On May 9, 2024 Moleculin Biotech, Inc., (Nasdaq: MBRX) (Moleculin or the Company), a clinical stage pharmaceutical company with a broad portfolio of drug candidates targeting hard-to-treat tumors and viruses, reported it has received an Issue Notification from the United States Patent and Trademark Office (USPTO) for U.S. Patent number 11,980,634 titled, "Method of Reconstituting Liposomal Annamycin" (the ‘634 patent’) to be issued on May 14, 2024 to Moleculin and The University of Texas System Board of Regents (Press release, Moleculin, MAY 9, 2024, View Source [SID1234643006]).

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When issued, the patent will provide claims to liposomal Annamycin suspension compositions with a base patent term currently extending until June 2040, subject to extension to account for time required to fulfill regulatory requirements for FDA approval. Moleculin’s novel candidate for the treatment of acute myeloid leukemia (AML) and soft tissue sarcoma lung metastases (STS lung mets) uses a unique lipid-based delivery technology. In addition to the expected ‘634 patent and recently issued ‘118 patent, Moleculin has additional patent applications related to Annamycin pending in the U.S. and in major jurisdictions worldwide.

Walter Klemp, CEO and Chairman of Moleculin, stated, "We remain committed to establishing a robust patent estate for Annamycin and driving its development forward. In addition to our recently announced composition of matter patent for Annamycin, we believe we are well positioned for the potential partnering discussions which we expect to have in the near future. The issuance of this patent further underscores the importance and proprietary nature of the innovation that makes this next generation anthracycline possible and bolsters our confidence in its potential to address a number of high-value indications where there remains unmet medical need."

Annamycin is the Company’s next-generation anthracycline that has been designed to be non-cardiotoxic (unlike currently prescribed anthracyclines) and has shown to be non-cardiotoxic in the 82 subjects treated in multiple studies in the U.S. and in Europe. Furthermore, Annamycin has recently shown in Moleculin’s European clinical study for the treatment of AML using Annamycin in combination with Cytarabine (MB-106) a preliminary 60% composite complete response (CRc) rate in 2nd line subjects (N=10) and an overall interim CRc of 39% in all subjects (N=18), regardless of the prior number of therapies, in the European trial. Durability of the CRc’s is developing. One subject has surpassed the one-year mark with a durable complete response. Recruitment in MB-106 has ended for 2nd line subjects while recruitment for 1st line and 3rd line subjects continue. Annamycin is currently in development for the treatment for AML and STS lung mets, and the Company believes the drug may have the potential to treat additional indications.

Disclosure
MD Anderson has an institutional conflict of interest with Moleculin, and this relationship is managed according to an MD Anderson Institutional Conflict of Interest Management and Monitoring Plan.

On May 9, 2024 Mersana Therapeutics, Inc. (NASDAQ: MRSN), a clinical-stage biopharmaceutical company focused on discovering and developing a pipeline of antibody-drug conjugates (ADCs) targeting cancers in areas of high unmet medical need, reported a business update and announced financial results for the first quarter ended March 31, 2024 (Press release, Mersana Therapeutics, MAY 9, 2024, View Source [SID1234643005]).

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"In recent months, we presented new preclinical and clinical Dolasynthen data demonstrating our next-generation cytotoxic ADC platform’s potential to reduce adverse events that limit other ADC platforms," said Martin Huber, M.D., President and Chief Executive Officer of Mersana Therapeutics. "Given this emerging platform profile and the objective responses we have seen to date with XMT-1660, we are continuing to advance Phase 1 dose escalation and backfill cohorts in parallel to optimize our dose, schedule and biomarker prior to initiating expansion. Additionally, we are pleased to have resumed patient recruitment in our Phase 1 clinical trial of XMT-2056 and look forward to advancing dose escalation this year."

Recent Accomplishments, Strategic Priorities and Expected Milestones

XMT-1660: Mersana continues to advance its Phase 1 clinical trial of XMT-1660, the company’s lead Dolasynthen ADC candidate targeting B7-H4. The dose escalation portion of the trial is ongoing, a maximum tolerated dose has yet to be established and enrollment of patients in backfill cohorts to optimize dose and schedule continues. Mersana plans to share initial dose escalation and backfill cohort data and initiate the expansion portion of the trial in the second half of 2024.

XMT-2056: In the first quarter of 2024, Mersana reopened clinical sites and resumed patient recruitment for its Phase 1 clinical trial of XMT-2056, the company’s lead Immunosynthen ADC candidate targeting a novel HER2 epitope, following the lifting of a clinical hold on the trial in the fourth quarter of 2023. The company plans to advance dose escalation in this trial in 2024. GSK plc has an exclusive global license option to co-develop and commercialize XMT-2056.

Collaborations: Mersana continues to advance its Johnson & Johnson and Merck KGaA, Darmstadt, Germany collaborations. The Johnson & Johnson collaboration and license agreement focuses on the discovery of novel Dolasynthen ADCs for up to three targets. The Merck KGaA, Darmstadt, Germany collaboration and license agreement focuses on the discovery of novel Immunosynthen ADCs for up to two targets.

Dolasynthen Platform Differentiation: At the European Society of Gynaecological Oncology (ESGO) 2024 Congress in March 2024 and the American Association for Cancer Research (AACR) (Free AACR Whitepaper) 2024 Annual Meeting in April 2024, preclinical and clinical data were presented demonstrating a reduction in presumed off-target platform toxicities with an ADC developed utilizing Dolasynthen, the company’s next-generation platform, compared with one developed using the company’s first-generation platform.

First Quarter 2024 Financial Results

Cash, cash equivalents and marketable securities as of March 31, 2024 were $183.1 million. Mersana continues to expect that its capital resources will be sufficient to support its current operating plan commitments into 2026.
Net cash used in operating activities for the first quarter of 2024 was $32.7 million.
Collaboration revenue for the first quarter of 2024 was $9.2 million, compared to $7.8 million for the same period in 2023. The year-over-year change was primarily related to the company’s Johnson & Johnson collaboration, including both research and CMC activities.
Research and development (R&D) expenses for the first quarter of 2024 were $18.7 million, compared to $47.3 million for the same period in 2023. Included in the first quarter of 2024 R&D expenses were $2.5 million in non-cash stock-based compensation expenses. The year-over-year decline in R&D expenses was primarily related to reduced costs associated with manufacturing and clinical activities for UpRi and reduced employee compensation following the restructuring announced by the company in July 2023.
General and administrative (G&A) expenses for the first quarter of 2024 were $11.6 million, compared to $18.3 million during the same period in 2023. Included in the first quarter of 2024 G&A expenses were $2.1 million in non-cash stock-based compensation expenses. The year-over-year decline in G&A expenses was primarily related to reduced consulting and professional services fees and reduced employee compensation expense following the aforementioned restructuring.
Net loss for the first quarter of 2024 was $19.3 million, or $0.16 per share, compared to a net loss of $56.2 million, or $0.52 per share, for the same period in 2023.
Conference Call Reminder
Mersana will host a conference call today at 8:00 a.m. ET to discuss business updates and its financial results for the first quarter of 2024. To access the call, please dial 833-255-2826 (domestic) or 412-317-0689 (international). A live webcast of the presentation will be available on the Investors & Media section of the Mersana website at www.mersana.com, and a replay of the webcast will be available in the same location following the conference call for approximately 90 days.

On May 9, 2024 Merck (NYSE: MRK), known as MSD outside of the United States and Canada, reported that the Phase 3 KEYNOTE-B21 trial evaluating KEYTRUDA, Merck’s anti-PD-1 therapy, in combination with chemotherapy as adjuvant treatment, with or without radiotherapy, did not meet its primary endpoint of disease-free survival (DFS) for the treatment of patients with newly diagnosed, high-risk endometrial cancer after surgery with curative intent (Press release, Merck & Co, MAY 9, 2024, View Source [SID1234643004]).

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At a pre-specified interim analysis conducted by an independent Data Monitoring Committee, adjuvant treatment with KEYTRUDA plus chemotherapy, with or without radiotherapy, did not meet the study’s pre-specified statistical criteria for DFS compared to placebo plus adjuvant chemotherapy, with or without radiotherapy. The study’s other primary endpoint of overall survival (OS) was not formally tested since superiority was not reached for DFS. The safety profile of KEYTRUDA was consistent with that observed in previously reported studies; no new safety signals were identified. A full evaluation of the data from this study is ongoing. Merck will work with investigators to share the results with the scientific community.

"While these results were not what we had hoped, we are focused on continuing to build on the established role of KEYTRUDA in advanced endometrial carcinoma through our approved indications, while rapidly progressing clinical research evaluating KEYTRUDA-based combinations and other investigational candidates, including antibody-drug conjugates, in endometrial and other types of gynecologic malignancies," said Dr. Gursel Aktan, vice president, global clinical development, Merck Research Laboratories. "We would like to thank all the patients, the investigators and our study collaborators for their participation in this trial."

In the U.S., KEYTRUDA has two approved indications in endometrial cancer. One indication, based on KEYNOTE-775/Study 309, is in combination with LENVIMA (lenvatinib), in collaboration with Eisai, for the treatment of patients with advanced endometrial carcinoma that is mismatch repair proficient (pMMR), as determined by an FDA-approved test, or not microsatellite instability-high (MSI-H), who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation. The second indication, based on KEYNOTE-158, is as a single agent, for the treatment of patients with advanced endometrial carcinoma that is MSI-H or mismatch repair deficient (dMMR), as determined by an FDA-approved test, who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation.

Merck has a comprehensive clinical development program in endometrial carcinoma, including the NRG-GY018/KEYNOTE-868 trial evaluating KEYTRUDA in combination with standard of care chemotherapy (carboplatin and paclitaxel), followed by KEYTRUDA as a single agent for the treatment of patients with primary advanced or recurrent endometrial carcinoma. As previously announced, the U.S. Food and Drug Administration (FDA) has granted priority review for Merck’s supplemental Biologics License Application (sBLA) based on this study and has set a Prescription Drug User Fee Act (PDUFA), or target action, date of June 21, 2024.

The program also includes the KEYNOTE-C93 study evaluating KEYTRUDA versus chemotherapy in dMMR advanced or recurrent endometrial carcinoma, as well as the MK-2870-005 study evaluating sacituzumab tirumotecan (sac-TMT), an investigational trophoblast cell-surface antigen 2 (TROP2)-directed antibody-drug conjugate (ADC) being developed in collaboration with Kelun-Biotech, compared to a treatment of physicians’ choice in patients with endometrial carcinoma who have received prior platinum-based chemotherapy and immunotherapy.

About KEYNOTE-B21/ENGOT-en11/GOG-3053
KEYNOTE-B21, also known as ENGOT-en11/GOG-3053, is a randomized, double-blind Phase 3 trial (ClinicalTrials.gov, NCT04634877) sponsored by Merck and conducted in collaboration with the European Network for Gynecologic Oncology Trial (ENGOT) groups and the GOG Foundation, Inc. (GOG) investigating adjuvant treatment with KEYTRUDA plus chemotherapy, with or without radiotherapy, compared to adjuvant placebo plus chemotherapy, with or without radiotherapy, for the treatment of newly diagnosed, high-risk endometrial cancer after surgery with curative intent. The primary endpoints are DFS and OS, and secondary endpoints include safety. The trial enrolled an estimated 1,095 patients who were randomized to receive:

KEYTRUDA (200 mg every three weeks for six cycles) plus concurrent standard of care chemotherapy (for four or six cycles), followed by KEYTRUDA (400 mg every six weeks for an additional six cycles), with or without radiotherapy, or
Placebo (every three weeks for six cycles) plus concurrent standard of care chemotherapy (for four or six cycles), followed by placebo (every six weeks for an additional six cycles), with or without radiotherapy.
About endometrial carcinoma
Endometrial carcinoma begins in the inner lining of the uterus, which is known as the endometrium, and is the most common type of cancer in the uterus. In the U.S., it is estimated there will be approximately 67,880 patients diagnosed with uterine body cancer and approximately 13,250 patient deaths from the disease in 2024. Globally, endometrial cancer is the sixth most common cancer in women and the 15th most common cancer overall. Following primary treatment, patients face a risk of their cancer returning, often as distant metastasis, which is associated with poorer outcomes.

On May 9, 2024 MEI Pharma, Inc. (Nasdaq: MEIP), a clinical-stage pharmaceutical company evaluating novel drug candidates to address known resistance mechanisms to standard-of-care cancer therapies, reported results for the three and nine months ended March 31, 2024, and highlighted recent corporate events (Press release, MEI Pharma, MAY 9, 2024, View Source [SID1234643003]).

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"Over the past several months, MEI has received encouraging clinical data for voruciclib and ME-344 supporting the further development of these programs," said David Urso, president and chief executive officer of MEI Pharma. "The clinical focus for the rest of the year will be voruciclib, our oral CDK9 inhibitor. We anticipate providing updates from the clinical trial evaluating voruciclib in combination with venetoclax in patients with relapsed/refractory AML, a study designed to provide additional evidence of the anti-leukemic activity of this combination, during the remainder of calendar 2024."

Mr. Urso continued: "While venetoclax is an established option for patients with AML and is increasingly used as a standard treatment, the disease typically progresses and patients require therapy after venetoclax, which consistently yields limited benefit. While treatments targeting specific patient populations with mutations such as FLT3 and IDH and the menin inhibitors may be an option for some relapsed/refractory AML patients, the majority of patients do not have therapeutically actionable mutations. We believe that voruciclib in combination with venetoclax has potential, as a mutation-agnostic therapy, to benefit the largest number of patients with relapsed/refractory AML."

Select Third Quarter Fiscal Year 2024 and Recent Highlights

•
In January 2024, MEI presented a Trials in Progress poster of the Phase 1b study of ME-344, an investigational inhibitor of mitochondrial oxidative phosphorylation ("OXPHOS"), evaluating the combination with bevacizumab (Avastin) in refractory metastatic colorectal cancer patients at the 2024 ASCO (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium.

•
In March 2024, the MEI reported initiation of enrollment in an expansion cohort in the ongoing Phase 1 study evaluating voruciclib, its investigational selective oral cyclin-dependent kinase 9 ("CDK9") inhibitor, in combination with venetoclax (Venclexta), a B-cell lymphoma 2 ("BCL2") inhibitor, in relapsed and refractory ("R/R") acute myeloid leukemia ("AML") patients. The decision to open the expansion cohort was based on initial data demonstrating anti-leukemic activity, including complete responses in heavily pretreated patients. Additionally, at doses of 100 mg or more, initial results from correlative biomarker assay analyses of available samples from patients treated with the combination demonstrated anticipated decreases of myeloid leukemia cell differentiation protein ("Mcl-1"), including progressively greater decreases in Mcl-1 in patients achieving a response compared to patients with stable disease or progressive disease. We also observed expected increases in Mcl-1 after administering venetoclax and subsequent anticipated decreases in Mcl-1 after administering voruciclib, supporting our hypothesis that voruciclib, as an inhibitor of CDK9, regulates Mcl-1 and therefore may address the increase of Mcl-1 levels associated with venetoclax. There was no evidence of overlapping toxicity with venetoclax and no dose limiting toxicities were observed.

•
In April 2024, MEI reported that 25% of evaluable patients with relapsed metastatic colorectal cancer in Cohort 1 of the Phase 1b study evaluating ME-344, an investigational inhibitor of mitochondrial oxidative phosphorylation, in combination with bevacizumab (Avastin) had no disease progression at Week 16. This landmark analysis exceeded the 20% threshold set in the Clinical Study Protocol to add an additional 20 patients to the study via the initiation of Cohort 2. The combination was also observed to be generally well-tolerated to date. While the threshold was met to proceed to Cohort 2, following a strategic review the Company decided to continue to advance ME-344 via its ongoing development of a new formulation rather than through the addition of a new cohort of patients. The Company has already initiated research and development activity of the new formulation with the goal of increasing biological activity, improving convenience of administration and increasing the commercial opportunity.

•
In April 2024, MEI reported that its Board of Directors unanimously aligned on a strategy to prioritize clinical development of voruciclib and enable development of a new ME-344 formulation for the potential of a future Phase 1 study. Additionally, the Company’s Board of Directors unanimously determined not to proceed with a second return of capital under the October 31, 2023, Anson Funds and Cable Car Capital cooperation agreement in order to conserve resources and align strategic investment, and thereby extend the Company’s operational cash runway.

Expected Drug Candidate Pipeline Developments

Voruciclib – Oral CDK9 inhibitor in Phase 1 Study

•
MEI expects to report clinical data from additional dose escalation and expansion cohorts of the ongoing Phase 1 clinical trial evaluating voruciclib plus venetoclax in patients with R/R AML during the remainder of calendar 2024.

The Company has completed patient enrollment of the dose expansion cohort evaluating a 300 mg dose of voruciclib administered daily for 14 consecutive days in a 28-day cycle in combination with standard dose venetoclax. Additionally, MEI is enrolling dose escalation cohorts evaluating up to four dose levels of voruciclib starting at 150 mg administered daily for 21 consecutive days in a 28-day cycle in combination with venetoclax.

ME-344 –Inhibitor of Mitochondrial OXPHOS in Phase 1b Study

•
MEI has initiated research and development activity of a new ME-344 formulation with the goal of increasing biological activity, improving convenience of administration and increasing the commercial opportunity. The Company expects to provide an update on our formulation efforts in the first half of calendar 2025.

Select Third Quarter and Nine Months Financial Results for Fiscal Year 2024

•
As of March 31, 2024, MEI had $56.6 million in cash, cash equivalents, and short-term investments with no outstanding debt.

•
For the nine months ended March 31, 2024, cash used in operations was $32.5 million, compared to $41.2 million during the nine months ended March 31, 2023. The decrease is primarily due to the timing of payments on operating liabilities, as compared to the prior period combined with a lower clinical spend due to the wind down of the zandelisib program resulting from the discontinuation of development activities announced in December 2022.

•
Research and development expenses decreased by $9.9 million to $5.2 million for the quarter ended March 31, 2024, compared to $15.1 million for the quarter ended March 31, 2023. The decrease was primarily related to a reduction in zandelisib program costs, as well as reduced personnel and related costs from our reductions in headcount. These decreases were partially offset by increases related to clinical trials, reformulation and manufacturing costs associated with ME-344 and increased clinical costs for the ongoing clinical study with voruciclib.

•
General and administrative expenses decreased by $2.6 million to $4.6 million for the quarter ended March 31, 2024, compared to $7.2 million for the quarter ended March 31, 2023. The decrease was primarily related to reduced personnel and related costs from our reductions in headcount, as well as lower external legal expenses.

•
MEI recognized no revenue for the quarter ended March 31, 2024, compared to $5.9 million for the quarter ended March 31, 2023. The decrease in revenue was due to all remaining noncash deferred revenue associated with the Kyowa Kirin Commercialization Agreement having been recognized in the first quarter of fiscal year 2024 due to the termination of that agreement in July 2023.

The Company believes its cash balance is sufficient to fund operations for at least the next 12 months.

On May 9, 2024 MacroGenics, Inc. (NASDAQ: MGNX), a biopharmaceutical company focused on discovering, developing, manufacturing and commercializing innovative antibody-based therapeutics for the treatment of cancer, reported an update on its recent corporate progress and announced financial results for the quarter ended March 31, 2024 (Press release, MacroGenics, MAY 9, 2024, View Source [SID1234643002]).

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"We are very encouraged by the interim updated safety and preliminary efficacy data from the TAMARACK study of vobra duo in metastatic castration-resistant prostate cancer," said Scott Koenig, M.D., Ph.D., President and CEO of MacroGenics. "We believe this interim data set helps validate our previously stated hypothesis that improved tolerability coupled with compelling biological activity could be achieved through dose reductions and a longer dosing interval. We believe vobra duo’s biological activity shown to date aligns well with the parameters we outlined at the outset of the study. Based on our evaluation of the interim data to date, we have initiated planning activities for a potential Phase 3 study that could commence next year. We anticipate sharing final safety, efficacy and durability data, including radiographic progression-free survival data, which is the primary endpoint of the study, in the second half of 2024. Furthermore, having preliminarily identified suitable vobra duo doses in mCRPC in the TAMARACK study, we have greater confidence in the molecule’s potential to help patients with a broad range of B7-H3-expressing cancers."

"The interim safety and anti-tumor activity observed to date in the TAMARACK study look very promising for patients with metastatic castration-resistant prostate cancer," said Johann DeBono, Regius Professor of Cancer Research and Professor in Experimental Cancer Medicine at The Institute of Cancer Research, London and The Royal Marsden NHS Foundation Trust. "With the limited treatment options currently available to these patients, this novel ADC molecule could potentially become the first therapy targeting B7-H3 in patients with prostate cancer and would represent an important new treatment for this population."

Updates on Proprietary Investigational Programs

Recent progress and anticipated events related to MacroGenics’ investigational product candidates are highlighted below.

B7-H3-Directed Therapies

• Vobramitamab duocarmazine (vobra duo) is an antibody-drug conjugate (ADC) that targets B7-H3, an antigen with broad expression across multiple solid tumors and a member of the B7 family of molecules involved in immune regulation.

• MacroGenics completed enrollment of the TAMARACK Phase 2 study of vobra duo in November 2023. TAMARACK is being conducted in patients with metastatic castration-resistant prostate cancer (mCRPC) who were previously treated with one prior androgen receptor axis-targeted therapy (ARAT). Participants may have received up to one prior taxane-containing regimen, but no other chemotherapy agents. The TAMARACK study is designed to evaluate vobra duo at two different doses: 2.0 mg/kg or 2.7 mg/kg every four weeks (q4W).

• A new presentation of TAMARACK interim data, consisting of updated safety and preliminary efficacy data, all based on a data cut-off date of April 12, 2024, is available under "Events & Presentations" in the Investor Relations section of MacroGenics’ website or directly via this link. Below is a high-level summary of this interim data, which is subject to further updates:

Vobra Duo
2.0 mg/kg q4W Vobra Duo
2.7 mg/kg q4W
Patients Enrolled n=91 n=90
PSA Reduction Summary:
PSA Evaluable Patients n=82 n=71
Any PSA Reduction ≥50% 41 (50.0%) 36 (50.7%)
Confirmed PSA Reduction ≥50% 36 (43.9%) 26 (36.6%)
Tumor Response Summary:
RECIST Evaluable Patients with Measurable Disease at Baseline n=45 n=32
Disease Control Rate (CR+PR+SD) 41 (91.1%) 28 (87.5%)
Overall Response Rate (CR+PR, confirmed only) 8 (17.8%) 8 (25.0%)
Overall Response Rate (CR+PR, including unconfirmed) 11 (24.4%) 14 (43.8%)
Safety Summary:
Safety Population n=90 n=86
Treatment-Emergent Adverse Events All Grade 89 (98.9%) 86 (100.0%)
Treatment- Emergent Adverse Events Grade ≥3 49 (54.4%) 44 (51.2%)
TEAE Leading to Study Drug Discontinuation 10 (11.1%) 13 (15.1%)
TEAE Leading to Study Drug Dose Reduction 39 (43.3%) 44 (51.2%)
TEAE Leading to Study Drug Dose Interruption 38 (42.2%) 48 (55.8%)
Five Most Common TEAE All Grade Asthenia (46.7%)
Nausea (35.6%)
Oedema peripheral (32.2%) Decreased appetite (28.9%) Fatigue (25.6%) Asthenia (58.1%)
Decreased appetite (37.2%) Oedema peripheral (36.0%) Nausea (30.2%)
Pleural effusion (29.1%)
Pleural Effusions Grade 1=8.9%
Grade 2=8.9%
No Grade ≥ 3 event Grade 1=14.0%
Grade 2=14.0%
Grade 3=1.2%
Palmar-plantar Erythrodysaesthesia Syndrome Grade 1=11.1%
Grade 2=4.4%
No Grade ≥ 3 event Grade 1=12.8%
Grade 2=9.3%
Grade 3=1.2%

• The median number of cycles of vobra duo administered was five (range of 1-10).

• A total of five events with fatal outcome occurred as follows: one Grade 5 event in the 2.0 mg/kg dosing cohort: acute myocardial infarction (considered unrelated to study drug by the investigator); three Grade 5 events in the 2.7 mg/kg dosing cohort: one cardiac arrest (considered unrelated to study drug by the investigator) and two events of pneumonitis. In addition, a patient in the 2.7 mg/kg dosing cohort had a Grade 3 pleural effusion that is recorded as having a fatal outcome. The latter three deaths are being investigated, as follow-up is incomplete on this ongoing trial.

• Additional data is provided in the presentation on the Company’s website and as filed with the Securities and Exchange Commission.

• Based on a current evaluation of this interim data, the Company is undertaking the initial steps necessary to prepare for the potential initiation of a Phase 3 study in mCRPC in 2025. The final decision to pursue such a Phase 3 study will be based on an analysis of the final data set, including rPFS, when available.

• The Company intends to share final safety, efficacy, and durability data, including the primary endpoint of radiographic progression-free survival, from the TAMARACK trial in the second half of 2024.

• MacroGenics plans to expand the TAMARACK study of vobra duo by enrolling patients with non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), melanoma, squamous cell carcinoma of the head and neck (SCCHN) and anal cancer. The Company expects to initiate dosing in these additional cohorts in mid-2024.

• MacroGenics continues to enroll a Phase 1/2 dose escalation study of vobra duo in combination with lorigerlimab in patients with various advanced solid tumors. The Company anticipates commencing a dose expansion study of this combination in mCRPC and at least one additional indication in 2024.

• MGC026 is a clinical B7-H3-targeting ADC that is site-specifically conjugated to exatecan, a topoisomerase I inhibitor payload developed by Synaffix (a Lonza company). With distinct mechanisms of action, vobra duo and MGC026 may address different cancers, tumor stages, or be used in combination with alternate agents — or potentially with one another — to enhance their clinical utility. A Phase 1 dose escalation study of MGC026 in patients with advanced solid tumors is ongoing.

MGC026 preclinical data was presented recently at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting. In preclinical studies, MGC026 was shown to have greater potency than B7-H3-directed antibodies conjugated to deruxtecan, or DXd, a topoisomerase-based payload utilized in other ADCs. In addition, the MGC026 payload has been shown to be less susceptible to multi-drug resistance (MDR) mechanisms than DXd and SN-38.

• Enoblituzumab is an Fc-optimized monoclonal antibody that targets B7-H3. The HEAT study, an investigator-sponsored, randomized Phase 2 clinical trial being conducted by MacroGenics’ academic collaborators, is ongoing. This study is being conducted to evaluate the activity of neoadjuvant enoblituzumab given prior to radical prostatectomy in up to 219 men with high-risk localized prostate cancer.

Lorigerlimab

• Lorigerlimab is a bispecific, tetravalent PD-1 × CTLA-4 DART molecule. In addition to the ongoing study of lorigerlimab in combination with vobra duo mentioned above, MacroGenics is enrolling LORIKEET, a randomized Phase 2 study of lorigerlimab in combination with docetaxel vs. docetaxel alone in second-line, chemotherapy-naïve mCRPC patients. A total of 150 patients are planned to be treated in the 2:1 randomized study. The current trial design includes a primary study endpoint of radiographic progression-free survival (rPFS). The Company anticipates completing enrollment of the study in 2024 and providing a clinical update in the first half of 2025.

Emerging ADC Pipeline

• MGC028 is a preclinical ADC incorporating an ADAM9-targeting antibody and represents the second MacroGenics ADC molecule that incorporates Synaffix’s novel site-specific linker and topoisomerase I inhibitor-based cytotoxic payload. ADAM9 (a disintegrin and metalloprotease domain 9) is a member of the ADAM family of multifunctional type 1 transmembrane proteins that play a role in tumorigenesis and cancer progression and is overexpressed in multiple cancers, making it an attractive target for cancer treatment. The Company currently anticipates submitting an investigational new drug (IND) application for MGC028 by the end of 2024.

MGC028 preclinical data was presented recently at the AACR (Free AACR Whitepaper) Annual Meeting. In preclinical studies, MGC028 demonstrated specific antitumor activity in in vivo models representing gastric, lung, pancreatic, colorectal cancer, SCCHN 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 often a concern with tubulin-inhibitor-based ADCs. These promising preclinical results support the continued investigation of MGC028 as a therapeutic option for treating ADAM9-expressing solid cancers.

Partnered Program

• MGD024 is a next-generation, humanized CD123 × CD3 DART molecule designed to minimize cytokine-release syndrome, while maintaining anti-tumor cytolytic activity, and permitting intermittent dosing. MacroGenics continues to enroll patients in a Phase 1 dose-escalation study of MGD024 in patients with CD123-positive neoplasms, including acute myeloid leukemia and myelodysplastic syndromes. Under an October 2022 exclusive option and collaboration agreement, Gilead Sciences, Inc. has the option to license MGD024 at predefined decision points during the Phase 1 study.

First Quarter 2024 Financial Results

• Cash Position: 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.

• Revenue: 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. The decrease was primarily due to a decrease in revenue from collaborative and other agreements, including a $15.0 million milestone received from Incyte in the quarter ended March 31, 2023.

• R&D Expenses: Research and development expenses were $46.0 million for the quarter ended March 31, 2024, compared to $45.9 million for the quarter ended March 31, 2023.

• SG&A Expenses: 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 other professional fees.

• Net Loss: Net loss was $52.2 million for the quarter ended March 31, 2024, compared to net loss of $38.0 million for the quarter ended March 31, 2023.

• Shares Outstanding: Shares of common stock outstanding as of March 31, 2024 were 62,560,502.

• Cash Runway Guidance: MacroGenics anticipates that its cash, cash equivalents and marketable securities balance of $184.2 million as of March 31, 2024, in addition to projected and anticipated future payments from partners and product revenues should extend its cash runway into 2026. The Company’s expected funding requirements reflect anticipated expenditures related to the Phase 2 TAMARACK clinical trial, the Phase 2 LORIKEET study as well as MacroGenics’ other ongoing clinical and preclinical studies.

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