MacroGenics Reports Q1 2024 Results and TAMARACK Study Update

MacroGenics, Inc., a biopharmaceutical firm specializing in innovative antibody-based treatments for cancer, recently provided corporate updates and financial results for the first quarter ending March 31, 2024. In a notable progress announcement, the company shared interim safety and preliminary efficacy data from its Phase 2 TAMARACK study, evaluating vobra duo in patients with metastatic castration-resistant prostate cancer (mCRPC).

Scott Koenig, President and CEO of MacroGenics, expressed optimism about the interim data, highlighting that the findings support their hypothesis regarding improved tolerability and biological activity through dose adjustments and extended dosing intervals. These interim results have informed plans for a potential Phase 3 study, expected to begin next year. MacroGenics anticipates releasing final safety, efficacy, and durability data, including radiographic progression-free survival details, by the latter half of 2024.

Johann DeBono of The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust confirmed the promising interim safety and antitumor activity in the TAMARACK study. Considering the limited options available to mCRPC patients, this novel ADC molecule could become a significant therapy targeting B7-H3 in prostate cancer.

Vobra duo is an antibody-drug conjugate (ADC) targeting B7-H3, which is widely expressed across multiple solid tumors. The TAMARACK Phase 2 study, which completed enrollment in November 2023, involved two dosing groups (2.0 mg/kg and 2.7 mg/kg every four weeks). Updated interim data as of April 12, 2024, revealed various patient responses and safety profiles. Notably, approximately 50% of patients in both dosing cohorts experienced a PSA reduction of 50% or more. Disease control rates were over 85% in both groups, with confirmed overall response rates varying between 17.8% to 25%.

Regarding safety, almost all participants experienced treatment-emergent adverse events. However, severe adverse events (Grade ≥3) were observed in over half of the participants, with some leading to drug discontinuations or dose modifications. Common side effects included asthenia, nausea, peripheral edema, and decreased appetite. There were five fatal events reported, with ongoing investigations.

MacroGenics also plans to expand TAMARACK to other cancer types such as non-small cell lung cancer, small cell lung cancer, melanoma, squamous cell carcinoma of the head and neck, and anal cancer by mid-2024. Additionally, a Phase 1/2 dose escalation study of vobra duo combined with lorigerlimab in advanced solid tumors is ongoing, with dose expansion anticipated in 2024.

MGC026, another B7-H3-targeting ADC conjugated with exatecan, is in Phase 1 dose escalation for advanced solid tumors, showing greater potency than similar ADCs in preclinical studies. Enoblituzumab, an Fc-optimized monoclonal antibody targeting B7-H3, is under evaluation in the HEAT study for high-risk localized prostate cancer.

Lorigerlimab, a bispecific PD-1 × CTLA-4 DART® molecule, is undergoing a randomized Phase 2 study (LORIKEET) in combination with docetaxel for second-line mCRPC patients. This trial aims to complete enrollment by 2024 with initial updates in 2025.

MacroGenics’ emerging ADC pipeline includes MGC028, targeting ADAM9, anticipated to enter clinical trials by the end of 2024. Preclinical findings reveal specific antitumor activity and tolerable safety profiles, suggesting potential for treating ADAM9-expressing cancers.

Financially, MacroGenics reported a cash position of $184.2 million as of March 31, 2024, with total quarterly revenue at $9.1 million. Research and development expenses were about $46 million, slightly up from the previous year. With a net loss of $52.2 million, the company projects its cash reserves, alongside anticipated future payments and product revenues, to sustain operations into 2026.