MacroGenics Eyes $200M Cash Boost, 2028 Runway Ahead of Cancer Pipeline Updates

Key Points

• MacroGenics expects more than $200 million in near-term cash from a ZYNYZ royalty monetization deal and the pending sale of its manufacturing unit, which should extend its cash runway through the end of 2028.
• The company is preparing a series of pipeline updates, including midyear data on the B7-H3 ADC MGC026, later-year updates on MGC028, and further work on lorigerlimab in clear cell gynecologic cancer.
• MacroGenics says its ZYNYZ royalty stream is benefiting from strong sales growth, while also retaining potential milestone upside and the option to use ZYNYZ in future combination studies.

MacroGenics NASDAQ: MGNX Chief Executive Officer Eric Risser said the biotechnology company has strengthened its balance sheet through two recent transactions while preparing for a series of clinical updates across its oncology pipeline.

Speaking during an informal discussion hosted by Stifel senior biotech analyst Stephen Willey, Risser said MacroGenics has had “a good, strong start to the year” and is focused on sharpening its pipeline strategy, maximizing asset value and extending its financial runway.

Balance Sheet Bolstered by Royalty and Manufacturing Deals

Risser highlighted two transactions announced within a week of each other. The first was a second royalty monetization agreement tied to ZYNYZ with Sagard Health, which could bring in between $60 million and $80 million. He said $60 million has already been received, while an additional $20 million depends on 2026 sales-based performance.

The second transaction is the pending sale of MacroGenics’ manufacturing operation to Bora Pharmaceuticals, a Taiwan-based global contract development and manufacturing organization. Risser said the Bora deal would provide $122.5 million upon closing, which the company is targeting no later than the third quarter of this year.

Together, the transactions could generate more than $200 million in near-term cash, according to Risser. He said MacroGenics now expects its cash runway to extend through the end of 2028. On a pro forma basis, he said the company would have more than $330 million in cash, including $154 million reported at the end of March and potential proceeds from the Bora and Sagard transactions.

Risser also said the amended Sagard agreement reflects improved economics compared with the original structure. The original capped royalty structure provided Sagard a 2.0x return, while the new agreement includes a 1.7x multiple that could also apply to the earlier tranche of capital depending on the sales ramp.

ZYNYZ Royalties and Potential Combinations

Risser said ZYNYZ has seen a strong commercial ramp, with Incyte reporting about $40 million in first-quarter sales, a roughly tenfold increase from a year earlier. He noted that frontline anal cancer has been approved in the U.S., Europe and Japan.

MacroGenics has disclosed royalties on ZYNYZ of 15% to 24%, and Risser said the company has about $540 million in aggregate milestone potential remaining. If royalty caps are reached, he said the royalty would fully revert to MacroGenics. Incyte is leading global commercialization, and Risser deferred to Incyte for further regulatory updates.

Risser said MacroGenics retains the ability to access ZYNYZ for combination studies with its wholly owned pipeline, describing that as an opportunity as oncology development increasingly moves toward combination therapy.

Lorigerlimab Focuses on Clear Cell Gynecologic Cancer

Willey asked about the Phase 2 LYNET trial evaluating single-agent lorigerlimab in gynecologic malignancies, including clear cell and platinum-resistant ovarian cancer. Risser said the company previously studied doses ranging from 1 mg/kg to 10 mg/kg and selected 6 mg/kg for earlier expansion cohorts and the LYNET study.

Risser said newer pharmacokinetic and pharmacodynamic modeling suggests complete PD-1 receptor occupancy can occur at lower doses, including 1 mg/kg, with evidence of T-cell activation and CTLA-4 blockade markers at 1 mg/kg and 3 mg/kg. MacroGenics is now exploring whether a lower 3 mg/kg dose can improve safety and tolerability.

He said the company has not seen some hallmark toxicities typically associated with ipilimumab, such as frequent serious colitis. However, Risser said hematologic toxicities have been observed, including thrombocytopenia and neutropenia. He said a prior clinical hold was based on four Grade 4 events, one of which later became fatal.

MacroGenics discontinued its platinum-resistant ovarian cancer effort after it did not meet a prespecified efficacy threshold. Risser said later-line clear cell gynecologic cancer is generally refractory to chemotherapy, with single-digit response rates and short progression-free survival, but may be more responsive to immunotherapy. He said 20 additional patients at 3 mg/kg should help clarify the therapeutic window and dosing for lorigerlimab.

ADC Updates Expected for MGC026 and MGC028

Risser also discussed MGC026, a B7-H3-targeting topoisomerase 1 inhibitor antibody-drug conjugate. He said the molecule uses Synaffix’s GlycoConnect technology, enabling site-specific conjugation, and an exatecan-based cytotoxin. He contrasted the construct with other B7-H3 ADC programs that use more random cysteine-based conjugation approaches.

MacroGenics completed dose escalation for MGC026 late last year and has started multiple tumor-specific expansion cohorts at a selected dose level. Risser said the company expects to provide a midyear clinical update, including more detail on lead indications and future development strategy. He also said no interstitial lung disease has been observed in studies of MGC026 or MGC028.

Risser said MacroGenics does not intend to prioritize small cell lung cancer for MGC026 because other B7-H3 ADCs are already advancing into late-stage and frontline development. He said resistance to repeat use of topoisomerase 1-based ADCs is a real consideration in selecting indications.

MGC028, an ADAM9-targeting ADC using the same linker-payload platform as MGC026, remains in dose escalation. Risser described it as a first-in-class program and said MacroGenics expects a clinical update later this year. Potential tumor types include gastric, colorectal, pancreatic and lung cancers.

Gilead Collaboration and Earlier Research

Risser said MacroGenics’ collaboration with Gilead includes three active programs, led by a CD123 x CD3 bispecific targeting AML, MDS and other CD123-positive hematologic malignancies. One program is in the clinic and two are preclinical. He said the original agreement included about $1.7 billion in potential milestone payments, with approximately $100 million already collected across the three molecules.

Looking ahead, Risser said MacroGenics’ research team continues to generate about one investigational new drug application per year, with an increasing focus on first-in-class approaches. He said MGC030, another topoisomerase 1-based program, is expected to move into the clinic later this year, while additional product candidates are being developed in next-generation T-cell engagers and future ADC approaches.

About MacroGenics NASDAQ: MGNX

MacroGenics, Inc is a clinical-stage biopharmaceutical company focused on the discovery and development of monoclonal antibody–based therapeutics for the treatment of cancer and autoimmune diseases. The company leverages proprietary Fc engineering technologies to enhance immune engagement and extend the activity of its antibodies. Since its founding in 2000, MacroGenics has advanced several product candidates through clinical trials, most notably margetuximab, a HER2-targeted antibody designed to improve outcomes in patients with HER2-positive breast cancer.

Central to MacroGenics' research platform are its ADAPTIR and Trident bispecific antibody technologies.

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