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spk03: Good afternoon. We will begin the Macrogenics 2023 Second Quarter Corporate Progress and Financial Results Conference Call in just a moment. All participants are in listening mode at the moment, and we will conduct a question and answer session at the conclusion of the call. At this point, I will turn the call over to Jim Carroll, Senior Vice President, Chief Financial Officer of Macrogenics.
spk08: Thank you, Operator.
spk07: Good afternoon and welcome to Macrogenics' conference call to discuss our second quarter 2023 financial and operational results. For anyone who has not had the chance to review these results, we should have press released this afternoon outlining today's announcements, which is available under the Investors tab on our website at macrogenics.com. You may also listen to this conference call via webcast on our website, where it will be archived for 30 days beginning approximately two hours after the call is completed. I would like to alert listeners that today's discussion will include statements about the company's future expectations, plans, and prospects that constitute forward-looking statements for purposes of the safe harbor provision under the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in the risk factors section of our annual, quarterly, and current reports filed with the SEC. In addition, any forward-looking statements represent our views only as of today and should not be relied upon as representing our views as of any subsequent date. While we may elect to update these forward-looking statements at some point in the future, we specifically disclaim any obligation to do so, even if our views change, except to the extent required by applicable law. And now I'd like to turn the call over to Dr. Scott Koenig, President and Chief Executive Officer of Macrogenics.
spk05: Thank you, Jim. I'd like to welcome everyone participating via conference call and webcast today. This afternoon, I will provide key updates on our clinical programs. But before I do so, let me first turn the call back to Jim, who will review our financial results.
spk07: Thank you, Scott. This afternoon, MacroGems reported financial results for the quarter ended June 30, 2023, which highlight our financial position. As described in our release this afternoon, MacroGems total revenue was $13.1 million, for the quarter ended June 30, 2023, compared to total revenue of $26 million for the quarter ended June 30, 2022. Revenue for the quarter ended June 30, 2023 included recognition of $1.6 million in contract manufacturing revenue and marginza net sales of $5.1 million, compared to net sales of $4.7 million for the quarter ended June 30, 2022. Our research and development expenses were $43.2 million for the quarter ended June 30, 2023, compared to $51.7 million for the quarter ended June 30, 2022. The decrease was primarily due to decreased costs related to discontinued studies, partially offset by increased expenses related to preclinical antibody drug conjugate, or ADC, molecules, and increased clinical expenses related to lorajirulamab and Vorbiduo, Our selling general and administrative expenses were $13.7 million for each of the quarters added June 30, 2023 and 2022. You'll notice approximately $100 million as a component of other income on our income statement. Let me take a moment to explain. Under GAAP guidelines and pursuant to FASB's ASC 470 in March 2023, we recorded the $100 million proceeds received from the sale of our royalty interest on global net sales of T-Zield to DRI Healthcare Acquisitions LP, or DRI, as a, quote, liability related to future royalties, unquote. This liability was to be amortized over the term of the arrangement using the effective interest rate method. Sanofi subsequently acquired both Prevention Bio and the T-Zield royalty interest and milestone obligations from DRI in April 27, 2023, obviating the need for macrogenic involvement in the transfer of royalty payments to DRI. This resulted in a change to the arrangement, which was evaluated as a modification out of the provisions of ASC 470. Accordingly, we recognized approximately $100 million as a component of other income on our financial statements for the quarter ended June 30, 2023. Our net income was $57.5 million for the quarter ended June 30, 2023, compared to a net loss of $41.3 million for the quarter ended June 30, 2022. Our cash, cash equivalents and marketable securities balance as of June 30, 2023 was $240.3 million compared to $154.3 million as of December 31, 2022. Our cash balance as of June 30, 2023 did not include a $50 million milestone payment from Sanofi subsequently earned. Payment of this milestone was triggered pursuant to Sanofi's July 28 announcement that the PROTECT placebo-controlled study investigating T-Zield or tiplizumab in patients with newly diagnosed stage 3 type 1 diabetes met its primary endpoint, having demonstrated preservation of beta cell function. This milestone was part of the March 2023 agreement originally between Macrogenics and DRI. the royalty interest and milestone payment obligations of which were sold by DRI to a subsidiary of Sanofi in April 2023. And finally, in terms of our cash runway, we anticipate that our cash, cash equivalents, and marketable securities balance of $240.3 million as of June 30, 2023, the $50 million milestone subsequently earned in addition to projected and anticipated future payments from partners and product revenues should extend our cash runway into 2026. Our anticipated funding requirements reflect expected expenditures related to the Phase II Tamarack clinical trial, the Phase II study of lorajirulamab in metastatic castration-resistant prostate cancer, as well as our other clinical and preclinical studies currently ongoing. And now, I'll turn the call back to Scott.
spk05: Thank you, Jim. We continue to believe our proprietary pipeline of product candidates has great promise. and I will walk you through each of our key programs momentarily, as well as tell you about our plans for upcoming clinical programs. But before I do that, I'll quickly remind you that over the past year, through our business development efforts, as well as milestone achievement, we have generated $320 million of non-dilutive capital. Volverminimab Duocarmazine, or Volver Duo, is our ADC designed to deliver DNA-alkylating durcomycin cytotoxic payload to tumors expressing B7H3. B7H3 is a member of the B7 family of molecules involved in immune regulation. VOBRDUO is designed to take advantage of this antigen's broad expression across multiple solid tumor types. We began enrolling the Tamarack Phase II study of VOBRDUO in patients with metastatic castration-resistant prostate cancer under a modified study protocol during the second quarter. You may recall that we made this modification to address the changing treatment landscape for patients with MCRPC, and enrollment has been proceeding nicely. We hope to enroll a majority of the 100 patients across the two experimental arms of two mgs per kg or 2.7 mgs per kg every four weeks in 2023 and provide a clinical update in 2024. Next, I'll update you on lorigerolimab, our bispecific tetravalin PD-1 by CTLA-4 DAR molecule. We designed lorigerolimab to have preferential blockade on dual PD-1 CTLA-4 expressing cells, such as tumor infiltrating lymphocytes or TILs, which are most abundant in the tumor microenvironment. You may recall that we presented encouraging preliminary clinical results from a single-arm dose expansion study of lorajerolimab in patients with advanced solid tumors in a poster session at the ASCO General Urinary Cancer Symposium in February 2023. Based on the strength of the MCRPC data presented, we plan to commence enrollment of a randomized phase two study of lorajerolimab in combination with docetaxel versus docetaxel alone, and second-line chemotherapy-naive MCRPC patients in the coming weeks. A total of 150 patients are planned to be treated in the two-to-one randomized study. The current study design includes a primary study endpoint of radiographic progression-free survival. In addition, we continue to enroll patients in the phase one dose escalation study of VOBRDUO in combination with loridrolumab in patients with advanced solid tumors, including renal cell carcinoma, pancreatic cancer, ovarian cancer, hepatocellular carcinoma, MCRPC, and melanoma. We anticipate commencing the dose expansion portion of the study by year end, 2023. Next up, MGD-024 is our next generation bispecific CD123 by CD3-DAR molecule that incorporates the CD3 component designed to minimize cytokine release syndrome while maintaining antitumor cytolytic activity and permitting intermittent dosing through a longer half-life. Our phase one dose escalation study of MGD-024 is ongoing in patients with CD123-positive relapsed or refractory hematologic malignancies, including acute myeloid leukemia and myelodysplastic syndrome. Recall that Gilead has the option to license MGDL24 at predefined decision points during the phase one study. Finally, inoblutuzumab is an FC-optimized monoclonal antibody that targets B7H3. Based on the recently published results from a Phase II investigative-sponsored study of in men with prostate cancer, macrogenics and collaborators at multiple academic institutions plan to initiate an investigative-sponsored randomized translationally intense neoadjuvant prostate cancer study in high-risk population by early 2024. And now I'd like to give you some perspective on where Macrogenics intends to advance. I'll remind you that over our history, we have maintained our focus in developing innovative antibody-based therapeutics, having had a role in the development of three products now approved by the US FDA, Margenza, T-Zield, and Zinus. More recently, as an extension of this emphasis, we've accelerated our ADC efforts. This has been possible through the following. First, our technology-enabling partnerships, most notably our two collaborations with Synaphix, which has recently been purchased by Lanza. We have reviewed multiple linker payload technologies and are pursuing Synaphix's approach, which utilizes various linker toxins conjugated to a site-specific glycan within the FC domain of antibodies. This affords us the ability to exploit different cytotoxic mechanisms, including topoisomerase inhibition, microtubule inhibition, and DNA damage in up to seven ADC molecules, incorporating Synaphex's technology. The second element we believe allows us to extend our reach into ADCs is leveraging our 20 plus year history of pursuing first in class target discovery in addition to our antibody engineering expertise. And finally, the third element is our proven ability to develop product candidates through FDA approval, coupled with our commercial scale manufacturing and external supply chain management capability. We are very excited about where this could take us in developing ADC to treat . As previously indicated, we intend to submit an investigational new drug or IMD application to the US FDA by the end of this year for the first of potentially multiple new ADC molecules which incorporate a topoisomerase inhibitor payload. To conclude, we believe we have the technical development and clinical expertise and even the necessary financial resources to support execution on our plan of developing and delivering life-changing medicines to cancer patients in 2023 and beyond. We would now be happy to open the call for questions. Operator?
spk03: Thank you. If you would like to ask a question, please press star 11. If your question has been answered and you'd like to remove yourself from the queue, please press star 11 again. Our first question comes from Jonathan Chang with Leroy & Partners. Your line is open.
spk06: Hi, guys. Thanks for taking my questions. First question, can you give us a sense of how enrollment in the Phase II TAMRAC study has progressed? Just trying to get a sense of when in 2024 we might see data.
spk05: Thank you, Jonathan. I'm very encouraged by the rapidity of enrollment at this point now as And many of the sites have incorporated the amendments to the protocol. We still have additional site initiation visits to complete on additional sites. But based on what we've been seeing in this group of sites, I stick with what I have said that the majority of patients should be enrolled in the study this year, and we should complete it in the first part of 2024.
spk06: Got it. Thank you. And second question, what do you need to see from either of the Phase II prostate cancer studies to support advancing these programs into the next stage of development?
spk05: So with regard to Tamarac, as you know, we had seen very encouraging data with regard to late-stage MCRPC patients, with regard to PSA50 reductions, as well as objective responses. The goal of this study, in fact, is to achieve responses in terms of efficacy that were similar to that observed at the doses that we had treated before, as you recall, 3 mg per kg on a Q3 weekly basis, but which most of those patients had dose reductions during those course. What is more important at this point is to see some improvement in the side effect profile. In particular, the most disconcerting side effect was hand-foot syndrome in these patients who developed grade 2 with pain. So we would like to see a reduction, obviously, in that grade and obviously the incidence as well. With regard to the efficacy parameters, again, just to refresh everybody's memory, we saw approximately half those patients had PSA 50 reductions. So, of course, we would like to see in the order of around 40% to 60%. or even better, obviously, if that is achievable in that population with concomitant tumor control and continued treatment. With regard to the lorajerolimab study, in terms of outcomes, obviously, we were looking for an acceptable safety profile. In terms of efficacy, If you look at the historical data in terms of control groups, which we obviously include here of patients treating with docetaxel, historical data says an RPFS of eight months is what you would like to exceed. So we'll have to see if we're able to achieve that by certainly several months.
spk06: Got it. Thanks for taking the questions.
spk03: Thank you. Our next question comes from Peter Lawson with Barclays. Your line is open.
spk10: Thanks, Scott. I guess initially just as a follow-up to Jonathan's question, the data that we could see for your B7 and H3, for the Phase 3, sorry, the Phase 2 data, can we see that in the second half of 24 and for the Phase 1 combination data? Is that something like a first half 24 data set scope?
spk05: So, Peter, as things go now, as I said to Jonathan, the encouragement about where we are enrolling, if this continues at this pace, I think the second half 24 presentation of data is certainly possible for the Tamarack study. So obviously we'll have to monitor that the rest of the year in terms of enrollment. I should also point out that this is an open study, so we will take interim looks at that data along the way and may be able to come to some conclusions earlier before we even have the full body of data from that study. So, again, I would be consistent with targeting the second half of the year, you know, at this point. With regard to the combination study, as we pointed out, we're sort of trying to fine tune the combination of VOBRA with lorajerolabab right now individually in combination. Once we settle on what that dose to use, the doses to use moving forward in combination in expansion studies, we expect that to occur by the end of the year. So again, Could it be the first half of the year? Possible. But right now, let me bring you up to date once we have picked those doses and started those expansions. I'll be able to give you a little bit more definition when that will happen.
spk10: Richard, thank you. And then on ADAM9, I noticed an update this year. What kind of update will that be? data, is it kind of a go, no-go decision, and will the data involve the lung cancer data set?
spk05: You know, so as you know, and we discussed this before, Immunogen is conducting clinical studies. They're following through on the patients with lung cancer to identify an appropriate adult, making decisions about go forward. We have not discussed with them the specifics about what would be discussed and presented, we should be doing that soon. So, again, updates later this year, the nature of what will be contained, I don't have an answer to you at this time.
spk10: Great. Okay. Thanks so much, Scott.
spk03: Thank you. Our next question comes from Charles Liu with Guggenheim. Your line is open.
spk00: Hi, guys. This is Rosie on patrol, too. Thanks for taking our questions. So first question is, with regard to the changing landscape in MSBUC CRPC, how are you changing or setting expectations with regards to the valid positioning of Overduo and Laura Gilliam next to something like Flipicto?
spk05: So if I understand your question, how are we anticipating the use of these drugs in face of where Plavicto is at this point and in the future. Is that correct? Yes. Okay. So, you know, clearly, Plavicto is, has changed the landscape for treatment. It is being used currently right now in major medical centers that have PET scanning capabilities for PSMA. There has been, as you know, some limitation in its distribution in terms of supply, which is being addressed by Novartis. So there will be increased use with time. I think at this point, we'll, you know, we have to wait to see the data on the results of Plavicta in earlier lines of therapy. So right now, it's more in a later line of therapy. When we have completed our study results, we will evaluate where the appropriate line of therapy will be and which populations. But right now, it's just too early. Also mechanistically, we're talking about completely different mechanisms. and also the toxicity profiles are quite different. And so I think that this is an opportunity where different mechanisms of action give a greater number of choices for treating physicians and their patients. So I think it's a good story for patients that new modalities will be available very soon.
spk00: Thank you. And if I can ask a second one real quick. This one's regarding the Bova Duo combo. Are there specific histologies that you potentially want to focus on for the dose expansion?
spk05: Well, as we've pointed out in today's call and previously, we are looking at six different solid tumor types right now. We have not selected which ones to do yet for the expansion. Certainly, prostate cancer will be one of them, but which additional others we will select, we have yet to make that decision. Then we'll, again, in the near term, we'll be able to provide that information.
spk03: Thank you. Our next question comes from Edser Durout with BMO Capital Markets. Your line is open.
spk11: Great. Thanks for taking the question. First one, just wondered if you plan to disclose any of the data from the dose escalation of VOBRA Duo plus loridrolumab prior to moving into expansion studies. And then secondly, if you maybe could comment on the progress of any of the kind of other tumor types, LORI sort of monotherapy, maybe any progress there with other tumor types. when we could get an update there or any other tumor types that you would look to explore with Flora, either monotherapy or combinations. Thank you.
spk05: Yeah. So, Edson, we'll have to, again, as you know, as I've said just earlier today, you know, we're honing in on the specific doses for the individual components of the VOBR-DUO combo. Ultimately, it'll be determined of how many, patients we have available that time to assess. My inclination right now is to start and move forward in expansions in particular types, which I alluded to before, prostate and probably one or two others. And probably at that time, Once we have that data, we would be in, I think, a better position to present the total data. But again, this is subject to further discussions later this year. With regard to other tumor types for Laurie, besides the data we presented at ASCO-GU, as you know, we have previously said that we've had objective responses in three other cohorts that we were testing, including MS-stable colorectal cancer, melanoma, and lung cancer. What I've also indicated on previous calls is that for us to move forward into a more wholesome phase two study, I'd like to see some additional patients being treated as monotherapy to better determine the activity in particular tumors. I pointed out, for example, in the lung cancer cohort that we had, we lost a lot of that data because of patients that were treated in Ukraine. For the case of the MS stable colorectal cancer patients, I pointed out we had very few patients without liver metastasis, which has been an area being pursued by others. So I'd like to see additional patients being treated as monotherapy before making the decisions going forward. The melanoma data we're very encouraged by. As you know, historically, we have noted that we've had very significant responses and with VOBR duo and melanoma as well. And that is one of the tumor types we're potentially enrolling in the combination study going forward, so.
spk11: Great. Thank you.
spk03: Thank you. Our next question comes from Kaveri Pullman with BTIG. Your line is open. Yeah, good evening.
spk14: Thank you. Thanks for the updates and for taking my questions. Sorry if I missed this, but for lorajolamab and docetaxel combination study, it's a randomized trial for 150 patients. Can you give us a sense on how long it will take to enroll the study and to get RPFS? Also, do you think that you can just expand it to a free trial if the interim data looks good? Just want to know how you're thinking about it.
spk05: Yes, Kaveri, thank you very much. So we're very close to enrolling the first patients. We've initiated sites. Patients are being screened now. So we're really on target for what we have said with regard to the startup of this trial. Right now, until you start enrolling, you won't know the rate of enrollment. But right now, the anticipation is It will take us through this year and through a good part of 24. And so at this point, it would be just too early to predict when we'd be able to do the readout at the study. You know, most likely in early 25, but that's all conjecture at this point.
spk14: Got it. That's very helpful. And then for MGD-024, can you tell us how is the enrollment going? Any feedback you have received from the physicians so far? And can you accelerate dosing based on your previous clinical experience with Flutafizumab here?
spk05: So, as you know, irrespective of what the product is, any CD3-based bispecific molecule when interacting with the regulatory agencies, There is a lot of prudence in terms of the dose escalation speed in which these things can be conducted, despite the fact that we had very significant data showing dramatic reductions in cytokine production in primate model systems and anticipate that we could move this faster. But having said that, we are following what was discussed with the FDA. We are right in the middle of a dose escalation. The study is going well. And that's all I can say at this point. My sense is that once the dose has been picked from that dose escalation and we go into a more phase two-like study, there may be greater opportunities to accelerate the development. But again, That will be either with Gilead if they opt into the program after the phase one or during phase one, or by ourselves if it warrants it. So it's still too early to tell.
spk14: Makes sense. Thank you.
spk03: Thank you. Our next question comes from Yagal Nakamovitz with Citigroup. Your line is open.
spk12: Hi, Scott. Thanks for taking the question. On the Tamarack study in metastatic CRPC and then the phase 1, 2 dose escalation with the combo, and I think you mentioned CRPC there as well, and you want to do an expansion. Can you just comment, are those patients, those prostate patients, relatively similar in their degree of pretreatment? You mentioned advanced solid tumors for CRPC, so it wasn't clear if it was
spk05: similar or if the ones in the phase one two were more significantly pre-treated versus versus Tamarack thanks so there's some slight differences in ineligibility we have a little bit wider in Tamarack but the majority of the patients will be quite similar so I'm you know we obviously wanted to compare apples to apples with the modification of dose We obviously wanted to get this enrolled quickly, so there was some minor changes, but I would say they'll be very easily comparable to the previous data. And the same story with the combo for whatever prostate patients come in, very late stage patients as well, typically have advanced on antigen-receptive targeting agents on a taxane, and often
spk12: experimental agents as well so we think the data set will be we will be able to compare each one so the reason I ask is because I mean if you do the prostate expansion phase one two with the Vobra and the Liragelamab and that looks really good I'm just curious how you're thinking about a pivotal study and how you would register the product because I whether you'd, you'd, you'd want to register with, um, with the monotherapy, with, uh, Robert duo, or there's the load to lower Jill and that rubber duo looks really good in prostate. If that would be the way to go forward, um, to, to, to take the drug to mark the combo to market. That's more of a strategic, strategic question, but just curious how you're thinking about that.
spk05: Yeah. I mean, you know, so obviously we, this is constant discussion. Obviously we, you know, we, with the data on the Lord Gerald map mono story, being so encouraging, we decided to move a little bit up the line with now going into chemo-naive patients, but with antigen receptor-experienced patients. So that, you know, right now, there is no other checkpoint that is vying for that population. So this is a great opportunity that we can demonstrate in that line of therapy success. With regard to the VOBR story, either as monotherapy or potentially combination with Laurie, that's a nice problem to have if both look very successful, both the results from Tamarack and then the combo. So we'll address that as the data comes out next year.
spk03: Thank you. Our next question comes from Steven Willie with Stifel. Your line is open.
spk09: Yeah, good afternoon. Thanks for taking the questions. I guess now that you've removed the control arm from Tamarack, I'm guessing there's going to be more of an emphasis on response rate versus, I guess, any kind of event-driven efficacy data. So I guess I'm just curious, based upon the eligibility criteria of Tamarack, you know, what percentage of patients you're expecting to actually have soft tissue disease that is resist-available?
spk05: Oh, with that, from that parameter, I think our experience in many of the trials to date has at least capped those patients, and I would not be surprised, given this is an international study, based on actually the results from the LORI trial that we presented, almost all, the majority of those patients had visceral involvement. It was not only bony involvement. So I'm not, at this point, I am not concerned that we will be seeing a tissue-limited population. I think there'll be enough data to that. And then clearly we'll monitor that going forward, and we certainly can add more patients if necessary, but I don't think that's going to be a problem.
spk09: Okay. And I guess just a question on Vover Duo. So you've pressed the pause button here on single-agent dose expansion in other tumor types. I think that's despite some of the early signs of efficacy that you talked about earlier. Are you thinking of reinitiating any of those development efforts, again, once you get confirmation on dosing and scheduling from Tamarack? Or does this next-gen ADC effort now kind of get prioritized in front of Oberdu?
spk05: Yeah, I mean, my answer to you is we certainly are interested, given the broad expression of B7H3, of course, you know, a large number of solid tumors and our experience with them. that additional tumor types will be pursued. Clearly, we would like to see with Bober Duo that improvement in safety, which I discussed earlier. And I mean, I can guess that at this point, or we could forge ahead and just move there. But I think it's more prudent given, as I said earlier today, Enrollment is going well, and we'll have the answer soon to initiate other at that point. We feel very strongly that we are building a great opportunity and franchise within prostate cancer, you know, with the Laurie, with Vobra, potential combination. And then as we said today, the plans to start with academic collaborators, a neoadjuvant study with inoblituzumab in prostate cancer. So we're trying to really cover the entire landscape for treatment of patients with prostate, but that does not interfere with our enthusiasm for pursuing this in other tumors as well.
spk09: All right. Thanks for taking the questions.
spk03: Thank you. Our next question comes from John Miller with Evercore ISI. Your line is open.
spk13: Hi, guys. Yeah, thanks for taking the question. I would look to ask more about the financials and the runway guidance. So, obviously, you mentioned that covers Tamarack and Lloyd Base, too, and ongoing jobs. How much does that cover of a new ADC? How much does that cover? for trials that aren't currently running or anticipate to start? And does that count any new indications either for Vover Duo or for LORI and expansion?
spk05: Yeah, thanks, John. Very good question. Obviously, with today's announcement, we're very excited about getting that additional $50 million milestone from achieving it through the results of the protect study and so obviously just again to put in context as we said earlier with the 320 million dollars in the past year of non-pollutive capital the likelihood of additional milestones goes up because of the hitting the primary endpoint of course it's dependent on the opportunity to get T-Zield approved in the new indication as well as different regions for the original indication that has been already approved in the U.S. FDA, but that increases likelihood there, which means potential increased opportunities for more milestones as well as royalties. I should also point out that Insight announced last week that they completed an enrollment in the two registration studies for the anti-PD-1 sinus in lung cancer and anal cancer. So again, with those readouts as results accrue, if those are successful, what we have on the table are a potential 320 million dollars of regulatory clinical milestones another 330 and commercial so 600 million there and we still have the potential for another 380 million dollars from Santa Fe so that's over a billion dollars of potential milestones from two approved products so getting back to the the essence of your question Just with this additional 50 and the studies ongoing, that does include the new anybody drug conjugate that we will file an IND the fourth quarter this year. It does include the opportunity to do additional studies, whether it be for new tumor indications additional studies in different lines of prostate cancer. Those are under discussion right now. And it doesn't take away from any of the work preclinically for a second ADC from the Stenafix that we said is ongoing right now, which we're hoping to target for an IND in 2024, plus a lot of other preclinical development activity that we have not discussed to date. We're very, very, very encouraged both with our cash runway and the opportunity to pursue a very robust clinical and preclinical pipeline.
spk13: Great. That makes sense. I guess I know you sometimes include risk-adjusted future milestones in your cash runway. Can you talk a little bit about how much of that potential $1 billion in milestones you're counting on when you give that runway into 2026?
spk05: Yeah, we haven't broken that down. Clearly, we make those adjustments based on real-time results. And certainly, we have the opportunity to adjust up a probability based on the fact that Santa Fe has said that they are going for regulatory approval. Obviously, we'd like to see the data. We have not seen the data on the results of the new study. But we are, at this point, we're not in a position to break out the specifics there.
spk07: This is Jim, Jonathan. I would just add to that, that historically, if we look back at the probabilities that we use for risk adjustment, we've been very conservative.
spk08: Okay, makes sense. Thanks so much. Thank you.
spk03: Thank you. Our next question comes from Sylvan Turkin with J&P Securities. Your line is open.
spk01: Yeah. Hi. Thanks for taking my question. A couple of questions on Tamarack here. The patient group that you're expecting to enroll by the end of the year or maybe early next year, will that have sufficient chemo-naive patients that that could be also an option, you know, may be better than the chemo-experienced patients? for a registrational study, or what are your options after, you know, in terms of patients' populations that you have in this phase to go on?
spk05: Well, actually, that is one of the several hard, fast enrollment criteria. They have to have been exposed to a chemotherapeutic, most likely docetaxel. In this particular study, we want to really compare the results, as I described earlier, of our previous experiences with VOBRA in a late-aligned population that is chemo-experienced. So not in this study. We are certainly interested in looking at opportunities in early-aligned therapy, including hormone-sensitive populations. Nothing is on the table right now.
spk01: Great. Thanks. That's very helpful. And then at ASCO, we saw first in human data from HANSO's ADC of directed B7H3. Are there any learnings from that that we can apply to VOVA Duo?
spk05: Yeah. I mean, I would say the most encouraging data was obviously a small data set, and they were talking about expansion and other tumor types, is that of the nine patients, with small cell lung cancer, seven had objective responses, which fits the data that Daiichi has discussed also in the small cell population. So, clearly, this is a histological type that we are certainly considering adding to the types being tested. We, as you may recall, we have only had one patient with small cell cancer in our dose escalation who actually did very well on VOBR at a lower dose. That patient was on treatment for over six months with tumor shrinkage, didn't have an objective response, but really responded well to the therapy. So clearly, that opens up for us you know, a confirmation that a small cell may be an indication, we should also pursue.
spk01: Great. Well, thanks. Thanks for taking my question.
spk03: Thank you. Thank you. Our next question comes from Boris Peeker with TD Cohen. Your line is open.
spk02: Hi. My name is Hanfei Fu for Boris Peeker. I would like to ask how confident for Loboroduo How confident are you that the two doses that you're testing will give you the ideal dose moving forward? And you think about the registration of trial, do you expect further dose modification if needed? Thank you.
spk05: So, as any experiment being conducted, you go with the data you have and you have a hypothesis and, you know, we feel that the doses we selected were the right ones. This was based on a full analysis of the data in all the expansion cohorts with regard to side effect profiles, tumor responses, pharmacokinetics. And so we tried to bookend based on what the real exposure was in patients. As I commented on earlier, the majority of patients had dose reductions. So we feel that we've picked the two doses that should give us more clarity with regard to an improved safety profile and activity profile. So as much as that can guide us, we're hoping that was the right selection and the right answer. And if we have to make modifications in some way subsequently once we get the data, we'll do it if the drug looks both good active as well as relatively safe.
spk02: Got it. Thank you for taking my question.
spk03: Thank you. As a reminder, if you'd like to ask a question, please press star 1-1. There are no further questions. I'd like to turn the call back over to Dr. Koenig for closing remarks.
spk05: Well, thank you very much, Operator, and thank you, everyone, for participating in our call today. We look forward to providing further updates, both on our clinical and preclinical pipeline in the coming months. Have a good day.
spk03: Thank you for your participation. This does conclude the program, and you may now disconnect. Everyone, enjoy the rest of your day.
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