Scott Koenig
Analyst · Guggenheim Securities. Your line is open
Thank you, Jim. We continue to believe our proprietary pipeline of product candidates has great promise. And I will walk you through each of our key programs momentarily as well as tell you about our plans for upcoming clinical programs. But before I do that, let me quickly remind you that since mid-2022, through our business development efforts as well as milestone achievements, we have received $335 million of non-dilutive capital. This includes $215 million from Provention, DRI, Sanofi in connection with TZIELD, $75 million from Gilead and $45 million from Incyte in connection with ZYNYZ. Vobramitamab duocarmazine or vobra duo is our ADC designed to deliver a DNA-alkylating duocarmycin cytotoxic payload to tumors expressing B7-H3. B7-H3 is a member of the B7 family of molecules involved in immune regulation. vobra duo was designed to take advantage of this antigen’s broad expression across multiple solid tumor types. We began enrolling the TAMARACK Phase 2 study of vobra duo under a modified study protocol during the second quarter. I am thrilled to tell you that we recently completed enrollment of this study ahead of schedule. As a reminder, TAMARACK is being conducted in patients with metastatic castration-resistant prostate cancer, or mCRPC, who have previously treated with one prior antigen receptor access targeted therapy. Participants may have received up to one prior taxing containing regimen but no other chemotherapy agent. This study is being conducted to evaluate vobra duo in patients across 2 experimental arms of either 2 mgs/per kg or 2.7 mgs/per kg every 4 weeks. We anticipate having data from the study to share with you in the first half of 2024. Next, I will update you on Lorigerlimab, our bispecific, tetravalent PD-1 x CTLA-4 DART molecule. We designed lorigerlimab to have preferential blockade on dual PD-1 CTLA-4 expressing cells, such as tumor infiltrating lymphocytes or TILs, which are most abundant in the tumor microenvironment. We recently began enrolling the LORIKEET study of randomized Phase 2 clinical trial of lorigerlimab in combination with docetaxel vs. 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 a primary study endpoint of radiographic progression-free survival or rPFS. Given that we just commenced enrollment, we’ll need more time to estimate when we might complete enrollment and have data to share from the study. 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, including renal cell carcinoma, pancreatic cancer, ovarian cancer, hepatocellular carcinoma, mCRPC and melanoma. We anticipate commencing the dose expansion portion of the study in 2024. Next up, MGD024 is our next-generation, bispecific CD123 CD3 DART molecule that incorporates CD3 component designed to minimize cytokine-release syndrome, while maintaining anti-tumor 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 at predefined decision points during the Phase 1 study. Also, as part of our collaboration with Gilead and as Jim already mentioned, we received a $15.7 million milestone from Gilead related to their nomination of the first of 2 potential research programs that leverage our DART and TRIDENT platforms for bispecific antibody. This nomination grants Gilead an exclusive option upon achievement of a predefined preclinical milestone to license worldwide rights to this first research program. MacroGenics will conduct the work related to this program on behalf of and funded by Gilead. Next, enoblituzumab is an Fc-optimized monoclonal antibody that targets B7-H3. Recently published data from a Phase 2 investigator-sponsored study of enoblituzumab in men with prostate cancer prompted our academic collaborators to initiate an investigator-sponsored randomized translationally intense prostate cancer clinical trial. The HEAT study is expected to commence enrollment in early 2024. And we’ll evaluate the activity of neoadjuvant enoblituzumab, given prior to radical prostatectomy in men with high-risk localized prostate cancer. Eligible patients will undergo a pre-treatment prostate biopsy and conventional imaging CT and bone scan as well as PSMA PET and optional prostate MRI as per institutional preferences. Finally, on our second quarter earnings call, I described our ongoing efforts in developing preclinical ADC molecules utilizing linker payload technologies we licensed from Synaffix. I’m very pleased to tell you we recently submitted an investigational new drug or IND application to the U.S. FDA for the first of these ADCs MGC026. This molecule utilizes a topoisomerase inhibitor based cytotoxic mechanism directed against an undisclosed solid tumor target. In preclinical studies, the activity of this linker toxin combination compared very favorably with that of other topoisomerase inhibitor-based ADC technology. We look forward to sharing the preclinical data with you at a future scientific conference and telling you more about this molecule in early 2024. In addition to MGC026, we are readying a second topoisomerase inhibitor-based ADC for which we currently expect to submit an IND in late 2024. And behind these 2 ADCs, we are exploring additional molecules for potential future IND submission. Stay tuned. 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. Operator?