Q4 2023 MacroGenics Inc Earnings Call
Participants
Jim Karrels; SVP, CFO & Secretary; MacroGenics, Inc.
Scott Koenig; President, CEO & Director; MacroGenics, Inc.
Jonathan Chang; Analyst; Leerink Partners LLC
Kelsey Goodwin; Analyst; Guggenheim Partners, LLC
Stephen Willey; Analyst; Stifel, Nicolaus & Company, Incorporated
Etzer Darout; Analyst; BMO Capital Markets
Yigal Nochomovitz; Analyst; Citigroup Global Markets Inc.
Jon Miller; Analyst; Evercore ISI
Kaveri Pohlman; Analyst; BTIG, LLC
Tara Bancroft; Analyst; TD Securities (USA) LLC
Peter Lawson; Analyst; Barclays Capital Inc.
Silvan Tuerkcan; Analyst; Citizens JMP Group, LLC
Presentation
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 James Karrels, Senior Vice President, Chief Financial 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 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.
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 31st, 2023 which highlight our financial position as described in our 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 31st, 2022. Revenue for the year ended December 31st, 2023 included $29 million in revenue from collaborative and other agreements, margins 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 31st, 2023, compared to $200.7 million for the year ended December 31st, 2022. This decrease was primarily due to decreased manufacturing related costs from overdue O, 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 31st, 2023 compared to $58.9 million for the year ended December 31st, 2022. The decrease was primarily related to decreased selling costs for MARGENZA. During the year ended December 31st, 2023, MacroGenics received $100 million proceeds from the sale of our single digit royalty interest on global net sales of Teva's yield to 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 Standard Board Accounting Standards Codification or ASC 470, this combined, $150 million was included in other income as a quote, gain on royalty monetization arrangement, unquote in 2023. Our net loss was $9.1 million for the year ended December 31st, 2023 compared to a net loss of $119.8 million for the year ended December 31st, 2022. Our cash, cash equivalents and marketable securities balance as of December 31st, 2023 was $229.8 million compared to $154.3 million as of December 31st, 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 31st, 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 lower acute study of lorigerlimab in 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. 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 prevention, DRI Sanofi in connection with TZIELD, $75 million from Gilead and $45 million from Incyte in connection with ZYNYZ,
Okay. Onto our pipeline over a minimum that dual Karmazin revolver due ORADC. designed to deliver DNA alkylating to Akamai's and cytotoxic payload to tumors expressing B7-H3. B7-h3 is a member of the B7 family of molecules involved in immune regulation, but we do always designed to take advantage of this antigens, 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 overdue oh 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 receive vobra 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 androgen 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 vobra duo on 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 ASH, so 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. This 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 or durvalumab our bispecific tetravalent PD-1 by CTLA-4 DART molecule. We designed large AlloMap 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 large HEAT study, a randomized Phase 2 clinical trial of lower general and that 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 two to one 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 larger AlloMap 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 NGDL. 24 is our next-generation bispecific CD123 by CD3 DART molecule that incorporates a CD3 component designed to minimize cytokine release syndrome while maintaining an antitumor cytolytic activity and permitting intermittent dosing through a longer half-life our Phase one dose escalation study of MGDO. 24 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 MGTO. 24 at predefined decision points during the Phase one 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 license from synergy effects. The first of these is MDCO. 26, a clinical ADC, incorporating a B7-H3 targeting antibody and a novel topoisomerase one inhibitor based linker payload since Pecan Acres is cleavable, linker payload is based on equity, can a clinically validated and potent cancer seeking that readily combines with Zinifex HyperSpace technology.
We believe Cineplex's approach potentially provides advantages. These are the other topo I summarized one inhibitor based ADCs. In fact, exiting can appears to be more potent and less susceptible to multidrug resistance mechanisms than other checkpoint inhibitors such as SM. 38 and direct city can additionally, site-specific conjugation has been taken to the normally glycosylated amino acid in the Fc domain. Abolish is Fc gamma receptor and mannose receptor binding, which contribute to nontargeted 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 both our dual. We recently initiated a Phase one dose escalation study of MDCO. 26, we view MGCL. 26 as a complementary approach to Barbara Duo for targeting B7-H3. More specifically, we believe that having distinct mechanisms of action will reduce O & M GCO. 26 may address different cancers, tumors 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 fueling our topo one inhibitor strategy as an additional valuable tool in our therapeutic repertoire. We plan to present preclinical data for MGCO. 26 at the upcoming American Association for Cancer Research or AACR annual meeting next month is a preview of what you'll see in preclinical studies MGCO. 26 exhibited a favorable profile with potent in vivo activity to our B7-H3 expressing tumor xenografts, representing a range of cancer indications. MGCL. 26 was tolerated in cynomolgus monkeys, a relevant toxicology model at exposure levels exceeding those required for antitumor activity.
We look forward to showing you the data set next month. In addition we are readying a second topo I summarized one inhibitor based ADCMGCO. 28, for which we currently expect to submit an IND later this year. MDCO. 28 is a preclinical ADC incorporating an ADAM9 targeting antibody and the second of our ADC molecules incorporating Cineplex's novel linker payload ADAM9, or it is integrins and metallic protease Domain nine. He's a member of the A.D.A.M. family of multifunctional Type one transmembrane proteins that play a role in tumor genesis and cancer progression as overexpressed in multiple cancers, making it an attractive target for cancer treatments. MDCO. 28 is a second ADAM9 targeting ADC that we have pursued. First was IMGC. nine 36 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 lead clinical development of IMGC. nine 36. Neither MacroGenics, nor AbbVie intends to further pursue development of IMGC. nine 36 as the molecule did not receive our pre established clinical safety and efficacy benchmarks. We plan to present preclinical MGCO. 28 data at the upcoming AACR Annual Meeting in April as a preview MDCO. 28 exhibited specific dose-dependent in vivo antitumor activity toward ADAM9 positive CDX. and PDX models, including gastric, lung, pancreatic, colorectal and head and neck cancers. MDCO. 28 was well tolerated in a repeat-dose nonhuman primate toxicology study up to 55 milligrams per kilogram. The highest dose level tested of note ocular toxicities that are typically seen with maytansinoid payloads and which we observed in our IMGC. nine 36 cynomolgus toxicology study were not observed in the MGCO. 28 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 MDCO. 28 by the end of 2024. In addition, beyond MGCO. 26 and MDCO. 28, we are exploring additional molecules for potential future IND submission. Stay tuned.
Finally and Noble to XmAb is an Fc optimized monoclonal antibody that targets B. seven H. three, our academic collaborators have initiated an investigator-sponsored, randomized translationally intense phase two investigator-sponsored study of inotuzumab in up to 219 men with prostate cancer. The HEAT study will evaluate the activity of neoadjuvant and inotuzumab 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.
Question and Answer Session
Operator
(Operator Instructions) Jonathan Chang, Leerink Partners.
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 TAM rec 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 have taken an evaluation of our own data that was published recently by Daiichi on the 7,300 molecule it as low this past fall and other data that was out there with regard to activity against the prostate cancer. And with that, as I have noted, and which we have not changed of the ranges that we were seeing. Just to recall, we saw about half the patients and our 3 mg per kg of Q3 weekly dosing as Alberto in our expanded approximately 40 patient cohort of about half those patients reducing PSA 50 from baseline.
And given the dosings right now of 2.7 Q4 into 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 mix Q4 as compared to historical treatment with a three mix Q3. As a result, we expect the PSA 50 to be in a similar range, somewhere between 40% and 60%, PSA 50 reduction with regard to overall response rate again, as we had previously presented, approximately a quarter of patients achieved both confirmed and
confirmed responses. And this was similar to that, which was reported by Daiichi up 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. On Slide 8, you reported of 5.3 months of our PFS. And what we have said is that we expect to have at least six or greater in terms of our PFS 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.
Jim Karrels
Understood. Maybe just a clarifying question on on that. So the decision time 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, on given the experience in small cell, for instance, where both Daiichi enhance So 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 on this became a very obvious one to include among among the five, I would say the others were based on our own experiences as well as some preclinical work that we had done against these targets. But again, I am not we are not even limiting it to these five. We are also considering others, which would be very good opportunities for looking at the value of Oprah Duo.
Operator
Kelsey Goodwin with Guggenheim. Your line is now.
Kelsey Goodwin
Okay, guys. Thanks for taking my question. First, regarding that Asco abstract and what should we expect to be included in that? Will it just be safety or well, 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 fall Asco presentation. Thank you.
Scott Koenig
Thank you. So much Kelsey because of the timing, and I'll discuss enrollment in a second, so 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 on safety data and to be included in the abstract, but also noting that our plan was to present, obviously the clinical efficacy 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 have primarily includes the safety data in the abstract.
Kelsey Goodwin
Perfect. Thank you so much.
Operator
Stephen Willey, Stifel.
Stephen Willey
Yes, good afternoon. Thanks for taking the question. Maybe just to 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 had sufficient experience with with that and thanks for the question, Steve.
Scott Koenig
So as we have spoken about it before, on the initial sites with the new amendment that were opened were in the US, 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 create 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 on and don't hold me to the exact number on a proximally a third. The size that we intended to enroll open were never opened 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 we have in Europe and compared to Asia and the U.S., the majority got enrolled in Europe in that and that bolus in the second half of the year.
Stephen Willey
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 all -- again, remember, the regulatory timing for getting on the amendments through was after that of the U.S. So it occurred after U.S. started to enroll these patients. The majority came in in Europe and just 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 Q4 W. doses? I mean, I know you just referenced 2.7 is is it safe to say that you guys have settled on a 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 of final answer on 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 and the expectation, for instance, our PFRPPFS. long occurred to the after the midyear. 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 Danish data safety monitoring committee in January looking at the safety at the time and the activity at the time that was available in January, and we concluded that the both doses should should continue. So I think it will be a decision that we will arrive at by midyear.
Stephen Willey
Okay. And last question is, is the maturity of that RPFS. statistic rate-limiting to your ability then to initiate these additional dose expansion cohorts know that that will not slow that down at all.
Scott Koenig
We are working on both from a regulatory, a regulatory advantage and operationalizing this so that we can get going by midyear.
Operator
Etzer Darout, BMO Capital Markets. Your line is now open.
Etzer Darout
Great. Thanks for taking a question on just a couple for me here to just thinking about on the monotherapy arm for reduced 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, are you sort of maybe changes the dynamic of how you're thinking about pivotal development of overdue?
Scott Koenig
Thanks, Ed. There are again, I won't comment on the activity from the TAMARACK study that will come out at Asco, but obviously, I'm looking at the landscape from 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 on the bill 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 enter into the study with the idea that any Phase three study would likely to be done in a post chemo experience population, we have now changed that view that clearly is in the chemo naive population if both the efficacy and safety warranted. That seems to be a very suitable population, an earlier line 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 will make a make that decision.
Etzer Darout
Thank you.
Operator
Yigal Nochomovitz with Citigroup.
Yigal Nochomovitz
Yes, has gotten in. Thank you. And just to clarify, so for the Asco abstract, it seems like you're just going to maybe focus on the safety. But in the presentation at the conference itself, what should we expect to see any initial radiographic PFS data or not?
Scott Koenig
So thank you very much, Hugo. So I'm clearly we will show as much efficacy data as possible at the cut-off 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 as the end of May, I would presume that there were higher require us to have the material prepared by mid-May. And so my expectation would be that there would be a cutoff date sort of late March or early April.
And with that, we will clearly have a lot of data available on patients that have been on dose for many months. And so that would include obviously, PSA 50 reductions would looked at overall response rates up and have filled a full dataset, obviously, a full dataset with safety. With regard to our PFS, we'll have to see how many patients and have been dosed for how long to see if we can do some at least preliminary cuts on our PFS in 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 the PFS is sort of at least six months, is 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 included there, respectively. And 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 from for TAMARACK?
Scott Koenig
Yes. And again, it will depend on whether we go into the chemo naive population or or chemo experience and how late line we would do those studies. So that's why it's a little broader. If you look at the controls for the studies that you describe on, what obviously will depend on what the controlled drug is. The typical ones, for instance, for the chemo-naive population was docetaxel for around eight months and similarly in the activity for the card study was about eight months.
So yes, I think that again, which population ultimately look at would require more than just six, it would be eight or higher. And certainly, I just don't want to limit what what this drug could potentially treat. We just don't know the answer yet. I would just pointing out the base minimum on particularly on from a later line population, it would be at least six months.
Operator
Jon Miller, Evercore.
Jon Miller
I guess next question, I would love to ask about those additional indications that you're moving over Duo into in the Tamarack study. Do you have any additional data from any of those indications in 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 whitespace there. So can you talk us through a little bit about what changed and why your decision to take it for those indications coming now?
And then secondly, I'd love if you could go in a little bit deeper into differentiation of the new oh two, six B7-H3 ADC from the other topo one payload ADCs against same target that are that are in development and thanks so much, John, yes.
Scott Koenig
So as you well know, while we've been focusing on prostate cancer because of bandwidth, which is correct, as you may recall, that two years ago, we were intending to do an expansion as a further expansion in melanoma, but had to cut back because of cash at that time. So that was that was clearly a population that we had a strong interest. And 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 and with anal cancer with the Volker Duo and small cell was, as obvious, as I alluded to before, are based on others' experience there. So those are the initial reasoning behind going after this. And we believe that with the improved the potential safety profile of the new dosing regimen and these patients with these other cancers will be able to stay on drug longer to have a potentially a good outcome. So that's why we're looking to expand into those indications.
Now with regard to MO. two six, as I pointed out, this is a great opportunity for us to really I've taken it as an important answer, important questions and have 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 Vopak do oil in its activity and what we believe to potentially be a superior topo one inhibitor payload are based on the scientific growth profile.
And as I pointed out from various vantage points, including include increased activity, potency on a less susceptibility to ME. flux of multidrug resistance on 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.
And by the fact that this scientific platform eliminates the binding through Fc receptors as well as mass receptors, one should potentially have the ability to reduce some AILD. effect of with a topo one inhibitor. So from all these vantage point and from all the things that I described earlier, looking at the ability to treat with overdue all looking at potential combinations without 26 down the line looking at treatment of different tumors. I think this provides us with a great opportunity.
Jon Miller
Thanks, Scott. Have we seen all of the data from the various other indications that you were looking at in Phase one before you put those on hold? And if you have not had any announcements of.
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
Kaveri Pohlman with BTIG.
Kaveri Pohlman
Yes, good evening, and thanks for taking my questions for the upcoming readout, you will have overdue data for both docetaxel naive and experienced patients. But since you are not going to have mature rPFS data till second, how are you thinking about making a decision on where to go in terms of a Phase three trial.
Scott Koenig
Another good question because very 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 with 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 and for a moving forward to a Phase three point.
And obviously we don't want to wait till the last minute because operationally, there's a lot to do and not the least of which is engagement with regulatory agencies to describe our 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.
That's helpful. And then maybe my second question is regarding MGDO. two for any color on when you expect to complete the Phase one trial and how much time Gilead will have to make a decision to opt in once you provide the data.
So with regard to oh two four, as I was commenting on, we are in the middle of dose escalation, as you know, for on 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's the most of the limiting factor here.
So I can't tell you what the end will be. We are through many cohorts of groups and continuing that as quickly as possible. And with that, Juliet hasn't, you know, until a short period of time after we present the full Phase one data to them to opt-in on the program. So the clearly there's still time and clearly it's a firm. And during the dose escalation, if they decide they want them opt-in, they have the right to do so.
Operator
Tara Bancroft, TD Cowen.
Tara Bancroft
Hi, good afternoon. So I understand the rationale for potentially enabling broad development of overdue over the with the inclusion of pre taxane patients on BI. 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. And so we would clearly tried to provide as a detail possible on that population.
Scott Koenig
I don't know how many of the patients. We have that data in the database in terms of the 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.
Tara Bancroft
Okay. Yes, thanks. So and are you're not excluding rapid progressors. Right. And if not, how would you expect then to effect our PFS? Like is that where you're six month versus eight month expectations come from those patients?
Scott Koenig
I know you're I think you've hit the nail on the head, and that's why I'm trying to give a little bit of broad brush strokes on that on understanding of patients, there are rapid progressors are allowed here as we opened up, for instance, the study, the original design of the study required a at least 12 months of treatment on in a rat to be qualified for enrollment in our study.
And when we remove that requirement, clearly of patients who had very short courses in and some progress quickly as well, it is very newly diagnosed have patients on arm before they got their initial treatments 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 a tail wells that I'm having a baseline of six months is not unreasonable for that type patients.
Tara Bancroft
Okay. Thank you so much.
Operator
Peter Lawson, Barclays.
Peter Lawson
Hey, this is Peter Lawson. I'm from Barclays. Couple of questions. Firstly, in the abstract where we see safety this broken out by discontinuation rate and also side effects such as Hand-foot perfusion, and then I've got a follow up.
Scott Koenig
Peter you will have the discontinuation rate as of the cutoff of January data. With regard on 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.
Peter Lawson
Good, thank you. And then the Tamarack City have patients been exposed to radiopharmaceuticals such as Victor will you be able to break that out eventually?
Scott Koenig
Yes, unfortunately on 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 from the actual availability of predict, though, and the timing didn't work out to get those at a perfect though progressors and experienced patients there. We expect a few of them from the US, but very small numbers there.
Peter Lawson
And then just a quick question for Jim on the puts and takes around that around the cash guidance just with the expansion, the B. seven H. three clinical trials kind of I guess that's it negative for cash. But what are the puts and takes we should kind of be thinking about for you to maintain that cash guidance?
Jim Karrels
Thanks, Peter. Thanks for the question. So our guidance of cash runway into 2026 reflects the additional cohorts under the TAMARACK umbrella additional do our cohorts. So everything we're talking about all of these studies that we're currently of running and talking about running are included as part of our guidance.
Peter Lawson
But are there any additional inflows of cash you're thinking through Tekelec counterbalanced, though, that was that always in the cash guidance?
Jim Karrels
I'm Peter, I'm sorry. Could you repeat the question, please?
Scott Koenig
Or is there any additional cash inflows that you're thinking through all those cohort always in the cash guidance?
Jim Karrels
Those cohorts are new to the guidance. There have been some savings on where there's always the possibility of additional business development activities. And of course, with a $1 billion milestones hanging out there related to both teams, yield and designers, of which we've handicapped significantly, we would anticipate a recognition of some of those over the over the next couple of years and we had elsewhere and there were some additional revenues coming in that weren't anticipated originally that are part of this guidance.
Peter Lawson
Okay, thank you so much.
Operator
Silvan Tuerkcan, Citizens' GMP.
Silvan Tuerkcan
Thank you, and thanks for taking my question and congrats on the progress and maybe piggybacking a little bit on a previous question. What's the bar for the safety profile in the abstract or offer at the ASH presentation versus the safety profile that we've seen on the older doses. And I'm asking in particular, maybe on the grade three or higher issues that we've seen with the hand for them and some signal and perhaps neutropenia, 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, Sylvan, I just wanted to correct you. Our concern was not Grade three Hand-foot obviously, we want to avoid that. And although the incidence of that was quite low on the issue was that patients would either Grade one grade two 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 news is that we can decrease the incidence totally.
And then for those that have with a reduced incidence of converting or preventing them from going from Grade one grade two would be on what our goal is there with regard to the neutropenia. And clearly that is something most likely due to freed up THOMPSON getting to the bone marrow. But again, this is this is a situation where and it was largely a laboratory value. It did not result in increased infections or febrile neutropenia and so on. This is mostly handled by and holding that holding the drug. We're 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 as concerning to the treating physicians in managing these patients.
Silvan Tuerkcan
Great, thank you. And maybe about the LoRa kit 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 and look at them?
Scott Koenig
With regard to the timing of this, we'll provide, as I said earlier, update on this study, it ultimately will depend on the speed in which we can enroll these patients clearly over the next two months will be only exceed on the plan or will it take longer, meaning later in the year to get full enrollment of this study. If it's the latter, it's more likely we'll have a more fulsome update in early 25. But then again, we'll be able to give you a little bit more guidance later in the year based on enrollment rates.
And with regard to one of the as a success in this trial. Clearly, we're testing this in the chemo naive population in combination with docetaxel. And I think that if that trial is successful, it's a great problem to have if the vulvar dual pans out also in that same line of therapy. And I should also say that we are not eliminating the possibility that we're going to look at LoRa key answers or general I-Mab in later-line prostate cancer. That is certainly a possibility to consider. But as I said before, we are also going to look to larger format outside of prostate cancer going forward. So it's just too early to make a decision on registration studies until we have the data, I think.
Operator
(Operator Instructions) Yigal Nochomovitz with Citigroup.
Yigal Nochomovitz
Yes, hi. Thank you so much for taking the follow-up. Scott, I just had a quick follow-up on TAMARACK. I know it's unusual that you see a trial, but 77% overenrolled relative to the target and enrolled very quickly. Can you just comment on some of the factors that resulted in the heavy over enrollment and as well, the or the speed to which it was overenrolled.
Scott Koenig
Yes. So on the go with regard to our decision on leading so many more patients into this study, we felt it was not ethical and for us to not allow these patients into the study if they had already been in screening and past 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 on, you know, the surge of enrollment once we had the go-ahead from the amended protocol in Europe, and there was tremendous enthusiasm to join the study. And I'm sure there are a lot of different reasons. I as I was pointing out, some of the amendments included the fact that we didn't require 12 months of treatment on an interest.
And so patients who were progressing on 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 are 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.
Yigal Nochomovitz
Got it. Thank you very much.
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 the Asco in the near term and talk to you at future times that 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.
