Good afternoon. We will begin the MacroGenics 2023 fourth quarter corporate progress and financial results conference call in just a moment. All participants are in listen-only 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 Karrels, Senior Vice President, Chief Financial Officer of MacroGenics.
Thank you, Operator. Good afternoon and welcome to the MacroGenics conference call to discuss our fourth quarter 2023 financial and operational results. For anyone who has not had the chance to review these results, we issued a press release this afternoon outlining today's announcements. This release 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. Now I'd like to turn the call over to Dr. Scott Koenig, President and Chief Executive Officer of MacroGenics.
Thank you, Jim. I'd like to welcome everyone participating via conference call and webcast today. I will provide key updates on our clinical programs this afternoon, but before I do so, let me first turn the call back to Jim, who will review our financial results.
Thank you, Scott. This afternoon, MacroGenics reported financial results for the year ended December 31, 2023, which highlight our financial position. As described in a release this afternoon, MacroGenics total revenue was $58.7 million for the year ended December 31, 2023, compared to total revenue of $151.9 million for the year ended December 31, 2022. Revenue for the year ended December 31, 2023 included $29 million in revenue from collaborative and other agreements, MARGENZA and net sales of $17.9 million, and $9.8 million in contract manufacturing revenue. Our research and development expenses were $166.6 million for the year ended December 31, 2023, compared to $207 million for the year ended December 31, 2022.
This decrease was primarily due to decreased manufacturing-related costs for Vobra Duo, decreased development and clinical trial costs related to margetuximab, and decreased costs related to discontinued studies, partially offset by increased expenses related to MGC026 and MGC028 development. Scott will tell you about these two ADC product candidates in a few minutes. Our selling, general and administrative expenses were $52.2 million for the year ended December 31, 2023, compared to $58.9 million for the year ended December 31, 2022. The decrease was primarily related to decreased selling costs for MARGENZA. During the year ended December 31, 2023, MacroGenics received $100 million proceeds from the sale of our single-digit royalty interest on global net sales of TZIELD to DRI Healthcare Acquisitions, LP, in March. In addition, we received a $50 million milestone payment from Sanofi related to the achievement of a primary endpoint in a TZIELD clinical study.
Under GAAP guidelines and pursuant to Financial Accounting Standards Board Accounting Standards Codification, or ASC 470, this combined $150 million was included in other income as a "gain on royalty monetization arrangement" in 2023. Our net loss was $9.1 million for the year ended December 31, 2023, compared to a net loss of $119.8 million for the year ended December 31, 2022. Our cash equivalents and marketable securities balance as of December 31, 2023, was $229.8 million, compared to $154.3 million as of December 31, 2022. Finally, in terms of our cash runway, consistent with our prior guidance, we anticipate that our cash equivalents and marketable securities balance of $229.8 million as of December 31, 2023, 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 LORIKEET study of lorigerlimab in mCRPC, as well as our other ongoing clinical and preclinical studies. Now I'll turn the call back to Scott.
Thank you, Jim. We continue to believe our proprietary pipeline of product candidates has great promise. I will walk you through each of our key programs, including newly disclosed molecules momentarily, as well as tell you about our plans for upcoming clinical programs. But before I do that, and building on what Jim said, I'll quickly remind you that since mid-2022, through our business development efforts as well as milestone achievement, we have received $335 million of non-dilutive capital. This includes $215 million from Provention, DRI, Sanofi in connection with TZIELD, $75 million from Gilead, and $45 million from Incyte in connection with Zynyz. Okay, onto our pipeline. Vobramitamab Duocarmazine, or Vobra Duo, is our ADC designed to deliver DNA-alkylating duocarmycin cytotoxic payload to tumors expressing B7-H3. B7-H3 is a member of the B7 family of molecules involved in immune regulation.
Voger Duo was designed to take advantage of this antigen's broad expression across multiple solid tumor types. As you know, we believe that this has the attributes of an ideal cancer target. We began enrolling the Tamarack phase II study of Voger Duo under a modified study protocol during the second quarter of 2023 and completed enrollment of the study in November, months ahead of the schedule. In fact, 177 patients received Voger Duo in this study, exceeding the study design goal of 100 participants. As a reminder, Tamarack is being conducted in patients with metastatic castration-resistant prostate cancer, or MCRPC, who were previously treated with one prior antigen receptor axis targeted therapy. Participants may have received up to one prior taxane-containing regimen, but no other chemotherapy agents.
This study is being conducted to evaluate Voger Duo in patients across two experimental arms of either 2 mg/kg or 2.7 mg/kg every four weeks. In January, the Tamarack Independent Data Safety Monitoring Committee recommended continuing the study based on a protocol-specified interim analysis. Also, in early February, we submitted an abstract to ASCO that included safety data from the January data cutoff. We anticipate providing an expanded, more mature clinical update, including initial efficacy data, in the second quarter of 2024 at this meeting. In addition, we anticipate providing updated clinical data, including radiographic progression-free survival, or rPFS, the study's primary endpoint, at a conference during the second half of 2024.
We plan to expand the tumor types being evaluated in the TAMARACK trial and will enroll additional patients with non-small cell lung cancer, small cell lung cancer, melanoma, squamous cell carcinoma of the head and neck, and anal cancer. We expect to initiate dosing in these additional cohorts in mid-2024. Next, I'll update you on lorigerlimab, our bispecific tetravalent PD-1 x CTLA-4 DART molecule. We designed lorigerlimab 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. We are enrolling the LORIKEET study, a randomized phase 2 clinical trial of lorigerlimab in combination with docetaxel versus docetaxel alone in second-line chemotherapy-naïve mCRPC patients. A total of 150 patients are planned to be treated in the 2:1 randomized study. The current study design includes a primary study endpoint of rPFS.
We anticipate providing a trial update in the second half of this year. In addition, we continue to enroll patients in the phase 1/2 dose escalation study of Voger Duo in combination with lorigerlimab in patients with advanced solid tumors. We anticipate commencing a dose expansion study of this combination in mCRPC and another indication in 2024. Next up, MGD024 is our next-generation bispecific CD123 × CD3 DART molecule that incorporates a CD3 component designed to minimize cytokine release syndrome while maintaining an anti-tumor cytolytic activity and permitting intermittent dosing through a longer half-life. Our phase 1 dose escalation study of MGD024 is ongoing in patients with CD123-positive relapsed or refractory hematologic malignancies, including acute myeloid leukemia and myelodysplastic syndromes. Recall that Gilead has the option to license MGD024 at predefined decision points during the phase 1 study.
Next, I'm very excited to tell you about our growing ADC portfolio, which now includes an additional product candidate in the clinic. As I've mentioned on prior calls, we have been developing preclinical ADC molecules utilizing linker payload technologies we licensed from Synaffix. The first of these is MGC026, a clinical ADC incorporating a B7-H3 targeting antibody and a novel topoisomerase I inhibitor-based linker payload, SYNtecan E. This cleavable linker payload is based on exatecan, a clinically validated and potent camptothecin that readily combines with Synaffix's HydraSpace-based technology. We believe Synaffix's approach potentially provides advantages vis-à-vis other topoisomerase I inhibitor-based ADCs. In fact, exatecan appears to be more potent and less susceptible to multi-drug resistance mechanisms than other TOP1 inhibitors, such as SN-38 and deruxtecan.
Additionally, site-specific conjugation of SYNtecan to the normally glycosylated amino acid in the Fc domain abolishes Fc gamma receptor and mannose receptor binding, which contribute to non-targeted uptake of ADCs in alveolar macrophages and reported to be associated with lung toxicity, and therefore may provide a safety benefit for patients. The variable domain of the molecule targeting B7-H3 is the same sequence contained in Voger Duo. We recently initiated a phase 1 dose escalation study of MGC026. We view MGC026 as a complementary approach to Voger Duo for targeting B7-H3. More specifically, we believe that having distinct mechanisms of action, Voger Duo and MGC026 may address different cancers, tumor stages, or be used in combination with alternate agents or potentially with one another to enhance their clinical utility.
We remain confident in the potential of targeting the B7-H3 pathway, viewing our TOP1 inhibitor strategy as an additional valuable tool in our therapeutic repertoire. We plan to present preclinical data for MGC026 at the upcoming American Association for Cancer Research, or AACR, annual meeting next month. Here's a preview of what you'll see. In preclinical studies, MGC026 exhibited a favorable profile with potent in vivo activity toward B7-H3 expressing tumor xenografts representing a range of cancer indications. MGC026 was tolerated in cynomolgus monkeys, a relevant toxicology model, at exposure levels exceeding those required for anti-tumor activity. We look forward to showing you the data set next month. In addition, we are readying a second topoisomerase I inhibitor-based ADC, MGC028, for which we currently expect to submit an IND later this year.
MGC028 is a preclinical ADC incorporating an ADAM9 targeting antibody and the second of our ADC molecules incorporating Synaffix's novel linker payload. ADAM9, or disintegrin and metalloproteinase domain 9, is a member of the ADAM family of multifunctional type I transmembrane proteins that play a role in tumorigenesis and cancer progression and is overexpressed in multiple cancers, making it an attractive target for cancer treatment. MGC028 is the second ADAM9 target ADC that we have pursued. The first was IMGC936, a molecule with a maytansinoid payload that was advanced under a co-development arrangement with ImmunoGen, Inc., now part of AbbVie, under the 50/50 collaboration ImmunoGen-led clinical development of IMGC936. Neither MacroGenics nor AbbVie intends to further pursue development of IMGC936 as the molecule did not achieve our pre-established clinical safety and efficacy benchmarks. We plan to present preclinical MGC028 data at the upcoming AACR annual meeting in April.
As a preview, MGC028 exhibited specific dose-dependent in vivo anti-tumor activity toward ADAM9-positive CDX and PDX models, including in gastric, lung, pancreatic, colorectal, and head and neck cancers. MGC028 was well tolerated in a repeat dose non-human primate toxicology study up to 55 milligrams per kg, the highest dose level tested. Of note, ocular toxicities that are typically seen with maytansinoid payloads and which we observed in our IMGC936 cynomolgus toxicology study were not observed in the MGC028 pilot toxicology study. We plan to present more preclinical data on this asset at AACR. We currently anticipate submitting an investigational new drug or IND application for MGC028 by the end of 2024. In addition, beyond MGC026 and MGC028, we are exploring additional molecules for potential future IND submission. Stay tuned. Finally, enoblituzumab is an Fc-optimized monoclonal antibody that targets B7-H3.
Our academic collaborators have initiated an investigator-sponsored, randomized, translationally intense phase 2 investigator-sponsored study of enoblituzumab in up to 219 men with prostate cancer. The HEAT study will evaluate the activity of neoadjuvant enoblituzumab given prior to radical prostatectomy in men with high-risk localized prostate cancer. Eligible patients will undergo a pretreatment prostate biopsy and conventional imaging, both CT and bone scan, as well as PSMA PET and optional prostate MRI as per institutional preferences. To conclude, we believe we have the technical, development, and clinical expertise as well as financial resources to support our vision of developing and delivering life-changing medicines to cancer patients. We would now be happy to open the call for questions. Operator?
To ask a question, please press *11 on your telephone and wait for your name to be announced. To withdraw your question, please press *11 again.
Please stand by while we compile the Q&A roster. Our first question comes from Jonathan Chang with Leerink Partners. Your line's now open.
Hi guys. Thanks for taking my questions. First question, can you help set expectations for the preliminary TAMARACK data coming up at ASCO? And then second question, can you discuss the rationale behind expanding the TAMARACK study to include patients with non-small cell lung cancer, small cell lung cancer, head and neck, and anal cancer? What is informing this decision? Thank you. Thank you so much, Jonathan. As you've heard me previously, we had taken an evaluation of our own data that published recently by Daiichi on the DS-7300 molecule at ESMO this past fall and other data that was out there with regard to activity against prostate cancer.
And with that, as I have noted, and which we have not changed the ranges that we were seeing, just to recall, we saw about half the patients in our 3 mg per kg q3 weekly dosing of Voger Duo in our expanded approximately 40-patient cohort of about half those patients reducing PSA 50 from baseline. Given the dosings right now of 2.7 q4 and 2 q4 and with expectations if the safety is improved as we expect, we should be actually delivering as much or more of the 2.7 mgs q4 as compared to the historical treatment with the 3 mgs q3. As a result, we expect the PSA 50 to be in a similar range, somewhere between 40%-60% PSA 50 reduction. With regard to overall response rate, again, as we had previously presented, approximately a quarter of the patients achieved both confirmed and unconfirmed responses.
This was similar to that which was reported by Daiichi of 25%. So our expectation is we should be 25% or greater. With regard to rPFS, which is the primary endpoint of this study and a very important one in terms of obviously prolonging both the life and the quality of life of these patients, Daiichi reported 5.3 months of rPFS. What we have said is that we expect to have at least 6 or greater in terms of rPFS going forward. Now, with regard to the specific tumor types, we have selected for study in these expansions, again, taking advantage of our own experiences of treatment of patients with a subset of these tumors as well as the histology and expression of B7-H3 on these tumor types, we think these are very promising tumors to pursue.
I should also point out, while we are expanding into five different tumors now, we are also considering additional tumors in the future to conduct studies. Understood. Maybe just a clarifying question on that. So the decision behind expanding the study to include these other tumor types, this is based on your own internal data or data you're seeing in the competitive landscape or both? I would say both. Obviously, given the experience in small cell, for instance, where both Daiichi and Hansoh have seen very nice activity in small cell cancer, we have not had that opportunity to test it in patients with small cell cancer. So this became a very obvious one to include among the five. I would say the others were based on our own experiences as well as preclinical work that we had done against these targets.
But again, we're not even limiting it to these five. We are also considering others which would be very good opportunities for looking at the value of Voger Duo.
Thank you.
One moment for our next question. Our next question comes from
Kelsey Goodwin with Guggenheim. Your line's now open.
Oh, hey guys. Thanks for taking my question. First, regarding that ASCO abstract, what should we expect to be included in there? Will it just be safety, or will preliminary efficacy data also be in the abstract? And then secondly, could you just remind us how patient enrollment tracked throughout 2023 and how we should think about follow-up on the 177 patients in the full ASCO presentation? Thank you.
Thank you so much, Kelsey.
Because of the timing, and I'll discuss enrollment in a second, so it became quite obvious, as I pointed out, we had to do a cutoff date in January for the data submission in early February at ASCO. And as a result, we primarily relied on safety data to be included in the abstract, but also noting that our plan was to present, obviously, the clinical efficacy data as we were able to accumulate additional data closer to the time of ASCO. Again, to give you a sense of why these decisions were made in terms of the presentations, with the amendment of the original TAMARACK study, we began to enroll a few patients in the end of the second quarter.
But as it turns out, two-thirds of the patients of the 177 patients were enrolled between the second half of the third quarter and the first half of the fourth quarter. So not sufficient time was allowed to accumulate data regarding efficacy. And so that's why the decision was made to primarily include the safety data in the abstract.
Perfect. Thank you so much.
Thank you. One moment for our next question. Our next question comes from Stephen Woolley with Stifel. Your line's now open.
Yeah. Good afternoon. Thanks for taking the question. Maybe just a follow-up on the enrollment kinetics you just referenced, Scott.
Can you just, I guess, speak or characterize as to whether or not that bolus of patients that came in, second half 3Q, first half 4Q, was that primarily across newly open sites, or were those across sites where the treating investigator had had sufficient experience with the drug? Thanks for the question, Steve. So as we have spoken about it before, the initial sites with the new amendment that were opened were in the U.S., but the number of sites in the U.S. were small. The greatest number of sites were in Europe. And so with the approval of the amendments in the European sites later in the year, this created an opportunity for initiating enrollment in a large number of sites. And as we've discussed before, the rapidity of enrollment was far beyond what we expected.
In fact, we ended up probably - and don't hold me to the exact number - approximately a third of the sites that we intended to open were never opened because of the fast enrollment later in the year on these newly open sites. So U.S. sites continued to enroll, but just because of the proportion that were in Europe compared to Asia and the U.S., the majority got enrolled in Europe in that bolus in the second half of the year.
Okay. So just to clarify, these were new sites that came online in Europe, or were these sites that had already enrolled sufficiently?
No. Well, again, remember, the regulatory timing for getting the amendment through was after that of the U.S. So it occurred after the U.S. started to enroll these patients. The majority came in Europe. It was just the sheer numbers of sites there.
Okay.
Understood. Then I guess in kind of basing off the 2.7 and 2.0 q4W doses, I mean, I know you just referenced 2.7. Is it safe to say that you guys have settled on a go-forward dose at this point? And would there be any need to evaluate both dosing regimens as you expand into some of these additional tumor types?
I think it's too early to have a final answer on that. Clearly, we want to continue to follow the safety as well as the ultimate activity. And as I alluded to in my earlier remarks, the expectation, for instance, rPFS won't occur after the mid-year. So I think we'll have to see the totality of data to be definitive about which one goes forward.
But as pointed out in the comments earlier, the Data Safety Monitoring Committee in January looking at the safety at the time and the activity at the time that was available in January concluded that both doses should continue. So I think it'll be a decision that we will arrive at by mid-year.
Okay. And last question, is the maturity of that rPFS statistic rate limiting to your ability then to initiate these additional dose expansion cohorts?
No. No. That will not slow that down at all. We are working both from a regulatory advantage and operationalizing this so that we can get going by mid-year.
Thank you. One moment for our next question. Our next question comes from Etzer Darout with BMO Capital Markets. Your line's now open.
Great. Thanks for taking the question. Just a couple for me here too.
Just thinking about the monotherapy Voger Duo study, just if you can maybe start just describing what your thoughts are around sort of the pivotal path or development for that in terms of monotherapy or in combination based on what you're observing from TAMARACK so far and whether or not any of sort of the recent datasets that have come out in prostate sort of maybe changes the dynamic of how you're thinking about pivotal development of Voger Duo. Thanks.
Thanks, Etzer. Again, I won't comment on the activity from the TAMARACK study. That will come out at ASCO.
But obviously, looking at the landscape, what is necessary to get a high confidence for a regulatory approval, I think we are in a fortunate position now that with the 177 patients dosed, and what I had commented on earlier, that we had a sizable number of patients that were both chemotherapy experienced as well as chemotherapy naive in this study. So while we entered into the study with the idea that any phase 3 study would likely to be done in a post-chemo experienced population, we have now changed that view that clearly, in a chemo-naive population, if both the efficacy and the safety warrant it, that seems to be a very suitable population, an early-aligned population to pursue. And we can also pursue the late line as well.
So we still have everything open at this point, but until we have the more mature data, we won't make that decision.
Great. Thank you.
Thank you. One moment for our next question. Our next question comes from Yigal Nochomovitz with Citigroup. Your line's now open.
Yeah. Hi, Scott and team. Thank you. Just to clarify, so for the ASCO abstract, it seems like it's going to be focused on the safety. But in the presentation at the conference itself, should we expect to see any initial radiographic PFS data or not?
So thank you very much, Yigal. So clearly, we will show as much efficacy data as possible at the cutoff time. Likely, this is going to be a month, a month and a half before the submission is ready for presentation. So as you know, the meeting itself is the end of May.
I would presume that they will require us to have the material prepared by mid-May. So my expectation would be that there would be a cutoff date, sort of late March, early April. With that, we will clearly have a lot of data available on patients that have been dosed for many months. So that would include, obviously, PSA50 reductions, would look at overall response rates, a full dataset, obviously, a full dataset with safety. With regard to rPFS, we'll have to see how many patients have been dosed for how long to see if we can do some at least preliminary cuts on rPFS. It may require us to wait until the next meeting in the early fall to update that. But we certainly will provide as much data as we can.
Okay. Thanks. And then a moment ago, you referenced the PFS of at least 6 months.
This would be the expectation. I'm just wondering, for some of these other comps out there, which we're all familiar with, the CAR-T trial and the Vision trial for cabazitaxel and Pluvicto, respectively, as we know, those were slightly higher, around 8 and 8.5 months. Are those reasonable expectations or not for what one should expect for TAMARACK?
Yeah. No. And again, it'll depend on whether we go into the chemo-naive population or chemo-experienced and how late-line we would do those studies. So that's why it's a little broad. If you look at the controls for the studies that you described, it obviously will depend on what the controlled drug is. The typical ones, for instance, in the chemo-naive population was docetaxel for around 8 months. And similarly, in the activity for the CAR-T study was about 8 months.
So yeah, I think that, again, which population you ultimately look at would require more than just 6. It would be 8 or higher. And certainly, I just don't want to limit what this drug could potentially achieve. We just don't know the answer yet. I was just pointing out the base minimum, particularly on a later-line population, would be at least 6 months.
Thank you.
One moment for our next question. Our next question comes from Jon Miller Your line's now open.
Hi guys. Thanks for taking the question. I would love to ask about those additional indications that you're moving Voger Duo into in the TAMARACK study. Do you have any additional data from any of those indications in the phase one expansion that we haven't seen at this point? And obviously, we've seen a lot of interest in these indications with B7-H3 more broadly.
But previously, you had said you were prioritizing prostate for bandwidth reasons and to sort of competitively be in white space there. So can you talk us through a little bit about what changed and why your decision to chase after those indications coming now? And then secondly, I'd love if you could go in a little bit deeper into your differentiation of the new 026 B7-H3 ADC from the other TOPO-1 payload ADCs against the same target that are in development.
Thanks so much, Jon. Yes. So as you well know, while we've been focusing on prostate cancer because of bandwidth, which is correct, as you may recall, about two years ago, we were intending to do further expansion in melanoma but had to cut back because of cash at that time. So that was clearly a population that we had strong interest in.
We also had seen in the expansion studies very good activity in other indications. So things like non-small cell lung cancer became a great opportunity to us, activity in head and neck cancer as well. We have not had any experience with anal cancer with the Voger Duo. And small cell is obvious, as I alluded to before, based on others' experience there. So those were the initial reasoning behind going after this. And we believe that with the improved potential safety profile of the new dosing regimen, these patients with these other cancers will be able to stay on drug longer to have potentially good outcomes. And that's why we're looking to expand into those indications.
Now, with regard to 026, as I pointed out, this is a great opportunity for us to really take an answer to important questions and a great opportunity for treating a wide range of cancers. As you are well aware, different chemotherapies work in different tumors. Combination chemotherapy, as well as combinations with other modalities, is the typical standard of treatment for cancer. So given that we've had wonderful experience with the variable domain of Voger Duo in its activity and what we believe could potentially be a superior TOPO-1 inhibitor payload based on the Synaffix profile, and as I pointed out, from various vantage points, including increased activity potency, a less susceptibility to efflux, multidrug resistance, better cell permeability, bystander effect, and the fact, as Daiichi has pointed out, many of the interstitial lung disease complications, they are ascribing to binding to alveolar macrophages.
By the fact that this Synaffix platform eliminates the binding through Fc receptors as well as mannose receptors, one should potentially have the ability to reduce an ILD effect with a topo-1 inhibitor. So from all these vantage points and from all the things that I described earlier, looking at the ability to treat with Voger Duo, looking at potential combinations with 026 down the line, looking at treatment of different tumors, I think this provides us with a great opportunity.
Thanks, Scott. Have we seen all of the data from the various other indications that you were looking at in phase 1 before you put those on hold?
W e have not. We have not. Head, neck, and non-small cell? Yeah. We have not. And at a future date, we will put all that data together for publication. So yes, at a future time.
But there is data yet to be presented.
Thank you.
One moment for our next question. Our next question comes from Kaveri Pohlman with BTIG. Your line's now open.
Yeah. Good evening. Thanks for taking my questions. For the upcoming readout, you will have Voger Duo data for both docetaxel-naive and experienced patients. But since you are not going to have mature rPFS data till second half, how are you thinking about making a decision on where to go in terms of a phase III trial?
Well, good question, Kaveri. Clearly, there will be other metrics that we will be looking at beyond just the rPFS. But there will be a certain number of those patients that will have advanced. We certainly would like to have the full dataset to make a final decision.
But I think by mid-year, we'll know quite well if we're on track for moving forward to a phase III point. And obviously, we don't want to wait till the last minute because operationally, there's a lot to do, not the least of which is engagement with regulatory agencies to describe plans and get feedback there. So we would just want to be as aggressive as possible once we have at least a large body of data available to us by mid-year.
All right. That's helpful. And then my second question is regarding MGD024. Any color on when you expect to complete the phase I trial? And how much time Gilead will have to make a decision to opt in once you provide the data? So with regard to 024, as I was commenting, we are in the middle of dose escalation.
As you know, for T-cell redirected killing mechanisms for bispecifics, the regulatory agencies have been very strict on the rate in which one can do the dose escalation. And so that's really been the limiting factor here. So I can't tell you what the end will be. We are through many cohorts of groups and continuing up as quickly as possible. With that, Gilead hasn't until a short period of time after we present the full phase I data to them to opt in on the program. So clearly, there's still time. And clearly, during the dose escalation, if they decide they want to opt in, they have the right to do so.
Thank you. One moment for our next question. Our next question comes from Tara Bancroft with TD Cowen. Your line's now open.
Hi. Good afternoon.
I understand the rationale for potentially enabling broad development of Voger Duo with the inclusion of pre-taxane patients. But I'm curious what details you will give us in the presentation about baseline characteristics? In particular, will you include time to progression on initial therapy? I have, depending on your answer, a follow-up on that.
We will clearly try to provide as detailed as possible on that population. I don't know how many of the patients we have that data in the database in terms of their time to progression. We'll have to go back and look at that and update you at a future date. I just don't know that off the top of my head of how many of those patients we have that data.
Okay. Yeah. Thanks. You're not excluding rapid progressors, right?
If not, how would you expect them to affect rPFS? Is that where your 6-month versus 8-month expectations come from, are those patients? I think you've hit the nail on the head. That's why I'm trying to give a little bit broad brush strokes on that on understanding the patients. Rapid progressors are allowed here. As we opened up, for instance, the study, the original design of the study required at least 12 months of treatment on an ARAT to be qualified for enrollment in our study. When we removed that requirement, clearly, patients who had very short courses and progressed quickly, as well as very newly diagnosed patients before they got their initial treatment presented as metastatic disease, these are the type of patients that could have a much more aggressive course and a shorter course to any treatment.
So that is why we have gotten actually also feedback from KOLs that having a baseline of six months is not unreasonable for that type of patient.
Okay. Thank you so much.
Thank you. One moment for our next question. Our next question comes from Courtney Kowalski with Barclays. Your line's now open.
Hi. This is Peter Lawson from Barclays. So just a couple of questions. Firstly, in the abstract, will we see safety that's broken out by discontinuation rates and/or side effects such as hand-foot, pleural effusion and never got a follow-up?
Peter, you will have the discontinuation rates as of that cut of January data. With regard in the abstract itself, I don't recall specifically how deep in terms of the breakdown of the AEs were. I'll have to get back to you on that. Good. Thank you.
Then in the TAMARACK study, have patients been exposed to radiopharmaceuticals such as Pluvicto? And will you be able to break that out eventually?
Yeah. Unfortunately, they are allowed in the study. But given the timing of the study and as I pointed out, the majority of these patients came from Europe, the actual availability of Pluvicto and the timing didn't work out to get those Pluvicto progressors and experienced patients there. We expect a few of them from the US but very small numbers there.
Okay. And then just a quick question for Jim on the puts and takes around the cash guidance, just with the expansion of the B7-H3 clinical trials. Kind of, I guess, that's a negative for cash. But what are the puts and takes we should kind of be thinking about for you to maintain that cash guidance?
Yeah. Thanks, Peter.
Thanks for the question. So our guidance of cash runway into 2026 reflects the additional cohorts under the TEMRX umbrella, the additional Voger Duo cohorts. So everything we're talking about, all of these studies that we're currently running and talking about running are all included as part of our guidance.
Gotcha. Are there any additional inflows of cash you're thinking through to kind of counterbalance that? Or was that always in the cash guidance?
Peter, I'm sorry. Could you repeat the question, please?
Oh, is there any additional cash inflows that you're thinking through? Or were those cohorts always in the cash guidance?
Those cohorts are new to the guidance. There have been some savings. There's always the possibility of additional business development activities.
And of course, with $1 billion in milestones hanging out there related to both TZIELD and Zynyz, of which we've handicapped significantly, we would anticipate recognition of some of those over the next couple of years.
Perfect. Thank you so much.
And there were some additional revenues coming in that weren't anticipated originally that are part of this guidance, so.
Great. Okay. Thank you so much. Thanks for the clarity.
Thank you. One moment for our next question. Our next question comes from Silvan Tuerkcan with Citizens JMP. Your line's now open.
Yeah. Thank you. Thanks for taking my question. And congrats on the progress. Maybe piggybacking a little bit on a previous question, what's the bar for the safety profile in the abstract or also at the ASCO presentation versus the safety profile that we've seen on the lower doses?
I'm asking in particular maybe on the grade three or higher issues that we've seen with the hand-foot syndrome and perhaps neutropenia. Can you just comment on what you're trying to improve? And is there any data that makes you confident in the future here? Thank you. And I have a follow-up.
Sure, Silvan. I just want to correct you. Our concern was not grade three hand-foot. Obviously, we want to avoid that at all. Though the incidence of that was quite low, the issue was that patients with grade two where they were experiencing pain would be electing to come off treatment despite the fact that they were having antitumor effects. And so number one is the most important is that if we can decrease the incidence totally.
And then for those that have with a reduced incidence, converting or preventing them from going from grade one to grade two would be what our goal is there. With regard to the neutropenia, clearly, that is something most likely due to free toxin getting to the bone marrow. But again, this was a situation where it was largely a laboratory value. It did not result in increased infections or febrile neutropenia. And so this is mostly handled by holding the drug or stopping the drug. And again, if we can reduce that both in terms of incidence and grade, I think that will be better. But that wasn't as concerning to the treating physicians in managing these patients.
Great. Thank you. And maybe about the LORIKEET study, will we get data from that study this year?
Maybe how does that relate to your late-stage monotherapy plans if you get data from the combo of Voger Duo and lorigerlimab?
With regard to the timing of this, we'll provide, as I said earlier, an update on the study. It ultimately will depend on the speed in which we can enroll these patients. Clearly, over the next two months, will we exceed the plan? Or will it take longer, meaning later in the year, to get full enrollment of the study? If it's the latter, it's more likely we'll have a more fulsome update in early 2025. But again, we'll be able to give you a little bit more guidance later in the year based on enrollment rates. With regard to the success in this trial, clearly, we're testing this in the chemo-naïve population in combination with docetaxel.
I think that if that trial is successful, it's a great problem to have if the Voger Duo pans out also in that same line of therapy. I should also say that we are not eliminating the possibility that we're going to look at LORIKEET. I'm sorry, LORIKEET in late-line prostate cancer. That is certainly a possibility to consider. But as I have said before, we are also going to look at LORIKEET outside of prostate cancer going forward. So it's just too early to make a decision on registration studies until we have the data.
Great. Thank you.
Thank you. As a reminder to ask a question, please press star one on e on your telephone and wait for your name to be announced. To withdraw your question, please press star one one again. Our next question comes from Yigal Nochomovitz with Citigroup. Your line's now open.
Oh, hi. Thank you so much for taking the follow-up. Scott, I just had a quick follow-up on TEMRX. It's unusual that you see a trial that's 77% over-enrolled relative to the target and enrolled very quickly. Could you just comment on some of the factors that resulted in the heavy over-enrollment and as well as the speed to which it was over-enrolled? Thanks.
Yeah. So Yigal, with regard to our decision on letting so many more patients into the study, we felt it was not ethical for us to not allow these patients into the study if they had already been in screening and passed the screening requirements. And so we felt that we should do this because the patients made a and the investigators made great efforts to find patients in the study.
As I was commenting on earlier, the surge of enrollment, once we had the go-aheads from the amended protocol in Europe, there was tremendous enthusiasm to join the study. And I'm sure there are a lot of different reasons. As I was pointing out, some of the amendments included the fact that we didn't require 12 months of treatments on an ARAT. And so patients who were progressing quickly were able to join the study. And they probably did not have much in terms of other alternatives. There also, it turns out, to be a large number of patients for varying reasons, whether they're not qualified to go on docetaxel or chemotherapeutic or they choose not to. I think we attracted a large number of those patients into the study that allowed us to have a very sizable subpopulation of chemo-naive patients.
Got it. Thank you very much. Thank you.
I'm showing no further questions at this time. I would now like to turn it back to Scott Koenig for closing remarks.
Well, thank you very much for participating in the call today. We look forward to, obviously, updating you at ASCO in the near term and talk to you at future times on earnings calls and in other venues. Thank you very much.
This concludes today's conference call. Thank you for participating. You may now disconnect.