah, you made reference to sort of the preclinical work that you've done has been in combination with an anti-PD-1 here.
It was. I should say it was designed that way.
Right.
We actually made it to be in combination with no expectation that it would work otherwise.
Got it. If we think about these mutations, there's been other therapies that have been tried before, LSD-1, pan-HDAC inhibitors. Maybe just reflect upon sort of what the journey and the challenges have been there.
I think with the pan-HDAC inhibitors, if you squint, there may be a bit of a signal there, but it's always something that's been impossible to sort out because there's not been complete information on STK11 mutations in those tumors, and in a way, they've been selected against in those studies. So hard to know. Maybe the most interesting thing at the moment is from Jubilant, that have an LSD1 HDAC6 inhibitor, that they've reported one PR in an STK11 mutant patient.
Mm-hmm.
They call it a coREST inhibitor. To us, it doesn't function that way, but, you know, we don't know enough about their molecule to be sure, but the idea is similar-
Okay.
in combination with the PD-1 reversing immune evasion.
I think it's very generous and perfect that you're commenting about... I always find with these novel targets and these early stages, that success begets broader interest. It's like the tide comes in, lifts all boats, and we can talk about sort of the competitive framework ultimately based upon clinical profiles and how that the rubber meets the road. And as we look in that direction, in particular for coREST inhibitors and STK11 mutants, can you give me a little bit of epidemiologic sense for how prevalent and what are we talking about? I think there's actually some very attractive opportunities here in lung, if I'm not mistaken.
Absolutely. About 15% of non-small cell lung are STK11 mutant, so that's a big number. That accounts for about 60%. About two-thirds of STK11 mutations are in lung cancer. The other one-third are in a smattering of breast, cervix, pancreas, and unknown primary, which is usually breast or lung.
Dose escalation ongoing?
Mm-hmm.
What can you share with us about where you're at with that and how that's going, and when we might ultimately be able to get a, get a peek at some data?
Yes. We started with very good and way better than expected PK for that molecule, so I would say the first dose range was pretty close to the active dose range as predicted preclinically. So I think we're already exploring a couple different doses, and we'll have an update on what that trial is gonna look like soon.
Okay. Darwin has unearthed also some work, STK11 and KRAS co-mutations, which he observes, looking at the literature, not infrequent. Could you see this as a potential combination strategy that you would contemplate? Maybe talk about that. That would have potentially involved a G12C inhibitor, et cetera, or a pan-KRAS inhibitor in something that might be histology-agnostic.
Yep.
Another broad avenue to consider. Where does that fit in your mind?
That's right. So about half of STK11 mutant tumors are also RAS mutant, and there's varying data on the effect of the RAS mutant in that setting. So we've got about half RAS mutant, half not RAS mutant, STK11 mutants enrolled. It does lead to interesting speculation about combinations. The issue right now that has to be solved first, though, is with the existing commercially available RAS inhibitors, the G12Cs, combining them with a checkpoint inhibitor can be challenging, right? So this has to be checkpoint coREST RAS. So that's just the one complicating factor.
Let's talk about Tango as a corporate entity and strategy, et cetera, because simply the, you know, the PRMT5 has really just taken the centerpiece here. We don't hear about it as often, but you do have some partnerships-
Mm-hmm.
-Gilead in particular. Talk to us about, you know, how that's worked out over the years, and is there anything that has been part of your experience that shapes your thoughts about, "Hmm, let's do more of this business development type stuff," or you're fine where you're at, you have, you know, you have your own knitting that you're trying to focus on? Talk about Gilead, talk about that approach as a corporate entity.
... Sure. So the Gilead collaboration, we've had for a long time, and it's been a, a very fruitful, very scientifically based collaboration. It's really about target discovery for them in the space of immune evasion. So they periodically select targets, and they license them, and take them to Gilead, and do the work on them. I think we decided early on that-- and that was a pretty big platform deal, but that was enough. We would do one platform deal. It turned out to be with Gilead, and we have not been interested in another one. What we're more focused on now is a development partnership-
Mm-hmm.
and very likely with our PRMT5 program. I mean, you and I have talked about this, that-
Yep.
The PRMT5 development path is a huge one. Pancreas, non-small cell lung, and a whole range of other opportunities. And I think for us, at 150 people based in the US, to be competitive with BMS and Amgen, we're gonna need a global development partner. So I think that's what you'll hopefully see from us next.
Right. And plus, you guys are based in Boston, and the whole Boston-Cambridge ecosystem makes you very well aware of the big shadow presence of some players there. Obviously, a very important source for you to draw some talent as well.
It's also what they're the best at, right?
Mm-hmm.
Big phase III studies and commercialization is their sweet spot.
Right. Exactly. Let's talk some numbers, financials. Cash, I think, at the last reporting, $344 million?
Correct.
Takes your runway, and here's where I always joke with Daniella, the vocabulary is very specific, into, through, what are you saying about-
Into.
Into.
We were saying through 2026.
Okay.
Now we're saying into 2027.
Okay, excellent, and that actually then encompasses certain key sort of proof of concept readouts across now-
Yeah, for our entire disclosed program.
Three programs.
Yeah.
Exactly. I did wanna ask you a little bit, so Alan, who had been part of the initial core team, he sort of budded off, but still sheltered within the same sort of, you know-
Mm-hmm
... the roof and laboratory, et cetera. Plus, he probably didn't want to resign his, like, ping pong tournament champion title.
He still plays in our ping pong tournament. That's true.
Exactly, so, as kind of like a visitor or whatever. But, just curious to know how that's been, because I think there hasn't been distinction in terms of a complete breakoff. Remind us the ties there and what and how he's going?
It is his company.
Right.
A lot of the investors are the same.
Uh-huh.
He is in our space. Alexis and I are on his board, but it's a completely different scientific approach. It is, however, based on this idea of a kind of vulnerability that comes from changes that are different between normal cells and cancer cells, and he hasn't disclosed a lot of that publicly, so I'll leave that to him.
Mm-hmm.
But, the two spaces are completely different-
Okay
-in terms of development.
Yeah. No, but I think it speaks to sort of how generative and productive the core science can be, that it could actually legitimately contemplate establishing a whole other entity and taking it its own specific direction-
Yep
... and the health and the maturity of what you have going on at Tango as well, so.
Also, Alan's brain. It's a very clever idea.
Excellent. Okay, that totally makes sense. I think we've covered a lot here. Looking forward to the second half of this year, I think it'll be very exciting, and we'll see some clinical cards turn.
Yep.
I think this is definitely a name that, especially as people recover from the summer, thinking about catalyst opportunities, TNGX, folks, watch that ticker. Thank you, Barbara. Appreciate it.
Thanks, Chris. Thanks very much.