MacroGenics Q4 2023 Earnings Call Transcript

Quartr
Provided by Quartr
March 7, 2024

There are 12 speakers on the call.

Operator

Good afternoon. We will begin the MacroGenics 2023 4th 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 Carrolls, Senior Vice President, Chief Financial Officer of MacroGenics.

Speaker 1

Thank you, operator. Good afternoon, and welcome to MacroGenics' conference call to discuss our Q4 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.

Speaker 1

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 this 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 Doctor.

Speaker 1

Scott Koenig, President and Chief Executive Officer of MacroGenics.

Speaker 2

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.

Speaker 1

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 $58,700,000 for the year ended December 31, 2023, compared to total revenue of $151,900,000 for the year ended December 31, 2022. Revenue for the year ended December 31, 2023 included $29,000,000 in revenue from collaborative and other agreements, Margenza net sales of $17,900,000 $9,800,000 in contract manufacturing revenue. Our research and development expenses were $166,600,000 for the year ended December 30 1, 2023 compared to $207,000,000 for the year ended December 31, 2022.

Speaker 1

This decrease was primarily due to decreased manufacturing related costs for VOBRID DUO, decreased development in clinical trial costs related to margetuximab and decreased costs related to discontinued studies, partially offset by increased expenses related to MGC-twenty six and MGC-twenty eight development. Scott will tell you about these 2 ADC product candidates in a few minutes. Our selling, general and administrative expenses were $52,200,000 for the year ended December 31, 2023, compared to $58,900,000 for the year ended December 31, 2022. The decrease was primarily related to decreased selling costs for Margenca. During the year ended December 31, 2023, MacroGenics received $100,000,000 proceeds from the sale of our single digit royalty interest on global net sales of TZYLD to DRI Healthcare Acquisitions LP in March.

Speaker 1

In addition, we received a $50,000,000 milestone payment from Sanofi related to the achievement of a primary endpoint in a tZILT clinical study. Under GAAP guidelines and pursuant to financial accounting standard for accounting standards calcification or ASC 4 70, This combined $150,000,000 was included in other income as a gain on royalty monetization arrangement in 2023. Our net loss was $9,100,000 for the year ended December 31, 2023 compared to a net loss of 100 and $19,800,000 for the year ended December 31, 2022. Our cash, cash equivalents and marketable securities balance as of December 31, 2023 was $229,800,000 compared to $154,300,000 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 $229,800,000 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.

Speaker 1

Our anticipated funding requirements reflect expected expenditures related to the Phase 2 Tamarac clinical trial, the Phase 2 lORIKET study of lorazirlimab in mCRPC as well as our other ongoing clinical and preclinical studies. And now, I'll turn the call back to Scott.

Speaker 2

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-twenty 22 through our business development efforts as well as milestone achievement, we have received $335,000,000 of non dilutive capital. This includes $215,000,000 from Provention DRI Sanofi in connection with TZeal, $75,000,000 from Gilead and $45,000,000 from Incyte in connection with Zynas.

Speaker 2

Okay, on to our pipeline. Vovarimitimabduacarmizine or vovarduo is our ADC designed to deliver DNA alkylating dura chromycin cytotoxic payload to tumors expressing B7H3. B7H3 is a member of the B7 family of molecules involved in immune regulation. Vobraduo was designed to take advantage of this antigen's broad expression across multiple solid tumor types. As you know, we believe this has the attributes of an ideal cancer target.

Speaker 2

We began enrolling the Tamarac Phase 2 study of OPDUO under a modified study protocol during the Q2 of 2023 and completed enrollment of the study in November, months ahead of the schedule. In fact, 177 patients received VOBRADUO in this study, exceeding the study design goal of 100 participants. As a reminder, Tamarac is being conducted in patients with metastatic castration resistant prostate cancer or mCRPC who were previously treated with 1 prior androgen receptor axis targeted therapy. Participants may have received up to 1 prior taxane taxane containing regimen, but no other chemotherapy agents. This study is being conducted to evaluate vovirdual in patients across 2 experimental arms of either 2 mgs per kg or 2.7 mgs per kg every 4 weeks.

Speaker 2

In January, the Tamarac 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 Q2 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 twenty twenty four. We plan to expand the tumor types being evaluated in the Tamarac 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.

Speaker 2

We expect to initiate dosing in these additional cohorts in mid-twenty 24. Next, I'll update you on loradirlimab, our bispecific tetravalin PD-onexCTLA-four DART molecule. We designed loradirlimab to have preferential blockade on dual PD-one CTLA-four expressing cells such as tumor infiltrating lymphocytes or TILs, which are most abundant in the tumor microenvironment. We are enrolling the lauriquete study, a randomized Phase 2 clinical trial of laurajerlimab 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:one randomized study.

Speaker 2

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 onetwo dose escalation study of VOVOR DUO in combination with loradirlimab 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 CD123xCD3 DART molecule that incorporates a CD3 component designed to minimize cytokine release syndrome, while maintaining an antitumorcytolytic activity and permitting intermittent dosing through a longer half life.

Speaker 2

Our Phase 1 dose escalation study of MGD-twenty four 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 MGD-twenty four 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 mentioned on prior calls, we have been developing preclinical ADC molecules utilizing linker payload technologies we licensed from Synephix. The first of these is MGC-twenty 6, a clinical ADC incorporating a B7 H3 targeting antibody and a novel topoisomerase 1 inhibitor based linker payload, Syntycan E.

Speaker 2

This cleavable linker payload is based on exotecan, a clinically validated and potent campothecan that readily combines with Synafix HydroSpace technology. We believe Synafix's approach potentially provides advantages visavis other topoisomerase 1 inhibitor based ADCs. In fact, exotecan appears to be more potent and less susceptible to multi drug resistance mechanisms than other top-one inhibitors such as SN38 and deruxotecan. Additionally, site specific conjugation of cintecan to the normally glycosylated amino acid in the Fc domain abolishes Fc gamma receptor and mannose receptor binding, which contribute to non targeted uptake of ADCs in alveolar macrophages and reported to be associated with lung toxicity and therefore may provide a safety benefit for patients. The variable domain of the molecule targeting B7 H3 is the same sequence contained in VOBR Duo.

Speaker 2

We recently initiated a Phase 1 dose escalation study of MGC-twenty six. We view MGC-twenty six as a complementary approach to vopra duo for targeting B7 H3. More specifically, we believe that having distinct mechanisms of action vopra duo and MGC-twenty six 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-one inhibitor strategy as an additional valuable tool in our therapeutic repertoire. We plan to present preclinical data for MGC-twenty 6 at the upcoming American Association For Cancer Research or AACR Annual Meeting next month.

Speaker 2

Here's a preview of what you'll see. In preclinical studies, MGC-twenty 6 exhibited a favorable profile with potent in vivo activity toward B7 H3 expressing tumor xenografts representing a range of cancer indications. Mgc0-twenty 6 was tolerated in cynomolgus monkeys, a relevant toxicology model at exposure levels exceeding those required for anti tumor activity. We look forward to showing you the data set next month. In addition, we are readying a second topoisomerase 1 inhibitor based ADC MGC-twenty 8 for which we currently expect to submit an IND later this year.

Speaker 2

MGC-twenty 8 is a preclinical ADC incorporating an ADAM-nine targeting antibody and the second of our ADC molecules incorporating Synafix's novel linker payload. ADAM-nine or disintegrin and metalloproteinase domain 9 is a member of the ADAM family of multifunctional type 1 transmembrane proteins that play a role in tumorigenesis and cancer progression and is over expressed in multiple cancers making it an attractive target for cancer treatment. MGC-twenty eight is a second ADAM-nine target ADC that we have pursued. The first was IMGC-nine thirty six, a molecule with a metacinoid payload that was advanced under co development arrangement with ImmunoGen, Inc, now part of AbbVie. Under the fifty-fifty collaboration, ImmunoGen led clinical development of IMGC 936.

Speaker 2

Neither MacroGenics nor AbbVie intends to further pursue development of IMGC 936 as the molecule did not achieve our pre established clinical safety and efficacy benchmarks. We plan to present preclinical MGC-twenty eight data at the upcoming AACR Annual Meeting in April. As a preview, MGC-twenty eight exhibited specific dose dependent in vivo anti tumor activity toward ADAM9 positive CDx and PDx models, including in gastric, lung, pancreatic, colorectal and head and neck cancer. MGC-twenty eight was well tolerated in a repeat dose non human primate toxicology study up to 55 milligrams per kg, the highest dose level tested. Of note, ocular toxicities that are typically seen when metansanoid payloads and which we observed in our IMGC 936 synomologous toxicology study were not observed in the MGC-twenty 8 pilotoxicology study.

Speaker 2

We plan to present more preclinical data on this asset at AACR. We currently anticipate submitting an investigational new drug or IND application for MGC-twenty eight by the end of 2024. In addition, beyond MGC-twenty 6 and MGC-twenty 8, we are exploring additional molecules for potential future IND submission. Stay tuned. Finally, enoblituzumab is an Fc optimized monoclonal antibody that targets B7 H3.

Speaker 2

Our academic collaborators have initiated an investigator sponsored randomized, translationally intense, Phase 2 investigator sponsored study of enoblituzumab in up to 219 men with prostate cancer. The HEAT study will evaluate the activity of neoadjuvant enoblituzumab given prior to radical prostatectomy in men with high risk localized prostate cancer. Eligible patients will undergo a pretreatment prostate biopsy and conventional imaging both CT and bone scan as well as PSMA PET and optional prostate MRI as per institutional preferences. To conclude, we believe we have the technical development and clinical expertise as well as financial resources to support our vision of developing and delivering life changing medicines to cancer patients. We would now be happy to open the call for questions.

Speaker 2

Operator?

Operator

Our first question comes from Jonathan Chang with Leerink Partners. Your line is now open.

Speaker 3

Hi, guys. Thanks for taking my questions. First question, can you help set expectations for the preliminary Tamarac data coming up at ASCO? And then second question, can you discuss the rationale behind expanding the Tamarac study to include patients with non small cell lung cancer, small cell melanoma, head and neck and anal cancer? What is informing this decision?

Speaker 3

Thank you.

Speaker 2

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 7,300 molecule at ESMO 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 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 OBERDUO in our expanded approximately 40 patient cohort of about half those patients reducing PSA50 from baseline. Given the dosing right now of 2.7q42q444 and with expectations if the safety is improved as we expect, we should be actually delivering as much or more of the 2.7 mgs Q4 as compared to historical treatment with the 3 mgs Q3. As a result, we expect the PSA50 to be in a similar range, somewhere between 40% 60% PSA50 reduction.

Speaker 2

With regard to overall response rate, again, as we had previously presented, approximately a quarter of patients achieved both confirmed and unconfirmed responses. And this is similar to that which was reported by Daiichi of 25%. So our expectation is we should be 25% or greater. With regard to RPFS, which is the primary endpoint of this study, and a very important one in terms of obviously prolonging both the life and the quality of life of these patients, Daiichi reported 5.3 months of RPFS. And what we have said is that we expect to have at least 6 or greater in terms of RPFS going forward.

Speaker 2

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 5 different tumors now, we are also considering additional tumors in the future to conduct studies.

Speaker 3

Understood. Maybe just a clarifying question 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?

Speaker 2

I would say both. Obviously, given the experience in small cell, for instance, where both Daiichi and Hansel 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 5. 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 am not we're not even limiting it to these 5.

Speaker 2

We are also considering others, which would be very good opportunities for looking at the value of Vopraduo.

Operator

Thank you. One moment for our next question. Our next question comes from Kelsey Goodwin with Guggenheim. Your line is now open.

Speaker 4

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 tracks throughout 2023 and how we should think about follow-up on the 177 patients in the full ASCO presentation?

Speaker 4

Thank you.

Speaker 2

Thank you so much, Kelsey. Because of the timing and I'll discuss enrollment in a second, so it became quite obvious. As I pointed out, we had to do a cutoff date in January for the data submission in early February at ASCO. And as a result, we primarily relied on safety data to be included in the abstract, but also noting that our plan was to present obviously the clinical efficacy data as we were able to accumulate additional data closer to the time of ASCO. Again, to give you a sense of why these decisions were made in terms of the presentations.

Speaker 2

With the amendment of the original Tamarac study, we began to enroll a few patients in the end of the second quarter. But as it turns out, 2 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.

Speaker 4

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.

Speaker 5

Yes, 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 had sufficient experience with the drug?

Speaker 2

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.

Speaker 2

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 sites 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.

Speaker 2

S. Sites continue to enroll, but just because of the proportion that were in Europe compared to Asia and the U. S, the majority got enrolled in Europe in that bolus in the second half of the year.

Speaker 5

Okay. So just to clarify, these were new sites that came online in Europe or were these sites that had already enrolled sufficient?

Speaker 2

No, these are we did 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.

Speaker 2

The majority came in Europe, just the sheer numbers of sites there.

Speaker 5

Okay, understood. And then I guess in kind of baking off the 2.72.0 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?

Speaker 2

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 mid year. 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.

Speaker 2

So, I think it will be a decision that we will arrive at by mid year.

Speaker 5

Okay. And last question, is the maturity of that RPFS statistic rate limiting to your ability then to initiate these additional dose expansion cohorts?

Speaker 2

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 DeRout with BMO Capital Markets. Your line is now open.

Speaker 6

Great. Thanks for taking the question. Just a couple for me here too. Just thinking about the monotherapy, FORWARDUATE study, just if you can maybe start just describing what your thoughts around sort of the pivotal path or development for that in terms of monotherapy or in combination based on what you're observing from Tamarac 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 Voverduo? Thanks.

Speaker 2

Thanks, Etzer. Again, I won't comment on the activity from the Tamarac 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 177 patients dose, the ability 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 3 study would likely to be done in a post chemo experienced population.

Speaker 2

We have now changed that view that clearly if in a chemo naive population, if both the efficacy and the 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 won't make that decision.

Speaker 6

Great. Thank you.

Operator

Thank you. One moment for our next question. Our next question comes from Yigal Nochomovitz with Citigroup. Your line is now open.

Speaker 7

Yes. Hi, Scott and team. 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?

Speaker 2

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 and a half before the submission is ready for presentation. So as you know, the meeting itself is the end of May. I would presume that, they will require us to have the material prepared by mid May.

Speaker 2

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 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.

Speaker 2

But we certainly will provide as much data as we can.

Speaker 7

Okay, thanks. And then a moment ago, you referenced the PFS of at least 6 months as 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 Pluvicta respectively. As we know, those were slightly higher around 8 8.5 months. Are those reasonable expectations or not for what one should expect for Tamarac?

Speaker 2

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.

Speaker 2

And similarly, the activity for the CARDS 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 treat. We just don't know the answer yet. I would 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.

Speaker 8

Hi guys. Thanks for taking the question. I would love to ask about those additional indications that you're moving VOBR DUO into in the Tamarac study. Do you have any additional data from any of those indications in Phase 1 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.

Speaker 8

But previously, you had said you were prioritizing prostate for bandwidth reasons and to sort of competitively be in white space there. So you talk us through a little bit about what changed and why your decision to chase after those indications coming now? And then secondly, I'd love if you could go in a little bit deeper into your differentiation of the new 26 B7 H3 ADC from the other topo-one payload ADC against the same target that are in development?

Speaker 2

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 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.

Speaker 2

We have not had any experience with anal cancer with the Vover Duo and small cell is obvious as I alluded to before based on others' experience there. So those were the initial reasoning behind going after this. And we believe that with the improved potential safety profile of the new dosing regimen, these patients with these other cancers will be able to stay on drug longer to have potentially good outcomes. And that's why we're looking to expand into those indications. Now with regard to 26, 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.

Speaker 2

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 vobraduo in its activity and what we believe to potentially be a superior, topo-one inhibitor, payload based on the Sinofix profile and as I pointed out from various vantage points including increased activity, potency, a less susceptibility to eFlux multidrug resistance, better cell permeability, bystander effect. And the fact as Daiichi has pointed out, many of the interstitial lung disease complications, they are ascribing to binding to alveolar macrophages and by the fact that this Synafix platform eliminates the binding through Fc receptors as well as mass receptors, one should potentially have the ability to reduce a ILD effect with a topo-one inhibitor. So from all these vantage points and from all the things that I described earlier, looking at the ability to treat with vobraduo, looking at potential combinations 0 26 down the line, looking at treatment of different tumors, I think this provides us with a great opportunity.

Speaker 8

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?

Speaker 2

We have not. We have not. 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

Our next question comes from Kaveri Pullman with BTIG. Your line is now open.

Speaker 4

Yes, good evening. Thanks for taking my questions. For the upcoming readout, you will have Wobroduo data for both docetaxel naive and experienced patients. But since you are not going to have mature RPFS data till second half, how are you thinking about making a decision on where to go in terms of a Phase 3 trial?

Speaker 2

Well, good question, Kaveri. Clearly, there will be other metrics that we will be looking at beyond just the RPFS, but there will be a certain number of those patients that will have advanced. We certainly would like to have the full data set to make a final decision. But I think by mid year, we'll know quite well if we're on track for moving forward to a Phase 3 point. And obviously, we don't want to wait to 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.

Speaker 2

So we would just want to be as aggressive as possible once we have at least a large body of data available to us by mid year.

Speaker 4

All right. That's helpful. And then my second question is regarding MGD-twenty four. Any color on when you expect to complete the Phase 1 trial? And how much time Gilead will have to make a decision to opt in once you provide the data?

Speaker 2

So, with regard to 24, 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 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.

Speaker 2

With that, Gilead hasn't until a short period of time after we present the full Phase 1 data to them to opt in on the program. So clearly there's still time. And clearly if they if 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.

Speaker 9

Hi, good afternoon. So I understand the rationale for potentially enabling broad development of OPDUO with the inclusion of pretaxane 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.

Speaker 2

So we will clearly try to provide as 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. I will 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.

Speaker 9

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 6 month versus 8 month expectations come from?

Speaker 9

Are those patients?

Speaker 2

I think you've hit the nail on the head and that's why I'm trying to give a little bit broad brushstrokes on that, on understanding of patients there rapid progressions 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 progress 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.

Speaker 9

Okay. Thank you so much.

Operator

Thank you. One moment for our next question. Our next question comes from Courtney Kowalski with Barclays. Your line is now open.

Speaker 10

Hi, this is Pete Lawson from Barclays. So just a couple of questions. Firstly, in the abstract, will we see safety that's broken out by discontinuation rate and or side effects such as hand for perfusion? And then I've got a follow-up.

Speaker 2

Peter, you will have the discontinuation rate as of that cut of January data. With regard in the abstract itself, I don't recall specifically how deep in terms of the breakdown of the AEs were. I'll have to get back to you on that.

Speaker 10

Got you. Thank you. And then in the TEMAREx study, have patients been exposed to radiopharmaceuticals such as Plavicta? And will you be able to break that out eventually?

Speaker 2

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 Plavicto and the timing didn't work out to get those Plavicto progressors and experienced patients there. We expect a few of them from the U.

Speaker 2

S, but very small numbers there.

Speaker 10

And then just a quick question for Jim on the puts and take around the cash guidance. Just with the expansion of the B7H3 clinical trials kind of I guess that's a negative for cash, but what are the puts and takes we should kind of be thinking about for you to maintain that cash guidance?

Speaker 1

Yes. Thanks, Peter. Thanks for the question. So our guidance of cash runway into 2026 reflects the additional cohorts under the Tamarac umbrella, the additional vobraduoco cohorts. So everything we're talking about, all of these studies that we're currently running and talking about running are all included as part of our guidance.

Speaker 10

Got you. Are there any additional inflows of cash you're thinking through to kind of counterbalance that? Or was that always in the cash guidance?

Speaker 1

Peter, I'm sorry. Could you repeat the question, please?

Speaker 10

Or is there any additional cash inflows that you're thinking us through? Or were those cohorts always in the cash guidance?

Speaker 1

Those cohorts are new to the guidance. There have been some savings. There's always the possibility of additional business development activities. And of course, with $1,000,000,000 in milestones hanging out there related to both tZeal and Zynas, of which we've handicapped significantly, we would anticipate recognition of some of those over the next couple of years.

Speaker 2

And there were some additional revenues coming in that weren't anticipated originally that are part of this guidance.

Speaker 10

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 Turkan with Citizens JMP. Your line is now open.

Speaker 11

Yes, thank you. Thanks for taking my question and congrats on the progress. Maybe piggybacking a little bit on a previous question. What's the bar for the safety profile in the abstract or also at the ASCO presentation versus the safety profile that we've seen on the older doses? And I'm asking in particular maybe on the Grade 3 or higher issues that we've seen with the hand foot map signal and perhaps neutropenia.

Speaker 11

Can you just comment on what you're trying to improve? And is there any bar that makes you confident in the future here? Thank you. And I have a follow-up.

Speaker 2

Sure, Sylvain. 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 be either grade with grade 2 where they have experiencing pain would be electing to come off treatment despite the fact that they were having anti tumor effects.

Speaker 2

And so number 1 is the most important is that we can decrease the incidence totally. And then for those that have with a reduced incidence, 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 febrile neutropenia.

Speaker 2

And so this is mostly handled by holding the drug or stopping the drug. And again, if we can reduce that both in terms of incidence and grade, I think that will be better. But that wasn't as concerning to the treating physicians in managing these patients.

Speaker 11

Great. Thank you. And maybe about the LORIKET 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 vobadu and lagerlumab?

Speaker 2

With regard to the timing of this, we'll provide, as I said earlier, update on the study. It ultimately will depend on the speed in which we can enroll these patients clearly over the next 2 months will be will we exceed 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 2025. But again, we'll be able to give you a little bit more guidance later in the year based on enrollment rates. With regard to the success in this trial, clearly we're testing this in the chemo naive population in combination with docetaxel.

Speaker 2

I think that if that trial is successful, it's a great problem to have if the Vova duo pans out also in that same line of therapy. I should also say that we are not eliminating the possibility that we're going to look at lorikeet I'm sorry, lorogerlimab in later line prostate cancer that is certainly a possibility to consider. But as I have said before, we are also going to look at lorodilumab outside of prostate cancer going forward. So it's just too early to make a decision on registration studies until we have the data.

Speaker 11

Great. Thank you.

Operator

Thank Our next question comes from Yigal Nochomovitz with Citigroup. Your line is now open.

Speaker 7

Hi. Thank you so much for taking the follow-up. Scott, I just had a quick follow-up on Tamarac. It's unusual that you see a trial that's 77% over enrolled relative to the target and enrolled very quickly. Could you just comment on some of the factors that resulted in the heavy over enrollment and as well as the speed to which it was over enrolled?

Speaker 7

Thanks.

Speaker 2

Yes. So, Yigal, with regard to our decision on letting so many more patients into the study, is 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.

Speaker 2

As I was pointing out, some of the amendments included the fact that we didn't require 12 months of treatment on an ARAT. And so patients who were progressing quickly were able to join the study and they probably did not have much in terms of other alternatives. There also it turns out to be a large number of patients for varying reasons, whether they're not qualified to go on docetaxel or chemotherapeutic or they choose not to, I think we attracted a large number of those patients into the study that allowed us to have a very sizable subpopulation of chemo naive patients.

Speaker 7

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.

Speaker 2

Well, thank you very much for participating in the call today. We look forward to obviously updating you at ASCO in the near term and talk to you at future times on earnings calls and in other venues. Thank you very much.

Operator

This concludes today's conference call.

Remove Ads
Powered by Quartr
Earnings Conference Call
MacroGenics Q4 2023
00:00 / 00:00
Remove Ads