All right. Good morning, everyone. I'm Stephen Willey, one of the senior biotech analysts here at Stifel, and glad to have with us for MacroGenics, the CEO, Eric Risser. We're just going to have an informal discussion. Eric, not sure if there's any opening comments or kind of brief overview you want to provide before we jump into Q&A.
We've obviously had a great start to the year, had an earnings release last week where we encapsulated some of the key highlights. It's been a good, strong start to the year, building on the momentum that we had generated in 2025. I stepped into the CEO role last August. The team has been very much committed to delivering on our vision and strategy for sharpening the company's focus, maximizing the value of the pipeline, and continuing to strengthen the financial position of the company. Obviously, in the last couple of weeks, we've made a few announcements around the pending sale of our manufacturing operation, additional non-dilutive capital we tapped into from our Sagard partnership, obviously also laying the roadmap for a catalyst-rich year ahead in 2026.
Okay. I definitely want to spend most of the time on the pipeline, but maybe you can just provide a little bit of color around the two transactions you just referenced. The rationale, the economics, and then what this additional balance sheet runway now allows you to execute on going forward.
Yeah. There were 2 transactions announced within a 1 week time span. One was a second monetization deal around the ZYNYZ royalties with Sagard Healthcare Partners, that could bring in somewhere between $60 million-$80 million. $60 million is already in the bank. The residual $20 million is based on 2026 sales-based performance, there's a milestone, which could be variable levels depending on what sales thresholds we achieve. A 1 week later, we announced a transaction with Bora Pharmaceuticals, which is a global CDMO based out of Taiwan. They're looking at this as a potential anchor site to help boost their North American operation, where they already have a presence. That deal is $122.5 million upon close.
Across those two transactions, that could be potentially $200 million-plus of near-term cash coming in, which does extend our runway which we've now provided guidance that we're covered through the end of 2028. If you look at our pro forma cash balance, it is also significant with over $330 million of pro forma cash when you take into account the $154 million that we had as of the end of March, and then the potential proceeds from the Bora deal when it closes, and the Sagard transaction.
Okay. I know you guys have a great history of procuring non-dilutive capital. I know you were behind a lot of those deals when you were head of BD before you stepped into this role, so it's good to see that trend continuing. It looks like the amended ZYNYZ royalty agreement actually improved a little bit in your favor. Was that just a function of having some additional leverage, given how well this product has launched since you did the first agreement last year?
That's right. They've had a nice uptick. They've obviously gotten additional indications approved. Frontline anal cancer now approved in the U.S., in Europe, in Japan. The Q1 number that Incyte reported was about $40 million. That was a 10-fold increase from where they were a year ago, so a nice increase in the ramp. As part of this deal, it is a capped royalty structure, which in the original deal was a 2.0x return for Sagard. With this new deal, we're looking at a 1.7x multiple that could also apply to that early tranche of capital, depending on what the sales ramp is.
Great way to accelerate, obviously, cash, and ultimately positions the company to do what is our bread and butter, which is invest in the pipeline, drive innovation, and being able to take some of these programs to bigger value inflection points, which is really what we're committed to doing going forward.
Okay. Yeah, we cover Incyte. We didn't even know that they were pursuing a frontline lung filing when the manufacturing CRL was announced a couple of months ago. They haven't said anything about it. Have they communicated anything about their regulatory plans with you? Can you say whether or not label expansion into lung would trigger any additional meaningful regulatory milestones?
Yeah. We haven't provided granular detail on milestone triggers going forward, other than highlight that the aggregate value of those milestones is about $540 million. It's a substantial residual royalty milestone. Again, the royalties, which we have disclosed, is 15%-24%. If we do hit those caps, that royalty would fully revert back to MacroGenics. Incyte is leading global commercialization. Again, all the disclosure on where the asset is, I kind of defer to them to provide.
Yep
that update.
Okay. You still have freedom to operate, if I remember correctly, around being able to develop this asset in combination with the wholly owned pipeline. Is that something you could look to leverage as the pipeline matures here going forward?
That is an opportunity for us. It's now an approved PD-1 agent, and obviously, combination therapy is a big part of where oncology development is going. That's an opportunity that we can leverage, having latitude to access that molecule for combination therapy. We are also manufacturing global supply for that program at our facility, although those obligations will convey to Bora once that deal closes, which we're targeting no later than Q3 of this year.
Last week you provided a clinical update in your earnings announcement from the phase II LYNET trial. This is evaluating single agent lorigerlimab. I think it was being dosed at 6 mg per kg.
Correct.
In gynecological malignancies, clear cell and platinum-resistant ovarian. I know the response rate in clear cell seemed pretty encouraging, but I think you did have a little bit of a toxicity issue in terms of the number of patients who were experiencing Grade 3 plus treatment-related AEs, and I think another 10% plus discontinued. Are the treatment-related adverse events you're seeing here, are those in line with that classical immune-mediated ipi/nivo tox that we tend to see, or were some of those more consistent with some of the hematological AEs that you had disclosed when this was put on partial clinical hold a few months ago?
Yeah. We've had a lot of development experience with this molecule, starting with the early monotherapy Dato, and actually had a chance to also explore a range of doses. It was 1, 3, 6, 10 mgs per kg. Ultimately, we settled on 6 as the dose that we took forward in some of the early expansion cohorts. That's also the dose that was studied in the LYNET study. If we go back and look at some of that early Dato as well as some of the more recent PK/PD modeling, we do see, though, that there's complete receptor occupancy for PD-1, even at much lower doses at 1 mg per kg. As we look at some of the other markers like KI67 for T cell activation, ICOS upregulation, which is a marker for CTLA-4 blockade, we also see evidence even at the lower doses, at 1 and 3.
We had seen in the early dose escalation objective responses at that 3 mg dose level, which is what's guiding our thinking to maybe lower the dose and see if we can improve on some of the safety profile. Even in the phase I experience, though, we did not see some of the hallmark toxicities that ipi typically-
Those include colitis, where you see some pretty serious and frequent rates of colitis. In the phase I experience, we only had, and that was over 130 patients that were dosed, only had 1 or 2 Grade 3 colitis events. We have not really seen that in the LYNET study either. In the clear cell cohort, we didn't really see meaningful evidence of colitis at all. There were some of these heme-related toxicities. That was the basis of the clinical hold, where we had 4 Grade 4 events. 1 of them actually ultimately converted to a fatality. Those included thrombocytopenia, some episodes of neutropenia, which potentially could also be a function of the population that we're studying here. These are all platinum-resistant patients. We know that platinum therapy can be pretty harsh and can deplete the bone marrow.
We are seeing some of that heme tox in this study that was included in some of those Grade 3 events that we reported. Again, the hope here is with a lower dose, we may be able to further improve overall safety tolerability, which would position this for both further testing as a monotherapy, but also potentially opens up additional avenues for combination therapy, which is, again, a potential opportunity for us to capitalize on, especially given that we have a broad pipeline of different mechanisms, some of which could be quite complementary.
Okay. I know you discontinued the platinum-resistant ovarian cancer effort for not achieving some undisclosed pre-specified threshold of efficacy. I believe you're now guiding to an update of this clear cell Dato in the first half of next year. Have you established a predetermined response rate or efficacy metric that you need to see that will guide a subsequent no-go decision for this drug?
Yeah. If you look at a predominant standard of care for clear cell in these later-line populations, which is what we're talking about, systemic chemotherapy is single-digit response rates, and that's one of the features of this clear cell gyn cancer population, is that it tends to be very refractory to chemotherapy. Single-digit response rates, very short durability with just a couple of months of PFS. It tends to be more responsive to immunotherapy, which is, again, why we think this could be an opportunity to build a foothold. PROC, by contrast, tends to have a much higher immunosuppressive environment, which is why conventional PD-1 agents as a monotherapy are only single-digit response rates.
I think that is probably one of our lessons learned as you think about, again, the breadth of development experience with this agent is the ability to resuscitate cold tumors where there is this immunosuppressive environment and limited T cell function. That's a tough bar. I think in some of these areas like clear cell or other indications that are more susceptible to immunotherapy, there we can potentially build on the activity that more conventional PD-1s have shown.
Is there appetite to pursue other tumor types? Obviously, CTLA-4 has proven to be efficacious when tolerable in a number of other settings. Is that something you could look to capitalize on if this clear cell Dato goes your way?
We are open to that, and the other piece that we are integrating as part of our go-forward development planning is also more robust translational work to further understand subsets that might be more susceptible to a response and see if we can use that to guide our go-forward development planning.
Okay. Maybe we can shift gears.
I'll just frame out, though, generally, if you think about resource allocation on the portfolio, this is a relatively small nut for us, and it really is. Let's get clarity on the asset and the therapeutic window and the dosing with these 20 additional patients at 3 makes. That would also help position just a good understanding and grounding on the program, which could support also future partnering interactions for the program.
Yeah. Understood. Maybe we can shift gears to the earlier stage pipeline. MGC026, this is a B7-H3 targeting topo one inhibitor ADC. This is the second iteration of a B7-H3 ADC that you've put into the clinic. I think the same antibody scaffold as vobramitamab duocarmazine, this time with a different flavor and clinically validated linker payload. I know we're getting a data update, I believe mid this year, how would you qualitatively characterize the improvement in TI that you've seen with this next gen version?
Yeah. The ADCs, as you said, it's a whole system in terms of the antibody piece, which we do have prior clinical experience with that first generation molecule. There's the linker technology, which we licensed from Synaffix, now part of Lonza. That's the GlycoConnect technology that enables site-specific conjugation. Most of the incumbent players in B7-H3, and we typically highlight four groups that are well-resourced and moving into later stages of development. These include Daiichi Sankyo with Merck, Hansoh, which has a partnership with GSK, MediLink, which has a partnership now with Roche, and then DualityBio, that has a partnership with BioNTech. All these are more random cysteine-based conjugation approaches. You don't have this uniform DAR4 species that we think could potentially provide better therapeutic window. Also, all of these have active Fc domains other than, I believe, DualityBio has a silenced Fc.
By virtue of conjugating to the native glycan, we abrogate any of the Fc gamma receptor binding, which we believe could also support some of these safety challenges around ILD and pneumonitis, and there has been data published suggesting that that is attributed to nonspecific uptake of alveolar macrophages. We also think the payload, which is an exatecan-based cytotoxin that is typically two to fivefold more potent than the deruxtecan, which is the payload that Daiichi has employed in their programs.
It's a very good system. We also have actually shared recently, it's in our corporate deck, some comparative Dato actually highlighting our antibody versus the Daiichi Sankyo antibody. We have a more efficient internalizer, and also when we've done comparative work in some in vivo models, we see superior antitumor activity. Very good construct. Again, how that all translates into a clinical setting, that's obviously a question that we intend to provide some framing as part of that mid-year update. Design a molecule is clearly one opportunity for differentiation, the other is ultimately our development strategy. Which indications are we going to be pursuing? We'll have additional framing around where we'll be guiding folks in terms of lead and priority indications.
One of the hallmark features of this target, and I'd say it's probably a real disruptor in the ADC area over the last couple of years, because it is not a lineage-specific target where you see folate receptor activity, but concentrated in 1 or 2 populations. There's been clinical results showing robust activity across a number of different indications. That includes small cell lung cancer, prostate cancer, osteosarcoma, ovarian cancer, cervical cancer. There's a lot of early anecdotes of activity that have been reported and in some cases already pivotal studies that have been commenced.
Our thinking is this is still the early innings in terms of the B7-H3 ADC becoming an anchor asset that a lot of companies are looking to employ, not just as a monotherapy, but also you're seeing a lot of groups exploring combination therapy with immune checkpoint molecules, including some of these emerging next gen PD-1, VEGF constructs. Both GSK and BioNTech have announced clinical programs in that arena. You've seen groups doing combos with T-cell engagers. Again, I think it's still early innings, and quite frankly, having a solid safety profile. We've highlighted that no ILD at all has been observed in our studies of both the MGC026 and MGC028 molecule could also provide benefits as you think about layering on other orthogonal mechanisms going forward.
Mm-hmm. Yeah. I believe B7-H3 is actually the focal point of a lot of those ADC/TCE combo efforts, which I think is pretty interesting. With respect to this mid-year update, can you just talk about what we should expect to see and learn? Patient numbers, duration of follow-up. Will we have any sense of durability from this update? Should we expect you to be in a position to communicate what the next steps for the program are?
Yeah. What we have, we haven't provided all that granular framing yet. What we have said is the dose escalation was completed late last year, and obviously that Dato will be presented, and some of those patients still remain on treatment. We have initiated multiple expansion cohorts that are tumor-specific and at a selected dose level, and those are progressing, continuing to enroll. We will also, which we have not highlighted to date, is specific guidance in terms of what are those lead indications, which will also provide a sense of what a future development strategy would be. I think for each of these, there's still opportunity to compete and position ourselves as a preferred regimen.
Okay. How do those indications that you may or may not choose for future expansion efforts, how are those informed by your perspective on the ability to sequence these different flavors of TOP1 derivatives in patients? I guess, are you concerned, or do you think about this concept of there being kind of a shared resistance of, a shared mechanism of resistance that may preclude you from giving, say, a lung cancer patient MGC026 if they've already received something like Dato or an integrin beta-6 targeting ADC that has the same flavor payload on it? How does that color your indication selection process?
That is definitely a challenge in terms of repeat administration of TOP1-based ADCs, and there's been Dato highlighted that those resistance mechanisms are real. Now, some of these targets do restrict based on certain levels of expression levels. Obviously, mirvetuximab, for instance, which is a non-TOP1 payload, but they do restrict to patients that have moderate to high levels of folate receptor. If you're not in that overlapping segment, that could still be an opportunity to compete. That is guiding our thinking, that we ultimately would like to position ourselves not as a follow-on therapy behind another TOP1. That's why we're not going to be pursuing things like small cell lung cancer, which are already now well into phase III development, already moving into frontline therapy in combinations with immune checkpoints. That will be a lower priority for us going forward.
Okay. MGC028 is another clinical stage ADC. This targets ADAM9, same linker payload as 026. I know you're looking at this in kind of a pre-specified set of solid tumors that I believe have been selected on the basis of target expression. Can you just kind of remind us of what this landscape looks like from a competitive perspective right now? I think folks really maybe aren't as informed with respect to this target as they are with B7-H3. Maybe you can just give us a little bit of a preview with respect to what we should expect from this update in the second half of the year.
Yeah. This program, we start our phase I about a year after 026. It is a first-in-class program where we're kind of leading the pack. Although, in the arena of ADCs, there's just a lot of competitive intensity. Many of these molecules are actually coming out of China. There are, in the last year or so, 2 other groups that declared that they'll be moving phase I assets forward. Also, TOP1-based ADCs targeting ADAM9. That includes DualityBio, which started their phase I program, and I think highlighted they had 7 or so patients that have been enrolled as of the end of last year. BeOne has also more recently highlighted that they'll be starting a phase I program of their own. We're still completing the dose escalation for this molecule. We highlighted a planned clinical update later this year.
In terms of indications, this does include a broad swath of tumor types. Some of them are GI-associated cancers like gastric, colorectal, pancreatic. Potentially lung is another indication. Actually, our first-gen molecule, which was a maytansinoid directed against ADAM9, there we did see some early evidence of anti-tumor activity in the lung. It was, again, a different class of payload. Maytansinoids, which are cell cycle-dependent cytotoxins, tend to work less well in some of these GI cancers that are a little bit more resistant. Again, different payload, and I do think it could open up opportunities in a broader range of indications.
Okay. You also have a collaboration in place with Gilead. There's a CD123 targeting bispecific that's the most advanced out of that collaboration. That's been in the clinic now. I think it's been in dose escalation for at least a couple of years now. What can you say about how that program is progressing and if there's a chance we get any preliminary Dato over the course of the next 6 to 12 months, and then how Gilead's option to license this program gets triggered?
Yeah. The early partnership was put in place in late 2022. It is on CD123 by CD3 bispecific, targeting primarily AML, MDS, other CD123 positive hematologic malignancies. There was a MABEL dosing schema, which did require much more metered dose escalation, and that's been kind of an ongoing effort. It is an active program. Actually, about a year after we initiated this partnership with Gilead, they came back and want to add a second molecule into the mix, which is also a variant of a T cell engager approach. Most recently, in November of last year, they added a third molecule in the mix. We do have three active programs, one in the clinic, two preclinical. Most of the disclosure is really gated by Gilead at this point.
specific program updates. They do have, it's an option that's embedded into this agreement, where we're actually executing the phase I study. At these predefined decision points, they can opt in and take on development responsibility, and that would also have a milestone embedded in that. Across the 3 assets, the original deal had about $1.7 billion of biobucks. We've already collected about $100 million or so across those 3 molecules. Again, there's still a lot of potential upside with those assets.
Okay. Maybe last question. Let's fast forward five years. What do you hope or want the MacroGenics pipeline to look like? Do you think that within the pipeline, there will be a modality that is over-represented, whether that's ADCs, TCEs, or just multi-specifics?
What we did also highlight on our last earnings release is our research team has continued to be a very productive group with about one IND a year coming through. The bias is increasingly towards first-in-class approaches. Our next molecule, which is MGC030, that's another TOP1 agent, although it's a first-in-class potential program, so that we're looking to move into the clinic later this year. We do have plans for at least two additional molecules where we'll have early product candidates selected, and those are largely in the arena of next generation T cell engagers, moving beyond traditional CD3 constructs to target populations where you potentially have even better safety and tolerability profile, less cytokine release, which you see predominant a lot of the CD3-based targeting approaches.
Potentially also ways to extend the T cell activation and avoiding T cell exhaustion that you also see with some of the other constructs. That's one clear area of focus, and we've been obviously in the T cell engager arena for quite some time.
Yeah
lessons learned, and we're trying to apply those lessons to create what could be really compelling product opportunities. Similarly, on the ADC arena, given some of the things that we just talked about in terms of resistant patterns, starting to think about what's next beyond conventional TOP1 ADCs, and that's an area that we're also investing in with potential lead molecules being generated over this next year or so. So definitely a lot of focus on innovation within the early portfolio, and then obviously on the later stage portfolio with these clinical programs, we're now well-positioned, and obviously our capital base is significantly expanded, so we have the latitude to drive these two really important value inflection points.
All right. Well, that's all we have for time, Eric. Really appreciate it. Congrats on all the progress you've made since being in the seed, thanks everyone for listening.
Great. Thank you so much. Take care.