STIFEL 2026 HEALTHCARE CONFERENCE - MACROGENICS INC

Financial Performance:

• Secured approximately $290 million in non-dilutive capital over the last 12 months through corporate development and partnerships, strengthening the balance sheet.
• As of Q2, pro forma cash balance is $327 million (including recent milestone payments and asset divestiture proceeds), with actual cash on hand at $173 million.
• Legacy partnerships retain significant latent value: Gilead partnership holds $1.6 billion in milestone potential; Insight partnership includes over $500 million in milestones and royalties (royalty reverts to Macrogenics upon cap realization).
• Divested an embedded CDMO operation earlier in the year to refocus resources.

Guidance and Future Outlook:

• Targeting 2027 as a key inflection point for multiple pipeline updates and program advancements.
• MGC-026 (Head and Neck) dose expansion enrollment of 40 patients expected to conclude by year-end, with data updates anticipated mid-2027.
• Third undisclosed ADC candidate achieved IND submission and clearance in Q2, with first patient dosed; focusing on GI and bladder cancers.
• Next-generation T-cell engager and dual payload ADC strategies are in active preclinical/IND-enabling phases, aiming for new program milestones in 2027.

Business Segments and Product Lines:

• ADC Portfolio (Three Clinical Assets):
  • MGC-026 (B7H3): Presented ESMO data showing 29% response rate in heavily pre-treated populations (86% in 4th line+); focused on Head and Neck, Melanoma, Sarcoma, and Endometrial cancers; evaluating combination with Pembro (pembrolizumab) for frontline settings.
  • MGC-028 (ADAM9): Phase I ongoing with clinical update expected later this year; utilizes Synifex linker/payload platform to avoid ocular toxicity seen in previous ADAM8 iterations; addresses limited competitive landscape.
  • Novel Target ADC: Undisclosed first-in-class target in Phase I dose escalation; indications include Pancreatic, Colorectal, Esophageal, and Bladder cancers.
• T-Cell Engagers:
  • Partnership with Gilead includes three assets: one with a Phase I option decision pending, two fully owned development candidates in IND-enabling work.
  • Lorigerlimab (wholly owned): Migrated from 6mg to 3mg dose to improve safety/tolerability while maintaining activity; 20-patient Clear Cell cohort data expected later this year.

Market and Competitive Landscape:

• Strategically avoiding highly competitive late-stage markets (e.g., SCLC, Prostate) to focus on "white space" and differentiated signals (Head and Neck, Sarcoma).
• B7H3 target validated across 12+ tumor types; differentiating from competitors via TOPA1 payload (vs. statin-based) offering improved safety profile (no treatment-related ILD, lower discontinuation rates).
• ADAM9 field is less crowded compared to B7H3, with Macrogenics leading the race against few competitors (e.g., Duality Bio, B1).
• Competitive landscape in Frontline Head and Neck is intensifying; monitoring data from PDO (GEMDA) regarding EGFR bispecifics.

Risks and Challenges:

• Rising competition in the ADC space, particularly with TOPA1-based mechanisms, necessitates exploration of dual payloads and non-TOPA1 killing mechanisms to mitigate resistance.
• Clinical execution risks in highly pre-treated populations where response rates and tolerability are critical for differentiation.
• Dependency on future partnership options (e.g., Gilead decision based on Phase I data) and the ability to secure additional non-dilutive capital.

Management Commentary and Tone:

• CEO Eric Grisser expressed high confidence and urgency, characterizing the past year as "transformative" with a refocused enterprise.
• Tone is strategic and cautious yet optimistic; management emphasized "judicious" capital allocation to avoid direct head-to-head competition in mature indications.
• Highlighted successful history of deal-making and partnership execution to fund development without dilution.

Analyst Questions and Answers:

• Question on Tumor Type Selection: Confirmed selection based on competitive landscape analysis (avoiding crowded SCLC/Prostate) and early biological signals (29% response across 5 tumor types).
• Question on Prostate Abandonment: Explained that Phase III programs in Prostate are dominated by well-funded competitors (Daiichi Sankyo, Duality Bio), making it an inefficient use of capital for Macrogenics.
• Question on ADAM9 Shedding: Clarified that soluble shed ADAM9 levels are negligible (<10 ng/mL), ruling out antigen sink issues that plagued other targets like Mesothelin.
• Question on Lorigerlimab Dose: Disclosed migration to 3mg dose based on safety data showing 6mg led to higher discontinuation rates; early efficacy maintained at lower dose.
• Question on Partnering Strategy: Stated intent to seek partners for participation rights and long-term upside, not just upfront capital, leveraging the $290M raised and legacy deal structures.

Other Key Points:

• All three clinical ADCs utilize the same Synifex linker/payload technology, which was clinically validated by InnoVent's 18.2 data at ESMO.
• Macrogenics is actively exploring dual payloads and next-gen T-cell engagers (beyond conventional CD3) to address resistance and expand the therapeutic index.
• Zyns (Insight partner) is approved for first-line anal cancer with a global commercialization strategy (US, Europe, Asia) and strong uptake.