MacroGenics, Inc. (NASDAQ:MGNX) Q1 2024 Earnings Call Transcript

MacroGenics, Inc. (NASDAQ:MGNX) Q1 2024 Earnings Call Transcript May 10, 2024

MacroGenics, Inc. isn’t one of the 30 most popular stocks among hedge funds at the end of the third quarter (see the details here).

Operator: Good afternoon. We will begin the MacroGenics 2024 First Quarter Corporate Progress and Financial Results Conference Call in just a moment. [Operator Instructions] At this point, I will turn the call over to Jim Karrels, Senior Vice President, Chief Financial Officer of MacroGenics.

Jim Karrels: Thank you, operator. Good afternoon, and welcome to MacroGenics’ conference call to discuss our first quarter 2024 financial and operational results. For anyone who has not had the chance to review these results, we issued a press release this afternoon outlining today’s announcements. This release is available under the Investors tab on our website at macrogenics.com. You may also listen to this conference call via webcast on our website, where it will be archived for 30 days beginning approximately 2 hours after the call is completed. I would like to alert listeners that today’s discussion will include statements about the company’s future expectations, plans and prospects that constitute forward-looking statements for purposes of the Safe Harbor provision under the Private Securities Litigation Reform Act of 1995.

Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in the Risk Factors section of our annual, quarterly and current reports filed with the SEC. In addition, any forward-looking statements represent our views only as of today and should not be relied upon as representing our views as of any subsequent date. While we may elect to update these forward-looking statements at some point in the future, we specifically disclaim any obligation to do so even if 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, including an important interim data update on our TAMARACK Phase 2 study 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 quarter ended March 31, 2024 which highlight our financial position. As described in our release this afternoon, MacroGenics total revenue was $9.1 million for the quarter ended March 31, 2024, compared to total revenue of $24.5 million for the quarter ended March 31, 2023. This decrease was primarily due to a decrease in revenue from collaborative and other agreements, including a $15 million milestone received from Incyte in the quarter ended March 31, 2023. Our research and development expenses were $46 million for the quarter ended March 31, 2024, compared to $45.9 million for the quarter ended March 31, 2023. Our selling, general and administrative expenses were $14.7 million for the quarter ended March 31, 2024, compared to $13.5 million for the quarter ended March 31, 2023.

The increase was primarily related to increased stock-based compensation expense and consulting fees. Our net loss was $52.2 million for the quarter ended March 31, 2024, and compared to a net loss of $38 million for the quarter ended March 31, 2023. Our cash, cash equivalents and marketable securities balance as of March 31, 2024, was $184.2 million compared to $229.8 million as of December 31, 2023. Finally, in terms of our cash runway, consistent with our prior guidance, we anticipate that our cash, cash equivalents and marketable securities balance of $184.2 million as of March 31, 2024 and in addition to projected and anticipated future payments from partners and product revenues should provide a cash runway into 2026. Our anticipated funding requirements reflect expected expenditures related to the ongoing Phase 2 TAMARACK and LORIKEET studies as well as our other ongoing clinical and preclinical studies.

And now I’ll turn the call back to Scott.

Scott Koenig: Thank you, Jim. We continue to believe our proprietary pipeline of product candidates has great promise, and I will walk you through each of our key programs, including disclosure of new safety and efficacy data from the TAMARACK study of vobramitamab duocarmazine in patients with metastatic castration-resistant prostate cancer. We have lots to cover today, so let’s jump in. Vobramitamab duocarmazine or vobra duo is our ADC designed to deliver a DNA alkylating duacomyocin cytotoxic payload to tumors expressing B7-H3. B7-H3 is a member of the B7 family of molecules involved in immune regulation. Vobra duo designed to take advantage of this antigen’s broad expression across multiple solid tumor types. As you know, we believe B7-H3 has the attributes of an ideal cancer target.

The TAMARACK study is being conducted in mCRPC patients, where previously received an androgen receptor access targeted agents or ART and up to 1 prior taxane containing regimen but no other chemotherapy agents. The study is designed to evaluate vobra duo patients across 2 experimental arms of either 2 mg per kg or 2.7 mg per kg every 4 weeks with radiographic progression-free survival, or rPFS, as the study’s primary endpoint. We recently generated an updated expanded interim data set based on a data cut off date of April 12, 2024, which is the basis for all of the TAMARACK data we are sharing with you today. Feel free to download the slide set that highlights this data from the Events and Presentations page under the Investor Relations section of our website or you can find the direct link to the document provided in today’s earnings press release.

Flip ahead to Slide 4, and you will note we have enrolled a total of 181 patients although a few patients were on the original control arm and are thus not counted in the safety population of 176 patients who receive vobra duo. This is 1 less than the 177 we mentioned in an earlier press release, as 1 patient never fully completed the informed consent form process. As you can see on this slide, we’ve broken out the number of patients with a valuable PSA and baseline target lesions by dosing cohort. Slide 5 provides several baseline characteristics. Both arms are well balanced with the exception of ECOG status as the 2.7 mg per kg arm very slightly favors ECOG 1 over ECOG 0. Keep in mind that this is a fairly subjective measure. I’ll point out that despite randomization, fewer patients in the 2.7 mg per kg cohort and measurable disease than not measurable, whereas there was roughly 50-50 split in the 2 mg per kg cohort.

In terms of having a prior taxane versus not, the split was close to 60-40 across both those cohorts. Also recall that mCRPC patients had to have a prior androgen receptor access targeted agents for study entry. And as you can see, a few had more than one. Next, let’s review biological activity. On Slide 6, we show the PSA50 responses for 153 patients, which represents all subjects who had received at least 1 dose of – over – do at a baseline PSA greater than 2 nanograms per ml and had at least 1 post-baseline PSA measurement. For the 2 mg per kg dosing cohort, 50% of the 82 evaluable patients experienced a greater than 50% reduction in their PSA while 43.9% of patients had a confirmed greater than 50% PSA reduction. In the 2.7 mg per kg dosing cohort, 50.7% of 71 evaluable patients experienced a greater than 50% reduction in their PSA while 36.6% of patients had a confirmed greater than 50% PSA reduction.

Happily, these PSA50 results are generally well aligned with the PSA50 expectations we laid out before the study commenced. Turning to the summary of 2 responses as summarized on Slide 7 and among the 45 patients with baseline target lesion measurements in the 2 mg per kg dosing cohort, 41 or 91.1% achieved disease control as measured by some of confirmed complete and partial responses plus stable disease, while the confirmed objective response rate as measured by some of complete and partial responses or 17.8%. With the inclusion of unconfirmed CRs and PRs, the unconfirmed ORR was 24.4%. Among the 32 patients with baseline target lesion measurements in the 2.7 mg per kg dosing cohort, the disease control rate was 87.5%. The confirmed ORR was 25% and with the inclusion of unconfirmed PRs and CRs, the unconfirmed ORR was 43.8%.

Let’s review the PSA waterfall plot next. Slide 8 shows the PSA waterfall plot for the 2 mg per kg cohort. As you can see, 41 of the 82 patients had a 50% or greater decrease in PSA with 36 or 43.9% of these patients achieving a confirmed PSA50 response. 48 of these patients or 58.5% remained on therapy as of the data cutoff. Also based on the archival biopsy B7-H3 membrane H scores shown on the plot, it does not appear that there are B7-H3 expression thresholds required for reducing PSA. We are still reviewing this interim data. At this point, the implication is that B7-H3 biomarker diagnostic will likely not be required. Slide 9 shows the PSA waterfall plot for the 2.7 mg per kg cohort. Here, 36 of the 71 patients had a 50% or greater decrease in PSA with 26 or 36.6% of these patients achieving a confirmed PSA50 response.

As of the data cutoff, 39 patients or 54.9% of patients remained on therapy. Next, I will review investigator-assessed tumor size waterfall plots. On Slide 10, which shows the 2 mg per kg cohort, of the 45 patients with measurable disease, 1 did not have a post-baseline tumor assessment. As I mentioned earlier, the disease control rate for this group was 91.1%, with all but 3 patients having either a partial response or stable disease. The confirmed ORR was 17.8%, while the unconfirmed ORR was 24.4%. Slide 11 shows tumor response for the 2.7 mg per kg cohort. Here of the 32 patients with measurable disease, 2 did not have a post-baseline tumor assessment. The disease control rate for this group was 87.5%. The confirmed ORR was 25%, while the unconfirmed ORR was 43.8%.

Next, I will review the swimmer plot for the tumor response, which will hopefully convey a sense of durability of vobra duo in the mCRPC setting. Slide 12 shows the interim results for the 2 mg per kg cohort. Here you can see that of the 45 tumor response evaluable patients, 8 or 17.8% had confirmed responses with the inclusion of the 3 unconfirmed responses, the unconfirmed ORR is 24.4%. 23 of the 45 patients or 51.1% were still on therapy as of the data cutoff. In the 2.7 mg per kg dosing cohort, shown on Slide 13, 8 patients or 25% had confirmed objective responses with these 6 unconfirmed responses, the unconfirmed ORR is 43.8%. 20 of the 32 patients or 62.5% remained on therapy as of the data cutoff. Next, I will review interim safety in the TAMARACK study as of the data cutoff.

Slide 14 shows the overall summary of adverse events in this study to date. I’ll point out a few parameters by dosing cohort. Of the 90 patients who receive overdue are at 2 mg per kg 89 or 98.9% experienced study treatment-emergent adverse events of any grade or 54.4% of the patients had a great 3 or greater TEAE and 10 patients or 11.1% and an adverse event leading to study drug discontinuation. Of the 86 patients who received vobra duo duo at 2.7 mg per kg, 86% or 100% experienced a TEAE of any grade, 44 or 51.2% of patients at a Grade 3 or greater TEAE and 13 patients or 15.1% at an AE leading to study drug discontinuation. Also, as noted on Slide 14, as of the data cutoff date, a total of 5 fatal events occurred as follows: 1 Grade 5 fatal event occurred in the 2 mg per kg dosing cohort, an acute myocardial infarction, which was not classified as treatment related, 4 Grade 5 events occurred in the 2.7 mg-per-kg dosing cohort, which included 1 cardiac arrest, not classified as treatment related and two cases of pneumonitis, which are still being investigated and initially assessed as possibly treatment related.

In addition, a patient on 2.7 mg per kg dosing cohort had a grade 3 plural fusion and subsequently died. In terms of specific treatment-emergent adverse events those with incidents greater than or equal to 10% as shown on Slide 15, for the 2 mg-per-kg dosing cohort, the 5 most common TAs of any grade in this dosing cohort included Asthenia, Nausea, Peripheral Oedema, Decreased Appetite and Fatigue. Of note, the incidence of Pleural Effusion in this cohort was Grade 1 of 8.9% and Grade 2 of 0.9%. There were no Grade 3 or greater events. Also, the incidence of palmar-plantar erythrodysesthesia syndrome in this cohort was a Grade 1 of 11.1% and Grade 2 of 4.4%. There were no Grade 3 or greater events. The 5 most common TEAEs of any grade in the 2.7 mg-per-kg dosing cohort included Asthenia, Decreased Appetite, Peripheral Oedema, Nausea and Pleural Effusion.

Of note, the incidence of Pleural Effusion in this cohort was Grade 1 of 14.0%, Grade 2 of 14.0% and Grade 3 of 1.2%. Also, the incidence of palmar-plantar erythrodysesthesia syndrome in this cohort with Grade 1 of 12.8%, Grade 2 of 9.3% and Grade 3 of 1.2%. As visually represented in the butterfly plot on Slide 16, all the TEAEs of greater than or equal to 10% of are overwhelmingly limited to either Grade 1 or 2. Overall, we believe these doses are tolerable with side effects that are manageable. Also, we are very pleased with the biological activity observed in the study as of April 12, 2024 data cutoff with the interim data being well aligned with the parameters of success that we laid out at the onset of the study. We achieved our goal of reducing the incidence and severity of both palmar-plantar erythrodysesthesia and pleural effusion in comparison as of the most recent data cut off to what we saw in the Phase I dose expansion study.

We will continue to evaluate the totality of the data, including future radiographic progression-free survival or rPFS the study’s primary endpoint as we consider dose selection of either 2 mg per kg or 2.7 mg per kg. To that end, we are currently undertaking the necessary initial steps to prepare for the potential initiation of a Phase 3 study in mCRPC in 2025. Looking ahead, we plan to share updated TAMARACK safety, efficacy and durability data, including rPFS in the second half of 2024 based on a future data cutoff. Also, as mentioned on our prior earnings call, we plan to expand the tumor types being evaluated in the TAMARACK trial and expect to 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. Recall, that we have 2 other clinical molecules that target B7-H3. The first, MGC026 is an investigational ADC incorporating a novel topoisomerase 1 inhibitor based linker-payload SYNtecan E, which we licensed from Synaffix. Our second additional B7-H3 targeted molecule is enoblituzumab, an investigational Fc-optimized monoclonal antibody. I’ll walk you through both of these molecules next. MGC026 incorporates the linker-payload based on exatecan, a clinically validated and potent cantatecan that readily combines with Synaffix’s Hydraspace technology. MGC026 preclinical data was presented recently at the American Association for Cancer Research Annual Meeting. In preclinical studies, MGC026 was shown to have greater potency than B7-H3-directed antibodies conjugated to deruxitecan or DXd, a topoisomerase as payload utilized in other ADCs. In addition, the MGC026 payload has been shown to be less susceptible to multi-drug-resistant mechanisms than DXd and SN-38.

Also, our toxicology study conducted in cynomolgus monkeys show that MGC026 was well tolerated at all dose levels tested. Finally, MGC026 displayed approximate dose proportion of pharmacokinetics in the animal models tested, indicating predictable behavior of conducive to further clinical development. We recently initiated a Phase 1 dose escalation study of MGC026. The variable domain of the molecule targeting B7-H3 for MGC026 is the same sequence contained in Vobra duo. We view MGC026 as a complementary approach to Vobra duo for targeting B7-H3. More specifically, we believe that having distinct mechanisms of action while Vobra duo and MGC026 may address different cancers tumor stages or be used in combination with ultimate agents or potentially with one another to enhance their clinical utility.

We remain confident in the potential of targeting the B7-H3 pathway viewing our TOPO 1 inhibitor strategy as an additional valuable tool in our therapeutic repertoire. Regarding Enoblituzumab, our academic collaborators are enrolling an investigator-sponsored, randomized translationally intense Phase 2 investigator-sponsored study of this molecule in up to 219 patients with prostate cancer. The HEAT study is evaluating the activity of neoadjuvant and 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, including CT and bone scan as well as PSMA PET and optional prostate MRI as per institutional preferences. Next, I’ll update you on Lorigerlimab, our bispecific tetravalent PD-1 by CTLA-4 dark molecule.

We designed Lorigerlimab to have preferential blockade on dual PD-1 CTLA-4 expressing cells, such as tumor infiltrating lymphocytes, which are most abundant in the tumor micro environment. We are enrolling the LORIKEET study a randomized Phase 2 clinical trial of Lorigerlimab in combination with docetaxel versus docetaxel alone in second-line chemotherapy naive mCRPC patients. A total of 150 patients are planned to be treated in the 2:1 randomized study. The current study design includes the primary study endpoint of rPFS. We anticipate completing enrollment of the study this year and expect to provide a LORIKEET clinical data update in the first half of 2025. In addition, we continue to enroll patients in the Phase 1, 2 dose escalation study of Vobra duo in combination with Lorigerlimab in patients with advanced solid tumors.

We anticipate commencing a dose expansion study of this combination in mCRPC and at least one additional indication in 2024. Next up, MGD024 is our next-generation bispecific CD123 x CD3 DART molecule that incorporates the CD3 component designed to minimize cytokine release syndrome while maintaining antitumor cytolytic activity and permitting intermittent dosing through a longer half-life. Our Phase 1 dose escalation study of MGD024 is ongoing in patients with CD123 positive relapsed or refractory hematologic malignancies, including acute myeloid leukemia and myelodysplastic syndromes. Recall that Gilead has the option to license MGD024 and predefined decision points during the Phase 1 study. In terms of preclinical projects, MGC028 is our second topoisomerase 1 inhibitor based ADC incorporating Synaffix novel linker-payload and an ADAM9 targeting antibody.

ADAM9 is a member of the Adams family a multifunctional type 1 transmembrane protein that play a role in tumor genesis and cancer progression and is overexpressed in multiple cancers, making it an attractive target for cancer treatment. We recently presented MGC028 preclinical data at the AACR Annual Meeting in April. In preclinical studies, MGC028 demonstrated specific antitumor activity in vivo models representing gastric, lung, pancreatic, colorectal, small cell carcinoma, the head and neck and Cholangiocarcinoma. In addition, in a non-human primate study, MGC028 was well tolerated at high dose levels with mild reversible side effects and no ocular toxicity which is offered a concern with Tubulin inhibitor based ADCs. These promising preclinical results support the continued investigation of MGC028 as a therapeutic option for treating ADAM9 solid tumors.

We are currently anticipating submitting an investigational new drug or IND application for MGC028 by the end of this year. Beyond MGC028, we are exploring additional molecules for potential future IND submission. I look forward to telling you more about these additional molecules on future calls. To conclude, – we believe MacroGenics has the technical development and clinical expertise as well as financial resources to support our vision of developing and delivering life-changing medicines to cancer patients. We would now be happy to open the call for questions.

Operator: [Operator Instructions] Our first question comes from the line of Tara Bancroft with TD Cowen.

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Q&A Session

Tara Bancroft: Hi, good afternoon. So lots of questions here, I’m sure. But – so looking at the safety, it does look somewhat similar to the Phase 1 now with these two extra cycles versus the abstract. So could you elaborate more on what it is that you’re seeing as improved in terms of safety with these doses? Or is it what you’re referring to more on the efficacy side and how this looks like quite different from the abstract with these just to more median cycles? So could you describe more what happened there?

Scott Koenig: Well, actually, Tara, let me sort of go through the safety. First of all, the safety data cut was in January, and now we’re in April, greater than 3 months since the January cutoff. We are – first of all, compared to the Phase 1 data, we are now exceeding the mean number of doses that were achieved in the Phase 1 study. And then second – third is if you look at the butterfly plot of the AEs, the side effects of overwhelmingly Grade 1 or 2 manageable with a smattering of Grade 3 concerning new type of side effects has propped up as you see on the figure or in the listings in this interim data set. And as you note on both the PSA figures as well as the figures we included on the targeted lesion figures, the majority of these individuals are still on study.

we are clearly in the Phase 1, they were coming off study. We did a head-to-head analysis at 16 weeks of all patients that are on TAMARACK and compared it to the prostate patients on the Phase 1 study also at 16 weeks. And the results in TAMARACK are dramatically improved. For example, specifically, we had half the amount of Grade 3s in TAMARACK as compared to the Phase 1 prostate group. One-half to one-third of the total of discontinuations and about half of the reductions in TAMARACK as compared to the Phase 1 and only one-third to one-half of drug interruptions. So as we have laid out in terms of achieving this vis-a-vis the Phase 1 study, we are – we have accomplished what we wanted to achieve. Furthermore, we did some key comparisons to other prostate studies.

For example, in our discontinuation rates at the 11% at 2 mgs or the 15% of the 2.7 mg. This compares well to a number of other studies. For example, in the CARD study cabazitaxel, there was a discontinuation rate of 19.8%. In KEYNOTE 921, the docetaxel arm was 22.4%. And similarly, the combo arm with pembro was 29.2% and then in TRITON3 for the dose arm, it was 32.4%. So as you see, we’re doing quite well there with regard to discontinuations vis-a-vis others. And similarly, for Grade 3 we can compare what we’re seeing here, for instance, in the docetaxel arm in TRITON3, 61% KEYNOTE-091 36%. And then if you even look at experimental Phase 1 studies in prostate, some new targets, if you look at Amgen’s steep by CD3 was 55% and then Daiichi 7300, it was 47% in the prostate.

So overall, again, as I pointed out, while the safety data has accumulated more safety side effects, we believe that these are extremely manageable the discussions with investigators, they are very comfortable with managing these patients and are very encouraged by the – both the safety and obviously, the activity data they’ve seen to date.

Tara Bancroft: Okay, thank you, that’s super helpful. Thanks.

Operator: Our next question comes from the line of Jonathan Chang with Leerink Partners.

Jonathan Chang: Hi, guys. Thanks for taking my questions. I guess I’m also just trying to better understand the evolution and the tolerability profile versus the previously submitted abstract. Is there a time dependency to the AEs or does this evolution reflects something else? And then second question, can you provide any additional color on the patient deaths and whether or not they were treatment-related. Thank you.

Scott Koenig: Yes. Thanks. So again, as I started off with a question from Tara, the cutoff from – and the safety was of as of January – beginning of January, and as we did a comparison between the original Phase 1 prostate data and that of the data that we had as of the January cutoff we looked at the 95 patients that had reached the 12 weeks. So that was a head-to-head comparison of where the safety was at that point versus that of the Phase 1 study. And so as I said before, the data will continue to accumulate. We now have data – safety data on the entire population over now greater than 3 more months of data that’s accumulated. But again, as I reiterate, look at the butterfly part where we have a very safety data that’s limited to Phase 1/2 quite manageable going forward.

And as I was pointing out earlier – this is not that different from what has been seen with other ADCs as well as other agents that have been approved in prostate cancer. So that’s the summary there. With regard to the patient deaths, as pointed out, cardiac death and a cardiac arrest were not deemed to be associated with the drug unrelated. The additional cases of – two cases of pneumonitis are being investigated. These are sort of real-time observations in the 2.7 mg per kg cohort. What we can say is that particularly one of these cases was very complicated with other confounding matters – medical matters with this patient but we’re – it’s being further investigated right now, so I don’t have a further decision with regard to a positive effect with regard to drug.

And similarly, the patient that was deemed with a plural effusion, the occurrence of that death occurred more than 3 months later. And again, it’s being investigated at this time.

Jonathan Chang: Got it. thanks for taking my questions.

Operator: Our next question comes from the line of Yigal Nochomovitz with Citi.

Ashiq Mubarack: Hi, guys. This is Ashiq Mubarack on for Yigal. Thanks for taking my questions. A few from me. I guess on the Grade 5 pneumonitis in ended, were you surprised that these occurred. I can’t quite recall if neonates been observed as a signal previously. And to that end, is there a B7-H3 expression in the lungs? And are you considering maybe integrating some type of steroid prophylaxis to help prevent pneumonitis moving forward?

Scott Koenig: Again, as I was indicating, these are still being investigated. So the cause and effect with regard to the drug is still under investigation. And we have not – and in fact, we have not seen in the large number of patients here any association with pneumonitis in that patient. So that again, raises questions of what is the ultimate cause of these patients associated with the pneumonitis. Let me just finish – I’m sorry, I didn’t finish your second question, which was expression of B7-H3 in the lung, not normally seen in the lung – we had no lung findings in the cynomolgus monkey toxicology studies. Clearly, with certain activation, you can have certain cells that may have expression of B7-H3, but it’s not a normal occurrence.

Ashiq Mubarack: Okay. Okay. Got it. And then maybe another question. I mean, how are you thinking about choosing the dose moving forward into Phase 3? I know it seems a little confounding. It seems like efficacy is balanced on PSA50, but ORR a little bit higher at the higher dose, but maybe the safety is a little better at the lower dose. So how are you thinking about that?

Scott Koenig: Well, I think that’s exactly the point here is that we’re seeing a nice gradation. We believe that we have picked the correct dosing range to evaluate what will be the optimal dose. And so this will be determined when we achieve the rPFS values and the disease control rate values, which we expect to happen towards later in the midyear. So stay tuned for that. But as we view the data right now, both doses are potentially usable and further developable going forward with this interim data.

Ashiq Mubarack: Got it. Thanks very much.

Operator: Our next question comes from the line of Kaveri Pohlman with BTIG.

Kaveri Pohlman: Hi. Yes, good evening. Thanks for taking my questions. Can you comment on how the efficacy and safety look like in chemo pretreated versus chemo naive patients, if you saw any notable differences there?

Scott Koenig: Thank you Kaveri for that question. And I’m not going to comment on that, but what I would say at this point is that both populations, both the chemo-naive and the chemo experience populations are under consideration for development as we go forward into the Phase 3 study. and nothing unexpected was observed with regard to either populations in terms of overall responses.

Kaveri Pohlman: Got it. And then is there any feedback you received from physicians regarding dose reduction, interruption grade, the reduced level of doses that were used and their potential to impact durability?

Scott Koenig: Well, again, as we’ve shown very nicely and we wanted to illustrate that on the swimmers part, that these patients have sustained responses and continue even on the circumstances when doses had been modified and reduced. As you looked on some of the longer treated patients – We had, as you saw in patients with 2.7 mg per kg and a patient on the 2 mg that were over 30 weeks of treatment there was some dose reductions there. And again, patients are doing quite well. So they are very comfortable and with experiences in using other chemotherapies, for example, on doing dose modification, and we have seen that this is – has not led to any mitigation or reduction in responses so far as of this interim data.

Kaveri Pohlman: Got it. That’s helpful. And maybe a last one. Any thoughts on why there is no correlation between efficacy and B7-H3 expression?

Scott Koenig: Well, that was something we pointed out on the Phase 1 study. We did not see that either. We were observing responses even in patients that had lower H scores, although this may be a situation that it’s a threshold effect where you – if you have a modest number of expression of B7-H3, that’s sufficient to provide entry of the of the linker toxin into the cells. So we see that as actually a positive result here. The caveat is, of course, these are our primal specimens. And there may be some differences if you do fresh biopsies.

Kaveri Pohlman: Got it. Helpful. Thanks for taking my questions.

Operator: Our next question comes from the line of Stephen Willey with Stifel.

Stephen Willey: Yes. Good afternoon. Thanks for talking the questions. Just with respect to the pneumonitis, I know that this is typically something that needs to be proactively looked for, whether it’s via chest x-ray or CT. And just I’m curious if that was kind of a routine screening procedure to some of these patients and could some of the higher rates of dyspnea that are observed in the 2.7 arm, including some of the grade 3 plus events. Could those be I guess, maybe miscategorized as as pneumonitis in the context of perhaps not proactively screening for it?

Scott Koenig: I don’t believe that there is a screening protocol for this because, a, as I pointed out earlier, there was no observed increased rate of pneumonitis in the population. With regard to a patient that has dyspnea, they would normally get as part of their treatment. Although I can’t comment on the specific patients here is obviously a full workup and clearly, there are a lot of different causes of dyspnea, although again, the percentages are quite low. So again, I’ll just reiterate the cases of pneumonitis are under investigation. And clearly, there are at least the data to-date other complicating factors of one of the patients with pneumonitis of other medical issues. And we still need to get additional information on the other patients. So too early to draw any conclusions.

Stephen Willey: Okay. And I’m not sure if it’s in the presentation, but can you also provide us with what the median duration of follow-up is in both of these – in both of these arms at this point?

Scott Koenig: It was – there was – the time we don’t have included here, and I don’t know off the top of my head, but – and what we do is, obviously, you saw on the swimmers plot the time and a large number of these – significant of these patients have exceeded the 16 to 20-week time interval the number of doses – the mean number of doses is now five. So which is on…

Stephen Willey: And then just lastly, I know this trial allowed for patients who had not been on, I guess, stable API for 12 months. Do you know how those patients attribute out between the 2 treatment arms with respect to patient based lines?

Scott Koenig: With regard to that population, if I – without – I don’t have the specific percentages in front of me. But as I recall, I believe it was about a 40% to 60% split in terms of less than 12 months, greater than 12 months of historical DART exposure in that regard.

Stephen Willey: Thanks for taking the questions.

Operator: Our next question comes from the line of John Miller with Evercore.

John Miller: Hi, guys. Thanks for taking the questions. Very interesting update here. Scott, I would love to get a little bit more confirmation. I know you said in response to an earlier question that you saw interruptions and discontinuations looking better than Phase 1, but that – I want to confirm that you said that and what exactly number you’re pulling from. When I look at the Phase 1 poster I see 15% discontinuations, 59% interruptions, that looks right in line with what we’re seeing with today’s update at 15%, 56% of the 2.7 mg per kg arm there. And for hand foot syndrome, while, obviously, the grading appears to be lower in this update. You’re seeing 31% in the Phase 1 result going to 23% of the 2.7 mg arm today.

So when you look at the tox signals, versus Phase 1, you’d characterize them as being much better than they were, but I would love to see Like, is there a place – this particular number you can point to say, look, this is where it got better. This is where docs are going to be comfortable dosing this this is the lynchpin number that is going to let people stay on therapy longer than they did in Phase 1.

Scott Koenig: Yes. So the – again, I want to compare apples-to-apples here. And so I’m comparing as we did in the previous safety data reveal from the abstract it was a comparison to the prostate cohort. I believe what you were pulling out is all different populations. So, I am just looking and I know the specific data. And what I said before is absolutely correct that in the patients in the Phase 1 study whether you look at severity of Grade 3, whether you look at drug discontinuations, whether you look at drug dose reductions, whether you look at drug interruptions, the percentage of those patients in the Phase 1 study was anywhere from greater than 2x of what we are seeing at the same time interval around 16 weeks. I am trying to as best do an apples-to-apples comparison from a time exposure to drug.

And there could be some modest variations of what the ultimate drug exposure was. But I am clearly seeing at least 2x to 3x more of the side effect profiles and severity of grades in the Phase 1 prostate on versus what we are seeing here in TAMARACK. And so again, I will reiterate the feedback we are getting from the investigators has been manageable tolerability not concerning. And in addition, as I have pointed out earlier, we are now past of where the mean number of doses in this TAMARACK is vis-à-vis where we were in the Phase 1 study. And so I am feeling very encouraged and that we are on the right pathway here for delivering this drug. And as I showed in the various spider plots [ph], the majority of the patients are still on treatment despite some of the dose modifications and interruption.

John Miller: Alright. I guess I understand that. Can – maybe on the efficacy side, I would look to – I don’t see in the deck how many prior lines of therapy, what’s the median prior line of therapy in these cohorts, and then what are you looking at for the comps for ORR and DCR in that population?

Scott Koenig: So, here, as I pointed out, the entry criteria was no more than three lines of therapy. I don’t know where it ended up on – with regard to the median for this study, whether it was two or three. But we will have to get back to you on that. Again, in terms of the ORR, I mean if you listened as you have to some of the continuous guidance I had which I started back in November, we were seeing approximately a 25% confirmed-unconfirmed rate of objective responses and what was observed in the Daiichi 7300 in the ESMO presentation was a solid 25% as well. The point I made was that we should certainly achieve the 25% by the end of the study. And as we see here, not only are we achieving it, it is likely we are going to exceed this when the final data comes out, given that, as I pointed out, many of these patients are still on study, but we have a confirmed and uncomfortable ORR in the 2.7 mg per kg of 43.8%.

And in the 2.0 Q4 in the confirmed or not confirmed a 24.4%. So, I think we are doing quite well with regard to what the expectations were and what the data is as of this cut. But again, continue to expect further maturation of this data and continuing improvement.