MacroGenics (NASDAQ:MGNX), a biopharmaceutical company focused on discovering and developing innovative monoclonal antibody-based therapeutics for the treatment of cancer, reported a decrease in annual total revenue to $58.7 million in 2023 from $151.9 million in 2022. Despite this, the company significantly reduced its net loss to $9.1 million in 2023 from $119.8 million in the previous year.
MacroGenics' cash reserves have grown, with a balance of $229.8 million as of December 31, 2023, compared to $154.3 million at the end of 2022. The company expects its current financial resources to fund operations into 2026. MacroGenics provided updates on several clinical trials, including the TAMARACK, LORIKEET, and studies of MGD024, MGC026, and MGC028.
Key Takeaways
- MacroGenics' total revenue for 2023 was $58.7 million, a decrease from $151.9 million in 2022.
- The company's net loss improved to $9.1 million in 2023, down from $119.8 million in 2022.
- Cash reserves as of December 31, 2023, were reported at $229.8 million.
- The financial position is expected to support operations into 2026.
- Clinical updates include the TAMARACK and LORIKEET studies, and Phase 1 studies of MGD024, MGC026, and plans for an IND submission for MGC028.
Company Outlook
- MacroGenics anticipates its cash balance to extend its cash runway into 2026.
- The company plans to present preclinical data for MGC026 and submit an IND for MGC028 later in the year.
- Additional molecules are being explored for potential future IND submissions.
Bearish Highlights
- Total revenue saw a significant decrease in 2023 compared to 2022.
Bullish Highlights
- The company's net loss has substantially decreased.
- The cash position has improved, suggesting a more stable financial outlook.
- Clinical trials are progressing with various studies showing potential.
Misses
- The company has not yet settled on a final dosing regimen for their drug.
- Mature progression-free survival (rPFS) data will not be available until the second half of the year.
Q&A Highlights
- Enrollment for clinical trials is proceeding faster than anticipated, particularly in Europe.
- Decisions about Phase III trials for Vobra Duo will be based on midyear data.
- Gilead (NASDAQ:GILD) has a limited time to opt in on the MGD-024 program after Phase I data presentation.
- The TAMARACK study included rapid progressors, which may impact progression-free survival metrics.
- The safety profile and the potential for combination therapies are under continuous evaluation.
MacroGenics has outlined a strategic focus on advancing its clinical programs, with several studies in progress. The company remains committed to its research and development efforts, with the goal of offering new therapeutic options for cancer patients. Further updates on the company's clinical trials and financial position are expected to be provided at upcoming conferences and future earnings calls.
InvestingPro Insights
MacroGenics (MGNX) has shown a dynamic financial and stock performance over the recent period. Here are some insights based on real-time data from InvestingPro and InvestingPro Tips that could be crucial for investors:
InvestingPro Data:
- The company's market capitalization stands at $1.27 billion, reflecting its current valuation in the market.
- MacroGenics has a Price-to-Earnings (P/E) ratio of 25.54 when adjusted for the last twelve months as of Q3 2023, indicating how much investors are willing to pay per dollar of earnings.
- The stock has experienced a significant price total return of 135.48% over the last three months, showcasing a strong performance in the short term.
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Full transcript - Macrogenics (MGNX) Q4 2023:
Operator: Good afternoon. We will begin the MacroGenics 2023 Fourth Quarter Corporate Progress and Financial Results Conference Call in just a moment. [Operator Instructions] At this point, I will turn the call over to Jim Karrels, Senior Vice President, Chief Financial Officer of MacroGenics.
Jim Karrels: Thank you, operator. Good afternoon, and welcome to 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 2 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 reviews 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.
Scott Koenig: 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.
Jim Karrels: Thank you, Scott. This afternoon, MacroGenics reported financial results for the year ended December 31, 2023, which highlight our financial position. As described in the 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 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 2 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 addition, we received a $50 million milestone payment from Sanofi (EPA:SASY) (NASDAQ:SNY) related to the achievement of a primary endpoint in a TZIELD clinical study. Under GAAP guidelines and pursuant to Financial Accounting Standards Board’s 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, 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, 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 2 TAMARACK clinical trial, the Phase 2 LORIKEET study of lorigerlimab mCRPC, as well as our other ongoing clinical and preclinical studies. And now I'll turn the call back to Scott.
Scott Koenig: Thank you, Jim. We continue to believe our proprietary pipeline of product candidates has great promise, and we'll 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 (NASDAQ:INCY) in connection with ZYNYZ. Okay, on to 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. Vobra 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 2 study of vobra duo under a modified study protocol during the second quarter of 2023 and completed enrollment of this study in November months ahead of the schedule. In fact, 177 patients received vobra duo in the 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 have previously treated with one prior antigen receptor access targeted therapy. Participants may have received up to one prior taxing containing regimen but no other chemotherapy agents. This study is being conducted to evaluate vobra duo in patients across two experimental arms of either 2 mgs/per kg or 2.7 mgs/per kg every 4 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 by 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 of randomized Phase 2 clinical trial of lorigerlimab in combination with docetaxel versus docetaxel alone in second-line, chemotherapy-naive 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 vobra 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 by CD3 DART molecule that incorporates CD3 component designed to minimize cytokine-release syndrome, while maintaining 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 1 inhibitor based linker payload SYNtecan E. This cleavable linker payload is based on exatecan, a clinically validated and potent cancer SCCHN [ph] that readily combines with Synaffix hydrospace technology. We believe Synaffix's approach potentially provides advantages vis-a-vis other topoisomerase 1 inhibitor-based ADCs. In fact, exatecan appears to be more potent and less susceptible to multidrug-resistance mechanisms than other type 1 inhibitors, such as SN-38 and deruxitecan. Additionally, site-specific conjugation of SYNtecan to the normally glycosylated amino acid in the FC domain abolishes FC gamma receptor and manhouse receptor binding, which contribute to nontargeted uptake of ADCs in our 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 vobra duo. We recently initiated a Phase I dose escalation study of MGC026.. We view MGC026 as a complementary approach to vober duo for targeting B7-H3. More specifically, we believe that having distinct mechanisms of action, vober duo and MGC 026 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 Topo 1 inhibitor strategy as an additional valuable tool in our therapeutic repertoire. We plan to present preclinical data for MGC O26 at the upcoming American Association for Cancer Research or AACR Annual Meeting next month. Here's is a preview of what you'll see. In preclinical studies, MGC026 exhibited a favorable profile with potent in vivo activity to our B7-H3 expressing tumor xenografts representing a range of cancer indications. MGC0026 was tolerated in cinemalogous monkeys, a relevant toxicology model at exposure levels exceeding those required for antitumor activity. We look forward to showing you the data at next month. In addition, we are readying a second topoisomerase 1 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 metalloprotease domain 9 is a member of the ADAM family of multifunctional Type 1 transmembrane proteins that play a role in tumor genesis 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. So first was IMGC936, a molecule with a maytansinoid payload that was advanced under a co-development arrangement with ImmunoGen (NASDAQ:IMGN), Inc. now part of AbbVie (NYSE:ABBV). Under the 50-50 collaboration, ImmunoGen led clinical development of IMGC936, neither MacroGenics nor AbbVie intent to further pursue development of IMGC936 as the molecule did not receive our preestablished 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 antitumor 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 nonhuman 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 cinemologous [ph] 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 II 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?
Operator: [Operator Instructions] Our first question comes from Jonathan Chang with Leerink Partners. Your line is now open.
Jonathan Chang: 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 melanoma, head and neck and anal cancer, what is informing this decision? Thank you.
Scott Koenig: 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 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 of Q3 weekly dosing of vobra duo in our expanded approximately 40-patient cohort of about half those patients reducing PSA50 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 mg Q4 as compared to historical treatment with the 3 mgs Q3. As a result, we expect the PSA50 to be in a similar range somewhere between 40% and 60% PSA50 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, and 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 the 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. And 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 four 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.
Jonathan Chang: Understood. Maybe just a clarifying question on that. So the decision kind 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?
Scott Koenig: I would say both. Obviously, given the experience in small cell, for instance, where both Daiichi and Hanso [ph] 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, I'm not -- 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 vobra duo.
Operator: Thank you. One moment for our next question. Our next question comes from Kelsey Goodwin with Guggenheim. Your line is now open.
Kelsey Goodwin: Hey, guys. Thanks for taking my question. First, regarding the 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.
Scott Koenig: 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 cut-off 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, we -- 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.
Kelsey Goodwin: Perfect. Thank you so much.
Operator: Thank you. One moment for our next question. Our next question comes from Stephen Willey with Stifel. Your line is now open.
Stephen Willey: 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 those -- that bolus of patients that came in second half, 3Q, first half 4Q. Was that primarily across newly opened sites or were those across sites where the treating investigator had sufficient experience with the drug?
Scott Koenig: 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. And in fact, we ended up probably -- and don't hold me to the exact number, approximately a third of the size that we intended to enroll -- open were never open because of the fast enrollment later in the year on these newly opened sites. So U.S. sites continue to enroll, but just because of the proportion that was 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.
Stephen Willey: Okay. So just to clarify, these were new sites that came online in Europe? Or were these sites that had already enrolled...
Scott Koenig: No, these are -- 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.
Stephen Willey: Okay. Understood. And then I guess, in kind of baking 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?
Scott Koenig: 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 to the -- after the midyear. So I think we will 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 will be a decision that we will arrive at by midyear.
Stephen Willey: Okay. And then last question, is the maturity of that rPFS statistic rate limiting to your ability then to initiate these additional dose expansion cohorts?
Scott Koenig: 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 midyear.
Operator: Thank you. One moment for our next question. Our next question comes from Etzer Darout with BMO Capital Markets. Your line is now open.
Etzer Darout: Great. Thanks for taking the question. Just a couple for me here, too. Just thinking about the monotherapy vobra duo study. Just if you can maybe start - just describing what your thoughts around sort of the pivotal path for 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 data sets that have come out in prostate sort of maybe changes the dynamic of how you're thinking about pivotal development of vobra duo? Thanks.
Scott Koenig: 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 have 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 III study would likely to be done in a post chemo experience population, we have now changed that view that, clearly, in a chemo-naive population if both the efficacy and the safety warranted, that seems to be a very suitable population, an early along 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.
Operator: Thank you. One moment for our next question. Our next question comes from Yigal Nochomovitz with Citigroup. Your line is now open.
Yigal Nochomovitz: Hi, Scott and Jim. Thank you. Just to clarify. So for the ASCO abstract, it seems like you're just 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?
Scott Koenig: 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 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 data set, obviously, a full data set with safety. With regard to our 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.
Yigal Nochomovitz: 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 CARD trial and the VISION trial for cabazitaxel and pluvicto, respectively. As you know, those were slightly higher around 8 and 8.5 months. Are those reasonable expectations or not for what one should expect for TAMARACK?
Scott Koenig: Yes. And again, it will depend on whether we go into the chemo-naive population or chemo experience 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, for in the chemo-naive population was docetaxel for around 8 months. And similarly in the activity for the CARD study was about 8 months. So yes, 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 were just pointing out the base minimum particularly on a later line population would be at least 6 months.
Operator: Thank you One moment for our next question. Our next question comes from John Miller with Evercore. Your line is now open.
John Miller: Hi, guys. Thanks for taking the question. I would love to ask about those additional indications that you're moving vobra duo into - in the TAMARACK study. Do you have any additional data from any of those indications in the Phase I 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 out for 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 [ph] ADC from the other topo1 payload ADCs against the same targets that are in development?
Scott Koenig: Thanks so much, John. 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 2 years ago, we were intending to do an expansion as - further expansion in melanoma, but had to cut back because of cash at that time. So that was clearly a population that we had a 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 vobra duo and small cell is obvious as I alluded to before, based on others' experience there. So those are 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 important - answer important questions and a great opportunity for treating a wide range of cancers. As you are well aware, different chemotherapies work in different tumors and combination chemotherapy as well as combinations with other modalities is the typical standard of treatment for cancer. And so given that we've had wonderful experience with the variable domain of vobra duo in its activity and what we believe to potentially be a superior topo1 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 by standard effect. And the fact, as Daiichi has pointed out, many of the institutional lung disease complications, they are ascribing to binding to alveolar macrophages and by the fact that this Synaffix platform eliminates the binding through Fc receptors, as well as mannose receptors, one shouldn't potentially have the ability to reduce a ILD effect with a topo1 inhibitor. So from all these vantage points and from all the things that I described earlier, looking at the ability to treat with vobra 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.
John Miller: 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?
Scott Koenig: Yes, 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.
Operator: Thank you. One moment for our next question. Our next question comes from very Kaveri Pohlman with BTIG. Your line is now open.
Kaveri Pohlman: Good evening. Thanks for taking my questions. For the upcoming readout, you will have vobra duo data for both docetaxel naive and experienced patients. But since you are not going to have mature rPFS data until second half, how are you thinking about making a decision on where to go in terms of a Phase III trial?
Scott Koenig: Well, a 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 data set to make a final decision. But I think by midyear, 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 midyear.
Kaveri Pohlman: All right. That's helpful. And then my second question is regarding MGD-024. 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?
Scott Koenig: 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 what the most -- 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, if they -- during the dose escalation, if they decide they want to opt in, they have the right to do so.
Operator: Thank you. One moment for our next question. Our next question comes from Tara Bancroft with TD Cowen. Your line is now open.
Tara Bancroft,: Hi, good afternoon. So I understand the rationale for potentially enabling broad development of vobra duo with the inclusion of Pretaxane [ph] patients. But I'm curious what details you will give us in the presentation about baseline characteristics. And in particular, will you include time to progression on initial therapy? And I have -- depending on your answer, a follow-up on that.
Scott Koenig: So we will clearly try to provide a detailed 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 up at top of my head of how many of those patients we have that data.
Tara Bancroft,: Okay. Yes, thanks. So you're not excluding rapid progressors, right? And if not, how would you expect them to affect rPFS? Like is that where your 6th month versus 8 month expectations come from are those patients?
Scott Koenig: I think you've hit the nail on the head, and that's why I'm trying to give a little bit broad brush strokes on that on understanding the patients. The 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. And when we remove 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 6 months is not unreasonable for that type of patient.
Tara Bancroft,: Okay. Thank you so much.
Operator: Thank you. One moment for our next question. Our next question comes from Courtney Kowalsky with Barclays (LON:BARC). Your line is now open.
Pete Lawson: This is Pete Lawson from Barclays. So just a couple of questions. Firstly, in the abstract, where we see safety that's broken out by discontinuation rates and/or side effects such as [indiscernible] And then I've got a follow-up.
Scott Koenig: 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 have to get back to you on that.
Pete Lawson: Got you. Thank you.
Scott Koenig: And then in the TAMARACK study, patients been exposed to radiopharmaceuticals such as Pluvicto.
Pete Lawson: And will you be able to break that out eventually?
Scott Koenig: Yes. 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 vobra duo [ph] and the timing didn't work out to get those Pluvicto progressors and experienced patients there. We expect a few of them from the U.S., but very small numbers there.
Pete Lawson: 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 can be thinking about for you to maintain that cash guidance?
Jim Karrels: Yes. Thanks, Peter. Thanks for the question. So our guidance of cash runway into 2026 reflects the additional cohorts under the TAMARACK umbrella, the digital vobra duo cohorts. So everything we're talking about, all of these studies that we're currently running. And talking about running are included as part of our guidance.
Pete Lawson: Got you. And are there any additional inflows of cash you're thinking through to kind of counterbalance that? Was that always in the cash guidance?
Jim Karrels: Peter, I'm sorry, could you repeat the question, please?
Pete Lawson: Or is there any additional cash inflows that you're thinking through? Or were those cohorts always in the cash guidance?
Jim Karrels: Those cohorts are new to the guidance. There have been some savings. There's always a possibility of additional business development activities. And of course, with $1 billion milestones hanging out there related to both TZIELD and ZYNYZ, which we've handicapped significantly, we would anticipate recognition of some of those over the next couple of years.
Scott Koenig: And there were some additional revenues coming in that weren't anticipated originally that are part of this guidance. So...
Pete Lawson: Great, okay. Thank you so much. Thanks for the clarity.
Operator: Thank you. One moment for our next question. Our next question comes from Silvan Tuerkcan with Citizens JMP. Your line is now open.
Silvan Tuerkcan: Thank you. Thanks for taking my question and congrats on the progress. Maybe piggybacking a little bit on the 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 older doses? And I'm asking, in particular, maybe on the grade 3 or higher issues that we've seen with the [indiscernible] Can you just comment on what you're trying to improve? And is there any bar that makes you confident in the future here? And I have a follow-up.
Scott Koenig: Sure, Silvan, I just want to correct you. Our concern was not Grade 3 hand foot. Obviously, we want to avoid that at all though the incidence of that was quite low. The issue was that patients would either with Grade 2 where they have 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 we can decrease the incidence totally. And then for those that have -- with a reduced incidents converting or preventing them from going from Grade 1 to Grade 2 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 is a situation where it was largely a laboratory value. It did not result in increased infections or federal 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 incidents and grade, I think that will be better. But that wasn't as concerning to the treating physicians in managing these patients.
Silvan Tuerkcan: Thank you. And maybe about the LORIKEET study, will we get data from that study this year? And maybe how does that relate to your late-stage monotherapy plans if you get data from the combo of what we do in lorigerlimab?
Scott Koenig: With regard to the timing of this, we'll provide, as I said earlier, a update on the study. It ultimately will depend on the speed in which we can enroll these patients clearly over the next 2 months, we -- 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 that we'll have a more fulsome update in early '25. 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-naive population in combination with docetaxel. I think that if that trial is successful, it's a great problem to have if the vobra 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 and Lorigerlimab 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 Lorigerlimab outside of prostate cancer going forward. So it's just too early to make a decision on registration studies until we have the data.
Operator: Thank you. [Operator Instructions] Our next question comes from Yigal Nochomovitz with Citigroup. Your line is now open.
Yigal Nochomovitz: Thank you so much for taking the follow up. Scott, I just had a quick follow-up on TAMARACK, 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 overenrolled. Thanks.
Scott Koenig: Yes. So go with regard to our decision on letting so many more patients into the study as 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 ahead 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 treatment on an ARAD 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.
Operator: 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.
Scott Koenig: 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 at on earnings calls and in other venues. Thank you very much.
Operator: This concludes today's conference call. Thank you for participating. You may now disconnect.+
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