Good afternoon. We will begin the MacroGenics 2023 second quarter corporate progress and financial results conference call in just a moment. All participants are in 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 MacroGenics conference call to discuss our second quarter 2023 financial and operational results. For anyone who's not had the chance to review these results, we issued a press release this afternoon outlining today's announcements, which is available under the Investors tab on our website at macrogenics.com. You may also listen to this conference call via webcast on our website, where it will be archived for 30 days, beginning approximately two hours after the call is completed. I would like to alert listeners that today's discussion will include statements about the company's future expectations, plans, and prospects that constitute forward-looking statements for purposes of the Safe Harbor provision under the Private Securities Litigation Reform Act of 1995.
Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in the Risk Factors section of our annual, quarterly, and current reports filed with the SEC. In addition, any forward-looking statements represent our views only as of today and should not be relied upon as representing our views as of any subsequent date. While we may elect to update these forward-looking statements at some point in the future, we specifically disclaim any obligation to do so, even if our views change, except to the extent required by applicable law. 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. This afternoon, I will provide key updates on our clinical programs. 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 quarter ended June 30, 2023, which highlight our financial position. As described in our release this afternoon, MacroGenics' total revenue was $13.1 million for the quarter ended June 30, 2023, compared to total revenue of $26 million for the quarter ended June 30, 2022. Revenue for the quarter ended June 30, 2023, included recognition of $1.6 million in contract manufacturing revenue and Margenza net sales of $5.1 million, compared to net sales of $4.7 million for the quarter ended June 30, 2022. Our research and development expenses were $43.2 million for the quarter ended June 30, 2023, compared to $51.7 million for the quarter ended June 30, 2022.
The decrease was primarily due to decreased costs related to discontinued studies, partially offset by increased expenses related to preclinical antibody drug conjugate, or ADC, molecules, and increased clinical expenses related to lorigerlimab and vobra duo. Our selling, general, and administrative expenses were $13.7 million for each of the quarters ended June 30, 2023 and 2022. You'll notice approximately $100 million as a component of other income on our income statement. Let me take a moment to explain. Under GAAP guidelines and pursuant to FASB's ASC 470, in March 2023, we recorded the $100 million proceeds received from the sale of our royalty interest on global net sales of TZIELD to DRI Healthcare Acquisitions, LP, or DRI, as a, quote, liability related to future royalties, unquote.
This liability was to be amortized over the term of the arrangement using the effective interest rate method. Sanofi subsequently acquired both Provention Bio and the TZIELD royalty interest in milestone obligations from DRI in April 27, 2023, obviating the need for MacroGenics' involvement in the transfer of royalty payments to DRI. This resulted in a change to the arrangement, which was evaluated as a modification under the provisions of ASC 470. Accordingly, we recognized approximately $100 million as a component of other income on our financial statements for the quarter ended June 30, 2023. Our net income was $57.5 million for the quarter ended June 30, 2023, compared to a net loss of $41.3 million for the quarter ended June 30, 2022.
Our cash, cash equivalents, and marketable securities balance as of June 30, 2023, was $240.3 million, compared to $154.3 million as of December 31, 2022. Our cash balance as of June 30, 2023, did not include a $50 million milestone payment from Sanofi subsequently earned. Payment of this milestone was triggered pursuant to Sanofi's July 28 announcement that the PROTECT placebo-controlled study investigating TZIELD, or teplizumab, in patients with newly diagnosed stage three Type 1 diabetes, met its primary endpoint, having demonstrated preservation of beta cell function. This milestone was part of the March 2023 agreement originally between MacroGenics and DRI, the royalty interest and milestone payment obligations of which were sold by DRI to a subsidiary of Sanofi in April 2023.
Finally, in terms of our cash runway, we anticipate that our cash, cash equivalents, and marketable securities balance of $240.3 million as of June 30, 2023, the $50 million milestone subsequently earned, in addition to projected and anticipated future payments from partners and product revenues, should extend our cash runway into 2026. Our anticipated funding requirements reflect expected expenditures related to the Phase 2 TAMARACK clinical trial, the Phase 2 study of lorigerlimab in metastatic castration-resistant prostate cancer, as well as our other clinical and preclinical studies currently ongoing. 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, and I will walk you through each of our key programs momentarily, as well as tell you about our plans for upcoming clinical programs. Before I do that, I'll quickly remind you that over the past year, through our business development efforts as well as milestone achievement, we have generated $320 million of non-dilutive capital. 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 is designed to take advantage of this antigen's broad expression across multiple solid tumor types. We began enrolling the TAMARACK Phase 2 study of vobra duo in patients with metastatic castration-resistant prostate cancer under a modified study protocol during the second quarter.
You may recall that we made this modification to address the changing treatment landscape for patients with mCRPC, and enrollment has been proceeding nicely. We hope to enroll a majority of the 100 patients across the 2 experimental arms of 2 mg per kg or 2.7 mg per kg every 4 weeks in 2023 and provide a clinical update in 2024. I'll update you on lorigerlimab, our bispecific tetravalent PD-1 by CTLA-4 DAR 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. You may recall that we presented encouraging preliminary clinical results from a single-arm dose expansion study of lorigerlimab in patients with advanced solid tumors in a poster session at the ASCO Genitourinary Cancers Symposium in February 2023.
Based on the strength of the mCRPC data presented, we plan to commence enrollment of a randomized phase 2 study of lorigerlimab in combination with docetaxel versus docetaxel alone in second-line chemotherapy, naive mCRPC patients in the coming weeks. A total of 150 patients are planned to be treated in the 2 to 1 randomized study. The current study design includes a primary study endpoint of radiographic progression-free survival. In addition, we continue to enroll patients in the phase 1 dose-escalation study of vobra duo in combination with lorigerlimab in patients with advanced solid tumors, including renal cell carcinoma, pancreatic cancer, ovarian cancer, hepatocellular carcinoma, mCRPC, and melanoma. We anticipate commencing the dose expansion portion of the study by year-end, 2023.
Next up, MGD024 is our next-generation bispecific CD123 by CD3 DAR molecule that incorporates a CD3 component designed to minimize cytokine release syndrome while maintaining antitumor cytolytic activity and permitting intermittent dosing through a longer half-life. Our phase I 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 I study. Finally, enoblutuzumab is an Fc-optimized monoclonal antibody that targets B7-H3. Based on the recently published results from a phase II investigator-sponsored study of enoblutuzumab in men with prostate cancer, MacroGenics and collaborators at multiple academic institutions plan to initiate an investigator-sponsored, randomized, translationally intense neoadjuvant prostate cancer study in high-risk population by early 2024. Now I'd like to give you some perspective on where MacroGenics intends to advance.
I'll remind you that over our history, we have maintained our focus in developing innovative antibody-based therapeutics, having had a role in the development of three products now approved by the U.S. FDA: Margenza, TZIELD, and Zynyz. More recently, as an extension of this emphasis, we've accelerated our ADC efforts. This has been possible through the following. First, our technology-enabling partnerships, most notably our two collaborations with Synaffix, which has recently been purchased by Lonza. We have reviewed multiple linker payload technologies and are pursuing Synaffix' approach, which utilizes various linker toxins conjugated to a site-specific glycan within the Fc domain of antibodies. This affords us the ability to exploit different cytotoxic mechanisms, including topoisomerase inhibition, microtubule inhibition, and DNA damage in up to seven ADC molecules incorporating Synaffix' technology.
The second element we believe allows us to extend our reach into ADCs is leveraging our 20-plus-year history of pursuing first-in-class target discovery, in addition to our antibody engineering expertise. Finally, the third element is our proven ability to develop product candidates through FDA approval, coupled with our commercial scale manufacturing and external supply chain management capabilities. We are very excited about where this could take us in developing ADCs to treat cancer. As previously indicated, we intend to submit an investigational new drug or IND application to the U.S. FDA by the end of this year for the first of potentially multiple new ADC molecules, which incorporate a topoisomerase inhibitor payload.
To conclude, we believe we have the technical development and clinical expertise, and even the necessary financial resources to support execution on our plan of developing and delivering life-changing medicines to cancer patients in 2023 and beyond. We would now be happy to open the call for questions. Operator?
Thank you. If you would like to ask a question, please press star one, one. If your question has been answered and you'd like to remove yourself from the queue, please press star one one again. Our first question comes from Jonathan Chang with Leerink Partners. Your line is open.
Hi, guys. Thanks for taking my questions. First question, can you give us a sense of how enrollment in the Phase 2 TAMARACK study has progressed? Just trying to get a sense of when in 2024 we might see data.
Thank you, Jonathan. I'm very encouraged by the rapidity of enrollment at this point now, as many of the sites have incorporated the amendments to the protocol. We still have additional site initiation visits to complete on additional sites. Based on what we've been seeing, in this group of sites, I stick with what I have said, that the majority of patients should be enrolled in the study this year, and we should complete it in the first part of 2024.
Got it. Thank you. 2nd question: What do you need to see from the, either of the Phase 2 prostate cancer studies, to support advancing these programs into the next stage of development?
With regard to Tamarack, as you know, we had seen a very encouraging data with regard to late-stage mCRPC patients, with regard to PSA50 reductions, as well as objective responses. The goal of this study, in fact, is to achieve responses in terms of efficacy that were similar to that observed at the doses that we had treated before, as you recall, 3 mg/kg on a Q3W basis, but which most of those patients had dose reductions during those course. What is more important, at this point, is to see some improvement in the side effect profile. In particular, well, the most disconcerting side effect was hand-foot syndrome in these patients who developed Grade 2 with pain.
We would like to see a reduction, obviously, in, in that grade and obviously the incidence as well. With regard to the efficacy parameters, again, just to refresh everybody's memory, we saw approximately half those patients have PSA50 reductions. Of course, we would like to see in the order of around 40%-60% or even better, obviously, if that is achievable, in that population with concomitant tumor control and continued treatment. With regard to the lorigerlimab study, in terms of outcomes, obviously, we were looking for an acceptable safety profile.
In terms of efficacy, if you look at the historical data in terms of control groups, which we obviously include here, of patients treating with docetaxel, historical data says an RPFS of 8 months, is what you would like to exceed. We'll have to see, if we're able to achieve that, by certainly several months.
Got it. Thanks for taking the questions.
Thank you. Our next question comes from Peter Lawson with Barclays. Your line is open.
Thanks, Scott. I guess initially, just as a follow-up to Jonathan's question, the data that we could see for your B7-H3 for the phase III-s orry, the phase 2 data, can we see that in the second half of 2024? For the phase 1 combination data, is that something like a first half 2024 data set go?
Peter, as things go now, as I said to Jonathan, and the encouragement about where we are enrolling, if this continues at this pace, I think the second half 2024 presentation of, of, of data is certainly possible for the TAMARACK study. Obviously, we'll have to monitor that the rest of the year in terms of enrollment. I should also point out that this is an open study, so we will take interim looks at that data along the way and, and may be able to come to some conclusions earlier before we even have the full body of data from that study. Again, I would be consistent with targeting the second half of the year and, you know, at this point.
With regard to the combination study, as we pointed out, we're sort of trying to fine-tune the combination of vobra duo with lorigerlimab right now, individually in combination. Once we settle on what that dose to use, the doses to use moving forward in combination in expansion studies, we expect that to occur by the end of the year. Again, could it be the first half of the year? Possible. Right now, let me bring you up to date. Once we have picked that, those doses and started those expansions, I'll be able to give you a little bit more definition when that will happen.
Gotcha. Thank you. On ADAM9-
Yeah.
I know there's an update this year. Kind of, what kind of update would that be? Will we see data or is it kind of a go, no-go decision? Will the data involve the, the lung cancer data set?
You know, as you know, we've discussed this before, ImmunoGen is conducting the clinical studies. They're following through on the patients with lung cancer to identify an appropriate dose, making decisions about go forward. We have not discussed with them the specifics about what would be discussed and, and presented. We should be doing that soon. Again, updates later this year. The nature of what will be contained, I don't have an answer to you at this time.
Great. Okay. Thanks so much, Scott.
Thank you. Our next question comes from Charles Xu with Guggenheim. Your line is open.
Hi, guys. This is Rosie on for Charles Xu. Thanks for taking our questions. First question is, with regard to the changing landscape in mCRPC, how are you changing or setting expectations with regards to the development positioning of vobra duo and lorigerlimab next to something like Pluvicto?
If I understand your question, how are we anticipating the use of these drugs in face of where Pluvicto is at this point and in the future? Is that, is that correct?
Yes.
Okay. You know, clearly, Pluvicto is, is, is, has changed the landscape for treatment. It is being, used, currently right now in major medical centers that have, PET scanning capabilities, for PSMA. There has been, as you know, some limitation in its, distribution in terms of supply, which is, being addressed by Novartis. There will be increased use, with time. I, I think at, at this point, we'll, you know, we have to wait, to see the data on, the results of Pluvicto, in earlier lines of therapy. You know, right now it's more in a later line of therapy.
When we have completed our study results, we will e-evaluate what, where the appropriate line of therapy will be in which populations, but it, right now, it's just too early. Also mechanistically, we're talking about completely different mechanisms, and also the toxicity profiles are quite different. I think that this is an opportunity where different mechanisms of action give greater number of choices for treating physicians and their patients. I think it's a, it's a good story for patients, that new modalities will be available very soon.
Thank you. If I can ask a second one real quick, this one's regarding the vobra duo combo. Are there specific histologies that you potentially wanna focus on for the dose expansion?
Well, as we've pointed out, in today's call and, and previously, we are looking at 6 different solid tumor types right now. We have not selected which ones to do yet for the expansion. Certainly, prostate, prostate cancer will be one of them, but which additional others we will select, we have yet to make that decision. We'll, again, in the near term, we'll be able to, to provide that information.
Thank you. Our next question comes from Etzer Darout with BMO Capital Markets. Your line is open.
Great. Thanks for taking the question. The first one, just wondered if you plan to disclose any of the data from the dose escalations of vobra duo plus for lorigerlimab prior to moving into expansion studies? Secondly, if you maybe could comment on the progress of any of the kind of other tumor types, lori, sort of monotherapy, maybe any progress there with other tumor types, when we could get an update there, or any other tumor types that you would look to explore with lori, either monotherapy or combinations? Thank you.
Etzer, we'll have to, again, as you know, as I had said just earlier today, you know, we're honing in on the specific doses for the individual components of the vobra duo combo. Ultimately, it'll be determined of how many patients we have available at that time, to assess. My, my inclination right now is to start and move forward in expansions in particular types, which I alluded to before, prostate and probably one or two others. And probably at that time, once we have that data, we would be in, I think, a better position to present the, the, the total data. But again, this is subject to further discussions later this year.
With regard to other tumor types of lori, besides the data we presented at ASCO GU, as you know, we have previously said that we've had objective responses in three other cohorts that we were testing, including MS-stable colorectal cancer, melan- melanoma and lung cancer. What I've also indicated on previous calls is that for us to move forward into a more wholesome phase 2 study, I'd like to see some additional patients being treated as monotherapy, to give to, to better determine the activity in particular tumors. I, I pointed out, for example, in the lung cancer cohort that we had, we lost a lot of that data because of, of, of patients that were treated in Ukraine.
For the case of the MS-stable colorectal cancer patients, I pointed out we had very few patients with without liver metastasis, which has been an area being pursued by others. I'd like to see additional patients being treated as monotherapy before making the decisions going forward. The melanoma data, we're very encouraged by. As you know, historically, we've had we have noted that we've had very significant responses in, in, with vobiduo and melanoma as well. That is one of the tumor types we're potentially enrolling in the combination study going forward, so.
Great. Thank you.
Thank you. Our next question comes from Kaveri Pohlman with BTIG. Your line is open.
Yeah, good evening. Thank you. Thanks for the updates and for taking my questions. Sorry if I missed this, but for lorigerlimab and docetaxel combination study, it's a randomized trial for 150 patients. Can you give us a sense on how long it will take to enroll the study and to get RPFS? Also, do you think that you can just expand it to a phase 3 trial if the interim data looks good? Just wanna know how you're thinking about it.
Yes, Kaveri, thank you very much. So we're, we're very close to you know, enrolling the first patients. We've initiated sites. Patients are being screened now, the startup of this trial. Right now, you know, until you start enrolling, you won't know the, the, the rate of enrollment, but right now, the anticipation will take us through this year and through a good part of 2024. So I, at this point, it'll be just too early to predict when we'd be able to do the readout at the study. You know, most likely in early 2025, but that's all conjecture at this point.
Got it. That's very helpful. Then for MGD024, can you tell us how is the enrollment going? Any feedback you have received from the physicians so far, can you accelerate dosing based on your previous clinical experience with flotetuzumab hair?
As, as you know, in, in irrespective of, of what the product is, any CD3-based bispecific molecule, when interacting with the regulatory agencies, there is a lot of prudence in terms of the dose escalation speed on which these things can be conducted, despite the fact that we had very significant data showing dramatic reductions in cytokine production in primate model systems, and anticipate that we could move this faster. Having said that, we are following what was discussed with the FDA. We are right in the middle of a dose escalation. The study is going well, and that's all I can say at this point.
My sense is, is that once the dose has been picked, from that dose escalation and we go into a, a more phase II like, study, there may be greater opportunities to accelerate the, the development. Again, that will be with, either with Gilead, if they opt into the program after the phase I or during phase I, or by ourselves if, if it warrants it. Still too early to tell.
Makes sense. Thank you.
Thank you. Our next question comes from Yigal Nochomovitz with Citigroup. Your line is open.
Hi, Scott. Thanks for taking the question. On the, on the TAMARACK study in metastatic CRPC, and then the, the phase I/II dose escalation with the, with the combo, and I think you mentioned CRPC there as well, and you want to do an expansion. Can you just comment, are those patients, those prostate patients, are relatively similar in their degree of pretreatment? You mentioned advanced solid tumors for CRPC, I still wasn't clear if it was similar or if the ones in the phase I/II were more significantly pretreated versus TAMARACK. Thanks.
There are some slight differences in, in eligibility. We have a little bit wider in TAMARACK, but the majority of the patients will be quite similar. You know, we obviously wanted to compare apples to apples with the modification of dose. We obviously wanted to get this enrolled quickly, so there was some minor changes, but I would say they'll be very easily comparable to the previous data. Then same story with the combo for whatever prostate patients come in, very late stage patients as well, typically have advanced on androgen receptor targeting agents on, on taxane and often experimental agents as well.
Okay.
We think the data set will be, we will be able to compare, each one, so.
The, the reason I ask is 'cause, I mean, if you do the prostate expansion in the Phase I/II with, with the vobra and the larotrectinib, and that looks really good, I'm just curious how you're thinking about a pivotal study and, and how you would register the, the product, because whether you'd, you'd, you'd want to register with, with the monotherapy, with vobra duo, or if the larotrectinib vobra duo looks really good in prostate, if that would be the way to go forward, to, to, to take the drug to market, the, the combo to market. That's more of a strategic, strategic question, but just curious, how you're thinking about that.
Yeah, you know, obviously this is constant discussion. Obviously, we, you know, with the data on the larotrectinib mono story, being so encouraging, we decided to move a little bit upline with now going into chemo-naïve patients, but with androgen receptor-experienced patients. That, you know, right now there is no other checkpoint that is vying for that population, so this is a great opportunity where we can demonstrate in that line of therapy success. With regard to the vobra story, either as monotherapy or potentially combination with lori, that's a nice problem to have, if both look very successful, both the results from TAMARACK and then the combo. We'll address that as the data comes out next year.
Thank you. Our next question comes from Stephen Willey with Stifel. Your line is open.
Yeah, good afternoon. Thanks for taking the questions. I guess now that you've removed the control arm from TAMARACK, I'm guessing there's gonna be more of an emphasis on response rate versus, I guess, any kind of event-driven efficacy data. I guess I'm just curious, based upon the eligibility criteria of TAMARACK, you know, what percentage of patients you're expecting to actually have soft tissue disease that is resist valuable?
With that-- from that parameter, I think, our experience in, in many of the, in the trials to date, have at least half those patients, and I would not be surprised, given this is an international study, based on actually the results from the LORI trial that we presented, almost all, the majority of those patients had visceral involvement. It was not only bony involvement. I, I'm, I'm not at this point, I am not concerned that we will be seeing a tissue-limited population. I think there'll be enough data to that. Clearly, we'll, we'll monitor that going forward, and we certainly can add more patients if necessary, but I don't think that's gonna be a problem.
Okay. I guess just a question on vobra duo. You've pressed the pause button here on single agent dose expansion in other tumor types.
Yeah.
I think that's, despite some of the early signs of efficacy that you talked about earlier, are you thinking of reinitiating any of those development efforts again, once you get confirmation on dosing and scheduling from TAMARACK? Or does this next Gen ADC effort now kind of get prioritized in front of, in front of vobra duo?
Yeah, I mean, my answer to you is, is we certainly are interested, given the broad expression of B7-H3, across, you know, a large number of solid tumors and our experience with them, that additional tumor types will be pursued. Clearly, we would like to see, with vobra duo, you know, the, that improvement in safety, which I discussed earlier. And, you know, one and I mean, I can guess that at this point, or we could, you know, forge ahead and, and just move that, but I think it's, it's more prudent, given, as I said earlier today, that enrollment is going well, and we'll have the answer soon, to initiate other types at that, at that point.
We feel very strongly that we are building a great opportunity and franchise within prostate cancer, you know, with the LORI, with vobra duo, the potential combination. Then, as we said today, the plans to start a with academic collaborators, a neoadjuvant study with enoblituzumab, in prostate cancer. We're trying to really cover the entire landscape for treatment of patients with prostate, but that does not interfere with our enthusiasm for pursuing this in other tumors as well.
All right. Thanks for taking the questions.
Thank you. Our next question comes from Jonathan Miller with Evercore ISI. Your line is open.
Hi, guys. Yeah, thanks for taking the question. I would look to ask more about the financials and the runway guidance. So obviously, you mentioned that covers TAMARACK and LORI phase 2 and ongoing trials. How much does that cover of a new ADC? How much does that cover for trials that aren't currently running or anticipated to start? And does that count any new indications, either for vobra duo or for LORI and expansion?
Yeah. Thanks, Jon. Very good question. Obviously, with today's announcement, we're very excited about getting that additional $50 million milestone from achieving it through, you know, the results of the PROTECT study. So obviously, just again, to put it in context, as we said earlier, with the $320 million in the passing of non-dilutive capital, the likelihood of additional milestones goes up because of the hitting the primary endpoint. Of course, it's dependent on the opportunity to get TZIELD approved in the new indication as well as different regions for the original indication that has been already approved in the U.S. FDA.
That increases likelihood there, which means a potential increased opportunities for more milestones and as well as royalties. I should also point out that Incyte announced last week that they completed enrollment in the two registration studies for the anti-PD-1 Zynyz in lung cancer and anal cancer. Again, with those readouts as results accrue, if those are successful, what we have on the table are a potential $320 million of regulatory clinical milestones, another $330 million in commercial, so over $600 million there, and we still have the potential for another $380 million from Sanofi. That's over $1 billion of potential milestones from two approved products.
Getting back to the essence of your question, just with this additional 50 and the studies ongoing, that does include the new antibody drug conjugate that we will file an IND the fourth quarter this year. It does include the opportunity to do additional studies, whether it be for new tumor indications, or additional studies in different lines of prostate cancer. Those are under discussion right now, and it doesn't take away from any of the work preclinically for a second ADC from the Synaffix that we said is ongoing right now, which we're hoping to target for an IND in 2024, plus a lot of other preclinical development activity that we have not discussed to date.
We're very, very, very encouraged, both with our cash runway and the opportunity to pursue a very clinical and preclinical pipeline.
Great. That makes sense. I guess, I know you sometimes include risk-adjusted future milestones in your cash runway. Can you talk a little bit about how much of that potential $1 billion in milestones you're counting on when you give that runway into 2026?
Yeah, we haven't broken that down. Clearly, we make those adjustments based on, on real time results, and certainly, we have the opportunity to adjust up a probability based on the fact that Sanofi has said that they are going for regulatory approval. Obviously, we'd like to see the data. We have not seen the data on the results of the new study. At this point, we're not in a position to break out the specifics there.
I would just... This is Jim, Jonathan. I would just add to that, that historically, if we look back at the probabilities that we use for risk adjustment, we've been very conservative.
Okay, makes sense. Thanks so much.
Thank you.
Thank you. Our next question comes from Silvan Tuerkcan with JMP Securities. Your line is open.
Yeah. Hi, thanks for taking my question. A couple of questions on TAMARACK here. The patients group that you're expecting to enroll by the end of the year or maybe early next year, will that have sufficient chemo-naive patients, that could be also an option, you know, you know, maybe better than the chemo-experienced patient for a registrational study? Or, what are your options after, you know, in terms of patient populations that you have in this Phase 2 to go on?
No. Well, Silvan, no, actually, that is one of the several hard, fast enrollment criteria. They have to have been exposed to a chemotherapeutic, most likely, docetaxel. In this particular study, we want to really compare the results, as I described earlier, of our previous experiences with vobra duo in a later-line population that is chemo-experienced. Not in this study. We are certainly interested in looking at opportunities in earlier lines of therapy, including hormone-sensitive populations, but nothing is on the table right now.
Great. Thanks. That's very helpful. Then, at ASCO, w e saw first, in human data from Hansoh's ADC, also directed B7-H3. Are there any learnings from that that we can apply to vobra duo?
Yeah. I mean, I would say the most encouraging data was obviously a small data set, and they were talking about expansion in other tumor types, is that of the 9 patients with small cell lung cancer, 7 had an objective responses, which fits the data that Daiichi Sankyo has discussed also in the small cell population. So clearly, this is a histological type that we are certainly considering adding to the types being tested. We, as you may recall, we have only had one patient with small cell cancer in our dose escalation, who actually did very well on vobra duo at a lower dose.
That patient was on treatment for over 6 months, with tumor shrinkage, didn't have an objective response, but really responded well to the therapy. Clearly, that opens up for us, you know, a confirmation that a small cell may be an indication we should also pursue.
Great. Well, thanks. Thanks for taking my questions.
Thank you.
Thank you. Our next question comes from Boris Peaker with TD Cowen. Your line is open.
Hi, my name is Hangfei Fu for Boris Peaker. I would like to ask, how confident, for Vobra Duo, how confident are you that the 2 doses that you're testing will give you the ideal dose moving forward? And you think, about the registrational trial, do you expect further dose modification is needed? Thank you.
As any experiment being conducted, you go with the data you have, and you have a hypothesis, and, you know, we feel that the doses we selected were the right ones. This was based on a full analysis of the data in all the expansion cohorts with regard to side effect profiles, tumor responses, pharmacokinetics. We tried to bookend based on what the, the real exposure was in patients. As I commented on earlier, the majority of patients had dose reductions, so we feel that we've picked the two doses that should give us more clarity with regard to an improved safety profile and activity profile. As much as that can guide us, you know, we're hoping that that was the right, the right selection and the right answer.
If we have to make modifications, in some way subsequently, once we get the data, you know, we'll do it if the drug looks both active as well as relatively safe.
Got it. Thank you for taking my question.
Thank you. As a reminder, if you'd like to ask a question, please press star one, one. There are no further questions. I'd like to turn the call back over to Dr. Koenig for closing remarks.
Well, thank you very much, operator, and thank you everyone for participating in our call today. We look forward to providing further updates both on our clinical and preclinical pipeline in the coming months. Have a good day.
Thank you for your participation. This does conclude the program, and you may now disconnect. Everyone, enjoy the rest of your day.