BK Technologies Q1 2024 Earnings Call Transcript

Quartr
Provided by Quartr
May 9, 2024

There are 13 speakers on the call.

Operator

Good afternoon. We will begin the MacroGenics 20 24 First 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 Q1 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.

Speaker 1

I would like to alert listeners that today's discussion will include statements about the company's future expectations, plans 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 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, including an important interim data update on our Tamarac 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.

Speaker 1

Thank you, Scott. This afternoon, MacroGenics reported financial results for the quarter ended March 31, 2024, which highlight our financial position. As described in the release this afternoon, MacroGenics' total revenue was $9,100,000 for the quarter ended March 31, 2024 compared to total revenue of $24,500,000 for the quarter ended March 31, 2023. This decrease was primarily due to a decrease in revenue from collaborative and other agreements, including a $15,000,000 milestone received from Incyte in the quarter ended March 31, 2023. Our research and development expenses were $46,000,000 for the quarter ended March 31, 2024 compared to $45,900,000 for the quarter ended March 31, 2023.

Speaker 1

Our selling, general and administrative expenses were 14 point $7,000,000 for the quarter ended March 31, 2024 compared to $13,500,000 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 $52,200,000 for the quarter ended March 31, 2024 compared to a net loss of $38,000,000 for the quarter ended March 31, 2023. Our cash, cash equivalents and marketable securities balance as of March 31, 2024 was $184,200,000 compared to $229,800,000 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 $184,200,000 as of March 31, 2024, in addition to projected and anticipated future payments from partners and product revenues should provide a cash runway into 2026.

Speaker 1

Our anticipated funding requirements reflect expected expenditures related to the ongoing Phase 2 tamarack and lowercase studies 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 and I will walk you through each of our key programs including disclosure of new safety and efficacy data from the Tamarac study of obrimitimabduacarmizine in patients with metastatic castration resistant prostate cancer. We have lots to cover today, so let's jump in. Vobramidumabduacarmizine or vobraduo is our ADC designed to deliver a DNA alkylating duorkomycin cytotoxic payload to tumors expressing B7 H3. B7 H3 is a member of the B7 family of molecules involved in immune regulation.

Speaker 2

Vopraduo was 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 Tamarac study is being conducted in mCRPC patients where previously received an androgen receptor active targeted agent or ARAT and up to one prior taxane containing regimen with no other chemotherapy agents. The study is designed to evaluate vopraduo in patients across 2 experimental arms of either 2 mgs per kg or 2.7 mgs 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 cutoff date of April 12, 2024, which is the basis for all of the Tamarac data we are sharing with you today.

Speaker 2

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 OPDUO. This is one less than the 177 we mentioned in an earlier press release as one 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.

Speaker 2

Both arms are well balanced with the exception of ECOG status as the 2.7 mg per kg arm very slightly favors ECOG1 over ECOG0. Keep in mind that this is a fairly subjective measure. I'll point out that despite randomizations, fewer patients in the 2.7 mgs per kid cohort and measurable disease than non measurable, whereas there was roughly fifty-fifty split in the 2 mix per kid cohort. In terms of having a prior taxane versus not, the split was close to sixty-forty across both those cohorts. Also recall that mCRPC patients had to have a prior androgen receptor access targeted agent for study entry.

Speaker 2

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 one dose of OVA DUO, had a baseline PSA greater than 2 nanograms per ml and had at least 1 post baseline PSA measurement. For the 2 mgkg 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.

Speaker 2

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 in Slide 7. Among the 45 patients with baseline target lesion measurements in the 2 mgkgdosing cohort, 41 or 91.1 percent complete and partial responses plus stable disease, while the confirmed objective response rate as measured by sum of complete and partial responses was 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%.

Speaker 2

The confirmed ORR was 25% and with the inclusion of unconfirmed PRs and CR, the unconfirmed ORR was 43.8%. Let's review the PSA waterfall plots 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 PSA 50 response. 48 of these patients or 58.5 percent remained on therapy as of the data cutoff.

Speaker 2

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 a B7 H3 biomarker diagnostic will likely not be required. Slide 9 shows the PSA waterfall plot for the 2.7 mg per kid 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.

Speaker 2

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 MYC per kid cohort, of the 45 patients with measurable disease, one 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%.

Speaker 2

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 plots for the tumor response, which will hopefully convey a sense of durability of VovaDuo in the mCRPC setting.

Speaker 2

Slide 12 shows the interim results for the 2 mg per kid 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 percent were still on therapy as of the data cut off. In the 2.7 mg per kg dosing cohort shown on Slide 13, 8 patients or 25% had confirmed objective responses.

Speaker 2

With these 6 unconfirmed responses, the unconfirmed ORR is 43.8%. 20 of the 32 patients or 62.5 percent remained on therapy as of the data cut off. Next, I will review interim safety in the Tamarac study as of the data cut off. Slide 14 shows the overall summary of adverse events in the study to date. I'll point out a few parameters by dosing cohort.

Speaker 2

Of the 90 patients who receive OPDUO at 2 mix per kg, 89% or 98.9% experienced the study treatment emergent adverse events of any grade, 49 or 54.4 percent of the patients had a Grade 3 or greater TEAE and 10 patients or 11.1% and in adverse events leading to study drug discontinuation. Of the 86 patients who received OBERDUO at 2 point 7 mgkg, 86 or 100 percent experienced a TEAE of any grade. 44 or 51.2 percent of patients had 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 a 2 mgkg dosing cohort, an acute myocardial infarction, which was not classified as treatment related.

Speaker 2

4 Grade 5 events occurred in the 2.7 mgkgdosing cohort, which included 1 cardiac arrest not classified as treatment related and 2 cases of pneumonitis, which are still being investigated initially assessed as possibly treatment related. In addition, a patient in a 2.7 mg per kg dosing cohort had a Grade 3 pleural effusion and subsequently died. In terms of specific treatment emergent adverse events, those with incidents greater than or equal to 10% are shown on Slide 15. For the 2 mgkg dosing cohort, the 5 most common TEAs of any grade in this dosing cohort included asthenia, nausea, peripheral edema, decreased appetite and fatigue. Of note, the incidence of pleural effusion in this cohort was Grade 1 of 8.9 percent and Grade 2 of 8.9%.

Speaker 2

There were no Grade 3 or greater events. Also, the incidence of palmar plantar erythrodysthesia syndrome in this cohort was a grade 1 of 11.1% and grade 2 of 4.4 percent. 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 edema, nausea and pleural effusion. Of note, the incidence of pleural effusion in this cohort was grade 1 of 14 point 0%, grade 2 of 14.0% and grade 3 of 1.2%.

Speaker 2

Also, the incidence of palmar plantar erythrodisesthesia syndrome in this cohort was 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 TAEs of greater than or equal to 10% 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 to 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 erythrocysthesia and pleural effusion in comparison as of the most recent data cut off to what we saw in the Phase 1 dose expansion study.

Speaker 2

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 or 2.7 mgs 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 Tamarac safety, efficacy and durability data, including RPFS in the second half of twenty twenty four 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 Tamarac 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-twenty 24.

Speaker 2

Recall that we have 2 other clinical molecules that target B7 H3. The first, MGC-twenty 6, is an investigational ADC incorporating a novel topoisomerase 1 inhibitor based linker payload, Syntycan E, which we licensed from Sinofix. Our second additional B7 H3 targeted molecule is enobasuzumab, an investigational Fc optimized monoclonal antibody. I'll walk you through both of these molecules next. MGC-twenty 6 incorporates a linker payload based on exotecan, a clinically validated and potent camtothecan that readily combines with Synafix's hydroSpace technology.

Speaker 2

MGC-twenty six preclinical data was presented recently at the American Association For Cancer Research Annual Meeting. In preclinical studies, MGC-twenty six was shown to have greater potency than B7 H3 directed antibodies conjugated to direxotecan or DXD, a topoisomerase based payload utilized in other ADCs. In addition, the MGC026 payload has been shown to be less susceptible to multidrug resistant mechanisms than DXD and SN38. Also a toxicology study conducted in cynomolgus monkeys showed that MGC-twenty 6 was well tolerated at all dose levels tested. Finally, MGC-twenty six displayed approximate dose proportional pharmacokinetics in the animal models tested, indicating predictable behavior conducive to further clinical development.

Speaker 2

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 VOBR Duo. We view MGC026 as a complementary approach to VOBRADUO for targeting B7 H3. More specifically, we believe that having distinct mechanisms of action, for VIRDUO 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.

Speaker 2

Regarding enoblituzumab, our academic collaborators are enrolling an investigator sponsored randomized translationally intense Phase 2 investigative sponsored study of this molecule in up to 2 19 patients with prostate cancer. The HEAT study is evaluating 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 immunoge, including CT and bone scan as well as PSMA PET and optional prostate MRI as per institutional preferences. Next, I'll update you on lorazirlimab, our bispecific tetravalent 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, which are most abundant in the tumor microenvironment.

Speaker 2

We are enrolling the LORAKEET study, a randomized Phase 2 clinical trial of loradrillumab 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. 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 lower key clinical data update in the first half of twenty twenty five. In addition, we continue to enroll patients in the Phase onetwo dose escalation study of VOBRADUO in combination with loradirlimab in patients with advanced solid tumors.

Speaker 2

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 CD123xCD3 DART molecule that incorporates a CD3 component designed to minimize cytokine release syndrome while maintaining antitumorcytolytic activity and permitting intermittent dosing through a longer half life. 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 is the option to license MGD-twenty four at predefined decision points during the Phase 1 study. In terms of preclinical projects, MGC-twenty eight is our 2nd topoisomerase 1 inhibitor based ADC incorporating Synafix's novel linker payload and an ADAM-nine targeting antibody.

Speaker 2

ADAM-nine is a member of the ADAM family of multifunctional type 1 transmembrane proteins that play a role in tumor genesis and cancer progression and is over expressed in multiple cancers, making it an attractive target for cancer treatment. We recently presented MGC-twenty eight preclinical data at the AACR Annual Meeting in April. In preclinical studies, MGC-twenty eight demonstrated specific antitumor activity in in vivo models representing gastric, lung, pancreatic, colorectal, small cell carcinoma of the head and neck and cholangiocarcinoma. In addition, in a non human primate study, MGC-twenty eight was well tolerated at high dose levels with mild reversible side effects and no ocular toxicity, which is often a concern Tubulin inhibitor based ADCs. These promising preclinical results support the continued investigation of MGC-twenty 8 as a therapeutic option for treating ADAM-nine expressing solid tumors.

Speaker 2

We are currently anticipating submitting an investigational new drug or IND application for MGC-twenty eight by the end of this year. Beyond MGC-twenty eight, we're 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.

Speaker 2

Operator?

Operator

Our first question comes from the line of Tara Bancroft with TD Cowen.

Speaker 3

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 2 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?

Speaker 3

And how this looks like quite different from the abstract with these just 2 more median cycles. So could you describe more what happened there?

Speaker 2

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 1st 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, third is if you look at the butterfly plot of the AEs, the side effects are overwhelmingly Grade 1 or 2 manageable with a smattering of Grade 3s, no concerning new type of side effects is 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.

Speaker 2

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 Tamarac and compared it to the prostate patients on the Phase 1 study also at 16 weeks. And the results in Tamarac are dramatically improved. For example, specifically, we had half the amount of Grade 3s in Tamarac as compared to the Phase 1 prostate group. One half to 1 third of the total of discontinuations and about half of the reductions in Tamarac as compared to the Phase 1 and only 1 third to 1 half of drug interruptions.

Speaker 2

So as we have laid out in terms of achieving this vis a vis the Phase 1 study, 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 the 2 mgs or the 15% of the 2.7 mgs. This compares well to a number of other studies. For example, in the CARD study cabozitaxel, there was a discontinuation rate of 19.8%.

Speaker 2

In KEYNOTE-nine twenty one, the docetaxel arm was 22.4% and similarly the combo arm with pembro was 29.2%. And then in TRITON3, for the dosing 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 3s, we can compare what we're seeing here, for instance, in the docetaxelam and TRITON3, 61%, KEYNOTE-nine twenty one, 36%. And then if you even look at experimental Phase 1 studies in prostate, some new targets, if you look at Amgen steep by CD3, it was 55% and in Daiichi, 7,300, it was 47% in their prostate.

Speaker 2

So all in all, again, as I've pointed out, while it the safety data has accumulated more safety side effects, we believe that these are extremely manageable. In 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.

Operator

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

Speaker 4

Hi, guys. Thanks for taking my questions. I guess I'm also just trying to better understand the evolution in the tolerability profile versus the previously submitted abstract. Is there a time dependency to the AEs? Or does this evolution reflect something else?

Speaker 4

And then second question, can you provide any additional color on the patient depth and whether or not they were treatment related? Thank you.

Speaker 2

Yes. Thanks so much for the point. So again, as I started off with a question from Tara, the cut off 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.

Speaker 2

And so as I said before, this 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, A, with other ADCs as well as other agents that have been approved in prostate cancer. So that's the summary there.

Speaker 2

With regard to the patient debts, as pointed out, a cardiac death and a cardiac arrest were not deemed to be associated with the drug unrelated. The additional cases, 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 cause and effect with regard to drug.

Speaker 2

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

Speaker 4

Got it. Thanks for taking my questions.

Operator

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

Speaker 5

Hi, guys. This is Ashik Mubarik on for Yigal. Thanks for taking my questions. A few from me. I guess on the grade 5 pneumonitis events, were you surprised that these occurred?

Speaker 5

I can't quite recall if pneumonitis had been observed as a signal previously. And to that end, is there B7 H3 expression in the lungs? And are you considering maybe integrating some type of steroid prophylaxis to help prevent pneumonitis moving forward?

Speaker 2

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 that's associated with the pneumonitis. With regard to Okay.

Speaker 2

Got it. And then And then 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.

Speaker 5

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.

Speaker 5

It seems like efficacy is balanced on PSA50, but ORRs are 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?

Speaker 2

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 mid year. 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.

Speaker 5

Got it. Thanks very much.

Operator

Our next question comes from the line of Kaveri Pullman with BTIG.

Speaker 6

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?

Speaker 2

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 experienced populations are under consideration for development if we go forward into the Phase 3 study. And nothing unexpected was observed with regard to either populations in terms of overall responses.

Speaker 6

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

Speaker 2

Well, again, as I we've shown very nicely and we wanted to illustrate that on the swimmers plots, these patients have sustained responses and continued even under circumstances when doses had been modified and reduced. As you looked on some of the longer treated patients, we had, as you saw on patient with 2.7 mg per kg and a patient on the 2 mg per kg 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 the responses so far as of the Syntyrem data.

Speaker 6

Got it. That's helpful. And maybe last one, any thoughts on why there is no correlation between efficacy and B7 H3 expression?

Speaker 2

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 is a threshold effect where you if you have a modest number of expression of B7H3 that's sufficient to provide entry of the toxin of the linker toxin into the cells. So we see that as actually as a positive result here. The caveat is, of course, these are archival specimens and there may be some differences if you do fresh biopsies.

Operator

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

Speaker 7

Yes, good afternoon. Thanks for taking 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 for 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 pneumonitis in the context of perhaps not proactively screening for?

Speaker 2

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 Disney, although again, the percentages are quite low. So again, I 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.

Speaker 2

So it's too early to draw any conclusions.

Speaker 7

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 arms at this point?

Speaker 2

It was the time we don't have included here and I don't know off the top of my head, but what we did is obviously you saw on the swimmer's plot the time and a large number of these significant number of these patients has exceeded the 16 to 20 week time interval. The number of doses, the median number of mean number of doses is now 5, so which is on a QA basis.

Speaker 7

And then just lastly, I know this trial allowed for patients who had not been on, I guess, stable ARPI for 12 months. Do you know how those patients attribute out between the two treatment arms with respect to patient baselines?

Speaker 2

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 ARAT exposure in that regard.

Speaker 5

Thanks for taking the questions.

Operator

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

Speaker 8

Hi guys. Thanks for taking my 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.

Speaker 8

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% and 56% on 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% in the 2.7 mg arm today. So when you look at the tox signals versus Phase 1, you 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 that you say, look, this is where it got better, this is where docs are going to be comfortable dosing this, This is the linchpin number that is going to let people stay on therapy longer than they did in Phase 1?

Speaker 2

Yes. So the again, I wanted 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 the comparison to the prostate cohort. I believe what you were pulling out is all different populations. So I'm 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're seeing at the same time interval around 16 weeks.

Speaker 2

So I'm trying to as best do an apples to apples comparison from a time exposure to drug. Now there could be some modest variations of what the ultimate drug exposure was, But I'm clearly seeing at least 2 to 3 times more of the side effect profiles and severity of grades in the Phase 1 prostate arm versus what we're seeing here in Tamarac. And so again, I will reiterate the feedback we're getting from the investigators has been manageable tolerability, not concerning. And in addition, as I pointed out earlier, we are now past where the mean number of doses in this Tamarac is visavis where we were in the Phase 1 study. And so I'm feeling very encouraged and that we are on the right pathway here for delivering this drug.

Speaker 2

And as I showed in the various swimmers plots, the majority of the patients are still on treatment despite some of the dose modifications and interruption.

Speaker 8

All right. I guess I understand that. Maybe on the efficacy side, I would love 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?

Speaker 2

So here as I pointed out, the entry criteria was no more than 3 lines of therapy. I don't know where it ended up on with regard to the median for this study, whether it was 2 or 3, but we'll 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 7,300 in their ESMO presentation was a solid 25% as well. The point I made was that we should certainly achieve the 25% by this end of the study.

Speaker 2

And as we see here, not only are we achieving it, it is likely we're 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 unconfirmed ORR ORR in the 2.7 mgkg of 43.8 percent. And in the 2.0 Q4 in the confirmed, unconfirmed, a 24.4%. So I think we're 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.

Speaker 8

All right. Makes sense. Can you talk about potential use of VOBERDUNA in combinations given the safety profile here? It's obviously not an innocuous molecule and some of the toxins are overlapping with other agents that you might expect to see in prostate space. So I'm thinking about pneumonitis and boa fusion for instance.

Speaker 8

So are you looking what does this mean for potential use in combination and thereby uses in earlier lines of therapy compared to other programs that are enthusiastically pursuing larger combinations in early line therapy?

Speaker 2

Well, again, we are very much interested in looking at combinations of VOBRADUO with different agents. And as you know, we have initiated dose finding studies with our lorazirlimab PD-one CTLA-four DARPA specific molecule. And as I commented earlier, we expect to be able to define the go forward doses from these dose finding studies very shortly, where we do not only look at this combination in prostate cancer, but in other tumors as well. And given that mechanistically, we believe these are very orthogonal mechanisms for controlling tumor. And as we have already shown, in addition to the VOBR DUE O data that we described today, activity independently as single agent of loradiromab in late stage patients, I think this will be a very good combination to explore and we are looking at the potential of others as well.

Speaker 2

All right. Thanks very much.

Operator

Our next question comes from the line of Etzer DeRout with BMO Capital Markets.

Speaker 9

Great. Thanks. Just wanted to know if you could provide a little bit more color around sort of the combination with specifically with loradrolumab, given that you had sort of indicated that you could move into sort of dose expansion studies with Vobra and loradrolumab the first half, I believe. Maybe you could comment on where you are with that program and is that still sort of a viable plan moving forward given the profile that we've seen today? Thanks.

Speaker 2

Yes. We are on track for moving forward with that. I think we're at the final evaluation of the dose finding cohort of finding, what the ideal doses of each one when put together to maximize both the safety and activity to explore. So I think we will be in a pretty good shape in the second half of the year to initiate enrollment in the prostate and potentially another tumor indication. So stay tuned for that.

Speaker 9

Thank you.

Operator

Our next question comes from Mayank Mamtami with B. Riley Securities.

Speaker 10

Good afternoon. Thanks for taking my question. So maybe on the look forward basis, Scott, if you could comment on your expectations for the RPFS data and how you may look to present that in the next few months based on what you're seeing on durability, median cycles? And I think importantly, how you see based on all that you know you see this fit in the paradigm relative to PSMHT1. C1?

Speaker 10

When you think about sequencing, you think about designing your Phase 3 next year?

Speaker 2

Yes. Thanks very much, Mayank. Right now, as I again laid out the parameters here as baseline, what we had indicated was an RPFS of at baseline of 6, but greater and obviously looking for 7, 8, 9, 10 or higher. I think that the data that we show today and the fact that these patients are still on therapy, I think we will ultimately see the results, but there is no reason we can't meet some of the longer lived RPFS values here. So we'll have to wait to the seeing the results.

Speaker 2

The expectation is that this would be presented at a scientific conference in the second half of this year.

Speaker 10

Got it. Thank you. And maybe just one quick clarification. There weren't too many RLT or prevertexposed patients in the study. Is that trying to do any kind of analysis, if you

Speaker 2

could clarify that? I'm sorry, did you say radiotherapy?

Speaker 10

Yes, RLT or taulectro exposed patients.

Speaker 2

That's true. And as you saw on the geographic distribution of the patients, there were a very a modest number of patients from the U. S. Where they would have the ability to when we initiated the study and when the enrollment occurred to either have seen Plavicto or have progressed on that given the timing of the marketing of that drug in the U. S.

Speaker 2

Versus Europe, where the majority of the patients came from Western Europe. So we expect small numbers of those patients in this study.

Speaker 10

Got it. Thanks for taking my question.

Operator

Our next question comes from the line of Silvan Turkan with Citizens JMP Securities.

Speaker 11

Yes, good afternoon and thanks for taking my question. First of all, when could we find out about the adjudication of the death if they are treatment related or not? Would that be available by the time we get that presentation at a medical conference in the second half?

Speaker 2

I would presume so. Obviously, we're giving you ongoing results as they come in. I mean, we're here in early May and as we just did this data cut in April. So the expectation is the teams are working very hard in finding out the details on the patient study and evaluating comorbidities and other things that may have contributed to the specific deaths.

Speaker 11

Great. But the DSMB is looking at these, right, presumably between

Speaker 2

January 1 and this data cut? Absolutely. Absolutely. Great.

Speaker 11

And then maybe talk to me maybe if you can walk me either through the waterfall plot or basically I'm trying to understand or reconcile the unconfirmed responses. There's a fair amount in the especially high in the high dose arm, where your confirmed response rate is 25%, but it could be with the unconfirmed as high as 43%. Are those responses the majority? Why from that? Are they still ongoing?

Speaker 11

Do they have patients in FS scanned yet? Or could you please characterize that?

Speaker 2

Well, yes. I mean, that's very if I look at the plots there of the swimmers plot, say, for the 2.7, the timing frequency with regard to the scans is every 8 weeks. And so again, if you look at the majority of these patients, if they were still on therapy as of 16 weeks would have had 2 scans, Those that had achieved 24 weeks would have had 3 scans. And there is at least one patient that probably had 4 scans. So for instance, if you look at the patient with 2.7 mg per kg Q4, the one on the top of that curve, they had initial evaluation for a PR that he achieved at 8 week, the first scan, but it wasn't until the probably the 4th scan that it was confirmed as a confirmed PR.

Speaker 2

So the bottom line is that it will take longer time. I mean there are a number of patients I see here that have one positive value and have not gotten the 2nd scan yet to confirm

Speaker 11

it. Great. Thanks for taking my questions.

Operator

Our next question comes from the line of Kelsey Goodwin with Guggenheim Partners.

Speaker 6

Hey, thanks for taking my question. I guess given the early looks at durability with the swimmer plot for the RECIST evaluable patients at least, I guess, do you have any update on how you're thinking about where durability may land for the fall update or just any additional color you could provide there? Thank you.

Speaker 2

Yes. I think it's just too early to say given that, again, the majority of the patients are still on, for example, the 2.7 mgs per kg in the patients with measurable disease, we have, as noted here on the slide, 62.5% that is still ongoing treatment. So again, we feel very encouraged that given even at this point that we should be able to have an opportunity to treat a large number of these patients with MCR PC.

Speaker 6

Got it. Thank you. And for the non RECIST evaluable patients, I guess, does the disease swimmer plots kind of are they representative for the non RECIST evaluable patients as well as this a representative look at it?

Speaker 2

Yes. Again, what we wanted to do is give you a representative feel for the various durability and we felt that this was a good representation with regard to resist evaluable with measurable disease at baseline. But I would say that our general view is that this can be extended to patients with bony disease as well, etcetera. So we're just we have this balance that we want to provide investors a look at this data as we had promised, but at the same time is having additional data that we can then present at scientific conferences. But nothing here is more selective in that regard.

Speaker 6

Got it. Okay. Thank you so much.

Operator

Our next question comes from the line of Peter Lawson with Barclays.

Speaker 12

Thank you. Thanks Scott for the update. Just wondering if you could possibly characterize what the spider plots look like and if these patients are staying on and the PSA50 reduction or PSA reductions improving over time or kind of the best way you could potentially characterize that?

Speaker 2

Yes. Again, what we try to do is give you a capsosarum, but I would say that the spider parts are exceptionally encouraging. As we had shown in the Phase 1 data, you will see initial reductions in PSAs and they seem to be sustained for long periods of time and in a time interval at least at this interim data going forward. Clearly, there are individual patients that will not have the continued PSA50 responses. But I would say, as we characterize the Phase 1, they do very well similarly over a long period of time.

Speaker 12

Got you. Thank you. And the PSA50 reduction was higher in that lower dose. Was that driven by a lower discontinuation rate or is there something else going on?

Speaker 2

I think this is just idiosyncratic. I would not over interpret these. Even though these are nice sized populations, I don't think there is anything particular. I would more look at the any I mean the fifty-fifty with regard to the patients that had at least one PSA50 reduction, I think says that both populations are seeing a similar even though the confirmed ones seem a little low on the 2.7. I think it's just spurious in that regard.

Speaker 2

And as I pointed out, is expecting that those numbers could potentially increase over time. So I don't look at that as a definitive parameter of the difference at this point.

Speaker 12

Got you. And then further question, whether the PSA reductions or if it's ORR or disease control rate, what correlates best in your mind for this agent and PFS?

Speaker 2

My sense, it's going to be our PFS and disease control rate. As I pointed out previously, avoiding new growth of lesions is the most important thing here. And so that obviously, if a patient has 30% or greater percent, it's recorded as a PR. But if a patient has 20% reduction, it will be recorded as a stable disease. As long as there are no new lesions, I think that is fine.

Speaker 2

But again, we'll have to see as the data continues to mature.

Speaker 12

Got you. Okay. Thank you so much.

Operator

That concludes today's question and answer session. I'd like to turn the call back to Doctor. Koenig for closing remarks.

Speaker 2

Well, thank you everybody for your questions today and we look forward to following up the completion of the Tamarac study and further updates on our other programs soon. Have a good evening.

Operator

This concludes today's conference call. Thank you for participating. You may now disconnect.

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BK Technologies Q1 2024
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