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Corporate Presentation August 13, 2025
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Legal Disclaimer 2 This presentation contains âforward-lookingâ statements and information within the meaning of the Private Securities Litigation Reform Act of 1995. These statements may be identified by words such as âaims,â âanticipates,â âbelieves,â âcould,â âestimates,â âexpects,â âforecasts,â âgoal,â âintends,â âmay,â âplans,â âpossible,â âpotential,â âseeks,â âwillâ and variations of these words or similar expressions, although not all forward-looking statements contain these words. Forward-looking statements in this presentation include, but are not limited to, statements regarding Mersana Therapeutics, Inc.âs (âMersanaâ) business strategy, mission and vision; the development and potential of Mersanaâs product candidates, platforms and technology; the potential clinical benefits of Emi-Le (XMT-1660); the design, progression and timing of Mersanaâs clinical trials, including its clinical trials of Emi-Le and XMT-2056; Mersanaâs planned data presentations from these trials; and Mersana's ability to realize the benefits of existing collaborations and enter into new collaborations. Mersana may not actually achieve the plans, intentions or expectations disclosed in these forward-looking statements, and you should not place undue reliance on these forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in these forward-looking statements as a result of various factors, including, among other things, uncertainties inherent in research and development, in the advancement, progression and completion of clinical trials and in the clinical development of Mersana's product candidates, including Emi-Le and XMT-2056; the risk that Mersana may not realize the intended benefits of its platforms, technology and collaborations; the risk that outcomes of preclinical studies may not be predictive of clinical trial results; the risk that initial or interim results from a clinical trial may not be predictive of the final results of the trial or the results of future trials; the risk that clinical trial data may not support regulatory applications or approvals; the risk that Mersana may not realize the intended benefits of its platforms, technology and collaborations; the risk that Mersana's projections regarding its expected cash runway are inaccurate or that the conduct of its business requires more cash than anticipated; and other important factors, any of which could cause Mersana's actual results to differ from those contained in the forward-looking statements, that are described in greater detail in the section entitled âRisk Factorsâ in Mersanaâs Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (âSECâ) on August 13, 2025, as well as in other filings Mersana may make with the SEC in the future. New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties. Any forward-looking statements contained in this presentation speak only as of the date of this presentation, and Mersana expressly disclaims any obligation to update any forward-looking statements contained herein, whether because of any new information, future events, changed circumstances or otherwise, except as otherwise required by law. Mersana owns various trademark registrations and applications, and unregistered trademarks, including Mersanaâs name and its corporate logo. All other trade names, trademarks and service marks of other companies appearing in this presentation are the property of their respective holders. Solely for convenience, the trademarks and trade names in this presentation may be referred to without the ÂŽ, or Š symbols, but such references should not be construed as any indicator that their respective owners will not assert, to the fullest extent under applicable law, their rights thereto. Mersana does not intend to use or display other companies' trademarks and trade names to imply a relationship with, or endorsement or sponsorship of Mersana by, any other companies.
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⢠Encouraging and unique clinical activity observed in post-topo-1 TNBC, an indication with high unmet need, with differentiated safety and tolerability ⢠>40 patients enrolled in expansion in post-topo-1 TNBC at two doses; plan to present initial expansion data in 2H 2025 ⢠Confirmed objective responses observed across all other enrolled tumor types: HR+BC, endometrial cancer, ovarian cancer and ACC-1 ⢠Phase 1 dose escalation ongoing with XMT-2056 ⢠Plan to present initial clinical pharmacodynamic STING activation data in 2025 ⢠Global license option agreement with GSK plc Corporate Overview XMT-2056, an Immunosynthen STING- Agonist HER2 ADC, in Dose Escalation Advancing Emi-Le to Address High Unmet Need in Post-Topo-1 TNBC ACC-1, adenoid cystic carcinoma type 1; ADC, antibody-drug conjugate; HR+BC, hormone-receptor-positive breast cancer; HER2, human epidermal growth factor receptor 2; STING, STimulator of INterferon Genes; TNBC, triple-negative breast cancer; topo-1, topoisomerase-1 inhibitor 3 ⢠Dolasynthen research collaboration with Johnson & Johnson ⢠Immunosynthen research collaboration with Merck KGaA, Darmstadt, Germany ⢠Multiple Dolasynthen and Immunosynthen preclinical ADC candidates available for partnering Discovery Pipeline Leveraging Mersanaâs Proprietary ADC Platforms
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Lack of Platform and Payload Innovation Cytotoxic ADCs remain predominant with few novel mechanisms Focused on Overcoming Today's ADC Limitations 4ADC, antibody-drug conjugate; ILD, interstitial lung disease; IO, immuno-oncology; STING, STimulator of INterferon Genes; topo-1, topoisomerase-1 inhibitor ADCs TODAY First-Generation ADCs Limited by Safety First wave of anti-tubulins dose limited by platform toxicities (neuropathy, neutropenia, ocular toxicity, etc.) Establish the Best-In-Class Anti-Tubulin Platform Dolasynthen designed to overcome dose-limiting ADC platform toxicities to drive greater efficacy and enable combinations with standards of care THE MERSANA OPPORTUNITY Newer Topo-1 ADC Barriers Emerging Hematologic toxicities, ILD and topo-after- topo resistance are limiting this class Provide Effective Alternatives to Topo-1 ADCs Allow for ADCs that avoid resistance mechanisms, severe hematologic toxicities and ILD Establish a New Class of IO ADCs Advance ADCs beyond cytotoxics using STING-agonism to achieve tumor-specific activation of the innate immune system
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Mersanaâs ADC Pipeline 5 * XMT-2056 is wholly owned by Mersana. GSK has an exclusive global license option to co -develop and commercialize the candidate Platform ADC Program Target Indication(s) Preclinical P1 Dose Escalation P1 Dose Expansion Dolasynthen Emi-Le (XMT-1660) B7-H4 Multiple Solid Tumors Immunosynthen XMT-2056 Novel HER2 Epitope Multiple Solid Tumors Dolasynthen Undisclosed Undisclosed Immunosynthen Undisclosed Undisclosed Collaborators * ADC, antibody-drug conjugate; HER2, human epidermal growth factor receptor 2
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Two distinct and proprietary ADC product engines Mersanaâs Next-Generation ADC Platforms 6 Ddidates: ⢠Emi-Le (XMT-1660) ⢠Platform collaboration with Johnson & Johnson ⢠Preclinical development candidates available for partnering ADC, antibody-drug conjugate; DAR, drug-to-antibody ratio; Emi-Le, emiltatug ledadotin; PK, pharmacokinetics; STING, STimulator of INterferon Genes Dolasynthen ⢠Next-generation cytotoxic platform with customizable DAR designed for enhanced PK and tumor delivery ⢠Equipped with a proprietary anti-tubulin payload with controlled bystander effect ⢠Designed to reduce dose-limiting platform toxicities (e.g., severe neuropathy, neutropenia, ocular toxicity, thrombocytopenia, etc.) ⢠Potential to develop product candidates for monotherapy and combination use IProduct Candidates: ⢠XMT-2056 (GSK option) ⢠Platform collaboration with Merck KGaA ⢠Preclinical development candidates available for partnering Immunosynthen ⢠Observed to be a potent stimulator of the innate immune system in the clinic ⢠Equipped with a proprietary payload intended to activate STING in tumor-resident immune cells and antigen-expressing tumor cells (âone-two punchâ) ⢠Potential to develop product candidates for monotherapy and combination use
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Dolasynthen Mersanaâs Next-Generation Cytotoxic ADC Platform ADC, antibody-drug conjugate
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Dolasynthen: A Differentiated Cytotoxic ADC Platform Designed by Leveraging Clinical Learnings 8 Site-specific bioconjugation creates fully homogeneous ADCs using a variety of approaches DAR multiplier matches the optimal DAR to target Hydrophilicity enhancer and charge balance allows for antibody-like PK independent of DAR Differentiated cleavable linker not subject to proteases âControlled bystanderâ payload causes immunogenic cell death and retains activity in topo-1 resistant tumors preclinically. Avoids dose- limiting neutropenia, neuropathy and ocular toxicity in the clinic Very Low Cell Permeability Blocks Bystander Killing; Not a PgP Substrate Cell-Permeable Bystander Killing Metabolic Conversion in Tumor Cell Auristatin F-HPA (AF-HPA) Auristatin F (AF) h Controlled Bystander MOA ADC, antibody-drug conjugate; DAR, drug-to-antibody ratio; HPA, hydroxypropylamide; PgP, P-glycoprotein; PK, pharmacokinetics; topo-1, topoisomerase-1 inhibitor
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DAR, drug-to-antibody ratio; TNBC, triple-negative breast cancer; topo-1, topoisomerase-1 inhibitor Emiltatug Ledadotin (Emi-Le; XMT-1660) Platform: Dolasynthen Target: B7-H4 DAR: 6 Status: Phase 1 dose expansion ongoing in patients with TNBC who have received 1-4 prior lines of therapy, including at least 1 prior topo-1 ADC
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Background on B7-H4 and Emi-Le B7-H4 ⢠Clinically validated target highly expressed in TNBC, HR+BC, endometrial cancer, ovarian cancer, ACC-1; limited healthy tissue expression ⢠Negative prognostic factor for various tumors ⢠Novel ADC design: Homogeneous DAR 6 Dolasynthen ADC ⢠Two FDA Fast Track designations granted for the treatment of: â TNBC (including patients who have received a prior topo-1 ADC) â Certain HR+ breast cancer patients 10 Emi-Le 1. Wang et al., Cancer Cell Int., 2018 ACC-1, adenoid cystic carcinoma type 1; ADC, antibody-drug conjugate; DAR, drug-to-antibody ratio; FDA, U.S. Food and Drug Administration; HR+BC, hormone-receptor positive breast cancer; TNBC, triple-negative breast cancer; topo-1, topoisomerase-1 inhibitor; TNBC Overall Survival by B7-H4 Expression1
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Global relapsed/refractory TNBC market projected to exceed $1 billion annually starting in 20251 Recent positive Phase 3 results2 for topo-1 ADCs in front-line setting may substantially expand post-topo-1 TNBC patient population ORR of 5%, PFS of 1.7 months, OS of 6.7 months for standard of care single-agent chemo in relapsed/ refractory TNBC3 Significant and Growing Unmet Need in Relapsed/Refractory TNBC 11 1. Includes TD Cowen analyst estimate in August 2025 report for global sales of an approved therapeutic for treatment of relapse d/refractory TNBC 2. Includes ASCENT-03 and ASCENT-04 clinical trials of sacituzumab govitecan; Tolaney et al., ASCO 2025; Gilead Sciences press release, May 23, 2025 3. ASCENT Phase 3 clinical trial of sacituzumab govitecan; Bardia et al., NEJM 2021 ADC, antibody-drug conjugate; ORR, objective response rate per RECIST version 1.1; OS, overall survival; PFS, progression-free survival; TNBC, triple-negative breast cancer; topo-1, topoisomerase-1 inhibitor
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Increasing Real-World Data Suggest Topo-1 Payload Resistance Greatly Reduces Clinical Benefit 12 1. Tarantino et al. ASCO 2024. 2. Huppert et al., NPJ Breast Cancer. 2025 ADC, antibody-drug conjugate; ASCO, American Society of Clinical Oncology; CI, confidence interval; HER2, human epidermal growth factor receptor 2; HR+, hormone-receptor-positive; IntTx, intervening chemotherapy; OS, overall survival; rwPFS, real-world progression-free survival; SG, sacituzumab govitecan (TRODELVYÂŽ); T-DXd, trastuzumab deruxtecan (ENHERTUÂŽ); TNBC, triple-negative breast cancer; topo-1, topoisomerase-1 inhibitor Outcomes Data for Trastuzumab Deruxtecan Patients With / Without Prior Sacituzumab Govitecan (TNBC)1 PFS Data for Patients Receiving Two Topo-1 ADC Treatment Lines (HR+/HER2-Low)2
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Emi-Le: Well Positioned in the B7-H4 Landscape Asset Company Linker Payload Conjugation Drug-to- Antibody Ratio First Patient Dosed in Phase 1 emiltatug ledadotin (Emi-Le; XMT-1660) Mersana Cleavable (esterase) Anti-Tubulin (AF-HPA) Site Specific DAR 6 Q3 2022 puxitatug samrotecan (AZD8205) AstraZeneca Cleavable (protease) Topo-1 Inhibitor Fully Reduced Cysteine DAR 8 Q1 2022 GSK5733584 (HS-20089) GSK (licensed from Hansoh Pharma) Cleavable (protease) Topo-1 Inhibitor Undisclosed DAR 6 Q1 2022 BG-C9074 BeiGene (licensed from Duality Biologics) Undisclosed Topo-1 Inhibitor Undisclosed DAR 6 Q2 2024 LNCB74 NextCure (partnered with LigaChem) Cleavable (glucuronidase) Anti-Tubulin (MMAE) Site Specific DAR 4 Q1 2025 13 ADC, antibody-drug conjugate; AF-HPA, auristatin F-hydroxypropylamide; DAR, drug-to-antibody ratio; MMAE, monomethyl auristatin E; topo-1, topoisomerase-1 inhibitor Clinical-Stage B7-H4 ADC Candidates Potentially subject to topo-1 ADC resistance Post-topo-1 ADC activity unknown Active post- topo-1 ADCs
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Emi-Le Clinical Data from Phase 1 Dose Escalation and Backfill Cohorts
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Emi-Le Phase 1 Dose Escalation and Expansion 15 * Includes a range of doses and schedules. All patients enrolled in the U.S. ACC-1, adenoid cystic carcinoma â type 1; ADA, anti-drug antibody; ADC, antibody-drug conjugate; D1/D8, administered on days 1 and 8 of the cycle; DCR, disease control rate; DES, dose escalation; DOR, duration of response; EC, endometrial cancer; ECOG PS, Eastern Cooperative Oncology Group performance status; HR+/HER2- BC, hormone-receptor-positive, human epidermal growth factor receptor 2 negative breast cancer; mg/m2, milligrams per meter squared; MTD, maximum tolerated dose; OC, ovarian cancer; ORR, overall response rate; PK, pharmacokinetics; Q4W, dosing every four weeks; RP2D, recommended phase 2 dose; TNBC, triple-negative breast cancer; topo-1, topoisomerase-1 inhibitor Key Enrollment Criteria: ⢠atients âĽ18 years old ⢠ECOG PS 0-1 ⢠Advanced/metastatic TNBC, HR+/HER2- BC, EC, OC, ACC-I ⢠Progressed after available standard of care therapy 7.2 â 28.7 mg/m2 38.1 â 67.4 mg/m2 76.2 â 115.0 mg/m2 Subtherapeutic Dose Range* (n=16) Intermediate Dose Range* (n=83) High Dose Range* (n=42) Key Enrollment Criteria: ⢠Advanced or metastatic TNBC ⢠1-4 prior lines of treatment in locally advanced or metastatic setting, including at least one prior topo-1 ADC Dose Escalation and Backfill Cohorts Ongoing Dose Expansion in TNBC Primary Endpoints: MTD, safety and tolerability Secondary Endpoints: ORR, DOR, DCR, PK, ADA Primary Endpoints: Safety, tolerability and preliminary antitumor activity Secondary Endpoints: PK and ADA Dose A: 67.4 mg/m2 Q4W Dose B: 80 mg/m2 Q4W with a loading dose of 44.5 mg/m2 on D1/8 of 1st 4-week cycle ⢠B7-H4 expression assessed retrospectively based on fresh or archived tissue ⢠In parallel with DES, backfill cohorts enrolling additional participants at multiple dose levels ⢠Data from both DES and backfill cohorts will be utilized to determine the RP2D Patients stratified by B7-H4 expression March 8,2025 data cut-off
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Most patients had breast cancer and received at least one prior topo-1 ADC Dose Escalation and Backfill Demographics 16 1. Archival or fresh tissue evaluated retrospectively by IHC for B7 -H4 expression with a preliminary high cut off set at Tumor Prop ortion Score (T S)âĽ70 ACC-1, adenoid cystic carcinoma â type 1; ADC, antibody-drug conjugate; ECOG PS; ECOG performance status; HR+/HER2- MBC, hormone-receptor-positive, human epidermal growth factor receptor 2 negative metastatic breast cancer; TNBC, triple-negative breast cancer; topo-1, topoisomerase-1 inhibitor; TPS, tumor proportion score Replace chart TNBC (N=63) HR+/HER2- MBC (N=37) Ovarian (N=14) Endometrial (N=14) ACC-I (N=13) Total (N=141) Median age 48 62 61 65.5 52 55 Median prior lines of therapy (range) 5 (2-9) 7 (2-15) 5 (2-11) 3 (1-4) 1 (0-3) 4 (0-15) Prior Topo-1 ADCs received, n (%) Prior trastuzumab deruxtecan 21 (33.3%) 15 (40.5%) 0 0 0 36 (25.5%) Prior sacituzumab govitecan 54 (85.7%) 15 (40.5%) 0 0 1 (7.7%) 70 (49.6%) Prior both 17 (27.0%) 10 (27.0%) 0 0 0 27 (19.1%) Prior either 58 (92.1%) 20 (54.1%) 0 0 1 (7.7%) 79 (56.0%) B7-H4 Expression1, n (%) TPS Known 53 (84.1%) 31 (83.8%) 13 (92.9%) 14 (100%) 5 (38.5%) 116 (82.3%) High (TPS âĽ70) 24 (45.3%) 8 (25.8%) 7 (53.8%) 5 (35.7%) 4 (80.0%) 48 (41.4%) Low (TPS <70) 29 (54.8%) 23 (74.2%) 6 (46.2%) 9 (64.3%) 1 (20.0%) 68 (58.6%) TPS Unknown 10 (15.9%) 6 (16.2%) 1 (7.1%) 0 8 (61.5%) 25 (17.7%) March 8,2025 data cut-off
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Safety Summary: Emi-Le Observed to be Generally Well Tolerated 17 Total (N=141) Any treatment related adverse event (TRAE) 117 (83.0%) Grade 3 TRAE 52 (36.9%) Treatment-related serious adverse event (SAE) 8 (5.7%) TRAE leading to treatment discontinuation 5 (3.5%) TRAE leading to dose reduction 23 (16.3%) TRAE leading to dose delay 33 (23.4%) TRAE leading to death 0 ⢠Most common TRAEs were transient AST increase, generally asymptomatic and reversible proteinuria, generally low-grade fatigue and nausea ⢠Reasons for discontinuation: proteinuria (G3), infusion related reaction (G3), nephrotic syndrome in the presence of gout flare (G3), cystitis hemorrhagic (G2), pain in extremity (G2) ⢠No dose-limiting treatment-related neuropathy, neutropenia, ocular toxicity, ILD, or thrombocytopenia observed in this data set TRAEs Observed in âĽ10% of patients (N=141) All Doses 44 40 33 31 18 17 13 12 11 11 0 10 20 30 40 50 60 70 80 90 100 Percentage (%) of Patients 17 14 1 6 1 1 1 G3 G1-2 Pyrexia Platelet count decreased ALP increased ALT increased Anaemia Decreased appetite Nausea Fatigue Proteinuria AST increased ALP, alkaline phosphatase; ALT, alanine transaminase; AST, aspartate aminotransferase; G, grade; ILD, interstitial lung disea se; SAE, serious adverse event; TNBC, triple-negative breast cancer; TRAE, treatment-related adverse event Note: AST increases were transient, increasing by Day 8 and returning to baseline or G1 by subsequent dose. March 8,2025 data cut-off
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Evaluable population (N=114) consists of patients with measurable disease at baseline and at least one post -baseline scan. Of the 141 patients in the safety population, 11 did not have measurable disease at baseline or were ongoing without a post-baseline scan, and 16 discontinued prior to first scan (including 1 B7 -H4 high ovarian cancer patient in the Intermediate Dose Range and 1 B7 -H4 high TNBC patient in the High Dose Range). Missing from waterfall but included in the evaluable population (N=114) are 5 patients with progressive disease as best respo nse who had a post-treatment scan but not post -baseline measurement of their target lesion. mg/m2, milligrams per meter squared; TNBC, triple -negative breast cancer Clinical Activity in Evaluable Patients Correlated With Both Dose and B7-H4 Expression 18 c c c c u c c c c u c c c c -100 -80 -60 -40 -20 0 20 40 60 80 100 120 Best Change in Target Lesion Size from Baseline (%) B7-H4 Not Yet Available (N=17)B7-H4 High (N=42)B7-H4 Low (N=55) 38.1 mg/m2 38.1 - 67.4 mg/m2 76.2 mg/m2 (N=14) (N=67) (N=33) âĽ< Subtherapeutic Dose Range Intermediate Dose Range High Dose Range * = Ongoing treatment C = Confirmed responder U = Ongoing unconfirmed responder March 8,2025 data cut-off
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Intermediate Dose Range: Encouraging Clinical Activity in Evaluable Patients With B7-H4 High Tumors 19 Evaluable population (N=26) defined as patients with measurable disease at baseline and at least one post -baseline scan. Missing from waterfall, but included in response rate denominator, is one TNBC patient with 8 prior lines and progressive disease as best response who had a post -treatment scan but not post -baseline measurement of their target lesion ACC-1, adenoid cystic carcinoma â type 1; Endo, endometrial cancer; HR+BC , hormone-receptor-positive, human epidermal growth factor receptor 2 negative metastatic breast cancer; ORR, objective response rate per RECIST version 1.1; PR, confirmed partial response; TNBC, triple-negative breast cancer ⢠31% (8/26) ORR ⢠TNBC: ORR 23% (3/13) ⢠Endometrial: ORR 50% (2/4) ⢠44% (7/16) ORR in evaluable patients with ⤠prior lines of therapy ⢠TNBC: ORR 29% (2/7) * = treatment ongoing March 8,2025 data cut-off
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Key Benchmarks in Late-Stage TNBC 20 ASCENT Phase 3 PFS3 Single-agent chemo was the physicianâs choice (eribulin, vinorelbine, capecitabine, or gemcitabine) 1. Patients without brain metastases 2. Bardia et al. NEJM 2021 April 22; 384(16): 1529-1541 (including supplementary material) 3. https://www.ema.europa.eu/en/documents/assessment-report/trodelvy-epar-public-assessment-report_en.pdf ASCENT Phase 3 OS2 ASCENT Phase 3 ORR2 Population1 Sacituzumab Govitecan Single-Agent Chemo Overall 35% 5% >3 Prior Therapies 23% 6% Overall 5.6 months 1.7 months >3 Prior Therapies 4.2 months 2.2 months Overall 12.1 months 6.7 months >3 Prior Therapies 12.1 months 7.1 months
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Intermediate Dose Range: Clinical Activity in Evaluable Patients With B7-H4 High Post-Topo-1 TNBC T T T T T T T TT TT TT T T 3 5 4 5 4 5 4 4 5 4 5 4 PR PR PR -100 -80 -60 -40 -20 0 20 40 60 80 100 120 Best Change in Target Lesion Size from Baseline (%) Confirmed ORR: 23% (3/13) # of prior lines Prior topo-1 ADC(s) T = Previously treated with one topoisomerase-1 inhibitor ADC TT = Previously treated with more than one topoisomerase-1 inhibitor ADC Evaluable population defined as patients with measurable disease at baseline and at least one post -baseline scan. One patient did not have target lesions identified at baseline and is therefore not included. Missing from waterfall, but included in response rate denominator, is one T NBC patient with 8 prior lines, including topo-1 ADC and progressive disease as best response who had a post -treatment scan but not post-baseline measurement of their target lesion ADC, antibody-drug conjugate; CI, confidence interval; ORR, objective response rate; TNBC, triple -negative breast cancer; topo-1, topoisomerase-1 inhibitor 21 ⢠Heavily pre-treated patient population (median of four prior treatment lines) ⢠All received at least one prior topo-1 ADC ⢠Confirmed ORR was 29% (2/7) in patients with ⤠prior lines in locally advanced/metastatic setting March 8,2025 data cut-off
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Intermediate Dose Range: Preliminary Time-to-Event Data in Evaluable Patients with B7-H4 High TNBC 22Evaluable population defined as patients with measurable disease at baseline and at least one post -baseline scan. NR, not reached; TNBC, triple-negative breast cancer; wks, weeks Preliminary Progression Free Survival (PFS) â¤4 prior lines: B7-H4 High vs B7-H4 Low B7-H4 High: NR B7-H4 Low: 5.7 months Preliminary Overall Survival (OS) â¤4 prior lines: B7-H4 High vs B7-H4 Low B7-H4 High: 16 weeks B7-H4 Low: 6.4 weeks March 8,2025 data cut-off
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High Dose Range: Preliminary Data Suggest Potential for Even Greater Clinical Activity 23CR, complete response; mg/m2; milligrams per meter squared; ORR, objective response rate; PR, partial response; Q4W, dosing e very four weeks ⢠Clinical data suggest a dose-response relationship with Emi-Le ⢠7 of the 11 evaluable patients at doses >67.4 mg/m2 achieved tumor reductions of âĽ30% ⢠Believe the confirmed ORR at doses >67.4 mg/m2 was impacted by proteinuria-related dose delays that had been mandated under original clinical trial protocol ⢠Protocol amended in late January 2025 with the goal of mitigating dose delays ⢠Now actively enrolling patients in expansion at 80 mg/m2 Q4W with a loading dose of 44.5 mg/m2 on Days 1 and 8 of first four-week cycle* = treatment ongoing March 8,2025 data cut-off
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Enrollment Now Underway in Both Expansion Cohorts in Post-Topo-1 TNBC 24 Primary Objectives: Assess safety, tolerability and preliminary antitumor activity Secondary Objectives: Assess PK and ADA ⢠Advanced or metastatic TNBC ⢠1 to 4 prior lines of treatment, including at least one prior topo-1 ADC ⢠ER-, PR-, HER2- based on local testing of their most recent biopsy as defined in ASCO/CAP guidelines o Patients with HR+BC at diagnosis permitted o Patients with HER2 IHC 0, IHC 1, or IHC 2/ISH negative permitted ⢠Patients stratified by B7-H4 expression status Dose A: 67.4 mg/m2 Q4W Dose B: 80 mg/m2 Q4W with a loading dose of 44.5 mg/m2 on D1/8 of 1st 4-week cycle Dose A: 67.4 mg/m2 Q4W Dose B: 80 mg/m2 Q4W with a loading dose of 44.5 mg/m2 on D1/8 of 1st 4-week cycle Stage 1 Stage 2 Select Dose and Biomarker Cutoff for Potential Pivotal Trial ACC-1, adenoid cystic carcinoma â type 1; ADA, anti-drug antibody; ADC, antibody-drug conjugate; ASCO/CAP, American Society of Clinical Oncology and the College of American Pathologists; ER -, estrogen receptor negative; HER2-, human epidermal growth factor receptor 2 negative; HR+/HER2- BC, hormone-receptor-positive, human epidermal growth factor receptor 2 negative breast cancer; IHC, immunohistochemistry; ISH, in situ hybridization; mg/m2, milligrams per meter squared; PK, pharmacokinetics; PR-, progesterone receptor negative; Q4W, dosing every four weeks; TNBC, triple-negative breast cancer; topo-1, topoisomerase-1 inhibitor Enrollment Criteria >45 patients enrolled in Stage 1 of expansion; expect to report initial clinical data from expansion in second half of 2025
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Pursuing a Unique Opportunity in Post-Topo-1 TNBC with Broader Clinical Potential Unique and Encouraging Clinical Activity in Post-Topo-1 TNBC, an Indication With High Unmet Need Differentiated Safety and Tolerability Profile TNBC, triple-negative breast cancer; topo-1, topoisomerase-1 inhibitor 25 Broader Clinical Activity and Potential in Other B7-H4-Expressing Tumors
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Immunosynthen Mersanaâs STING-Agonist ADC Platform ADC, antibody-drug conjugate; STING, STimulator of INterferon Genes
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Immunosynthen: Our Proprietary STING-Agonist ADC Platform 27 Designed to Localize STING Activation to Increase Potency and Decrease Systemic Toxicity ADC, antibody-drug conjugate; FcyR, Fc gamma receptor for immunoglobulin G; IFN, interferon; STING, STimulator of INterferon Genes Immunosynthen ADCFree STING Agonist Gulen et al. Nature Comm. 2017 Wu et al. Immunity 2020 Diffusion Passive, indiscriminate diffusion Less efficient delivery to desired cell types Proapoptotic activation of T cells (Type I IFN independent) No delivery to T cells Fcď§R-mediated, active delivery into tumor- resident myeloid and dendritic cells Active delivery Antigen-dependent, active delivery into tumor cells Duvall et al. Journal of Medicinal Chemistry. 2023
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XMT-2056 Platform: Immunosynthen Target: HER2 (novel epitope) DAR: 8 Initial Cancers of Interest: HER2+ breast, gastric, colorectal and non-small-cell lung cancers DAR, drug-to-antibody ratio; HER2+, human epidermal growth factor receptor 2 positive
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First-in-class STING-agonist ADC targeting a novel HER2 epitope XMT-2056: Our Lead Immunosynthen ADC 29 ⢠Targets a HER2 epitope distinct from pertuzumab and trastuzumab, providing the potential for both monotherapy and combination activity ⢠Evidence of strong preclinical activity in both HER2-high and HER2-low tumor models ⢠Granted Orphan Drug designation from FDA for gastric cancer ⢠Enrollment ongoing in Phase 1 dose escalation (NCT05514717) ADC, antibody-drug conjugate; FDA, U.S. Food and Drug Administration; HER2, human epidermal growth factor receptor 2; STING, STimulator of INterferon Genes
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A Single Dose of XMT-2056 Drives Strong Monotherapy and Combination Activity in Multiple Preclinical Models 30 XMT-2056 Enhances Activity of Trastuzumab Deruxtecan XMT-2056 Enhances Activity of Anti-PD-1 XMT-2056 Strong Activity at 0.1 mg/kg Dose Strong Activity in HER2 High 0 7 14 21 28 35 42 49 56 63 0 200 400 600 Days on Study Mean Tumor Volume ďąSEM (mm3) Note: xenograft model in immunocompromised mice Note: xenograft model in immunocompromised mice 0 7 14 21 28 35 0 500 1000 1500 2000 Days on Study Mean Tumor Volume ďąSEM (mm3) Vehicle XMT-2056 surrogate 0.3 / 0.010 mg/kg ďĄ-PD-1 5 mg/kg XMT-2056 surrogate 0.3 / 0.010 mg/kg + ďĄ-PD-1 5 mg/kg Non-binding control ADC 0.3 / 0.012 mg/kg + ďĄ-PD-1 5 mg/kg Note: syngeneic ratHER2 expressing model in immunocompetent mice 0 7 14 21 28 35 42 49 56 63 0 500 1000 1500 Days on Study Mean Tumor Volume ďąSEM (mm3) Vehicle XMT-2056 1 / 0.043 mg/kg Enhertu 3 / 0.078 mg/kg Enhertu 10 / 0.261 mg/kg XMT-2056 1 / 0.043 mg/kg + Enhertu 3 / 0.078 mg/kg XMT-2056 1 / 0.043 mg/kg + Enhertu 10 / 0.261 mg/kg Note: xenograft model in immunocompromised mice Time of administration(s) ADC, antibody-drug conjugate; HER2, human epidermal growth factor receptor 2; ISAC, immune-stimulating antibody conjugate; mg/kg, milligrams per kilogram; mm, millimeter; PD-1, programmed cell death protein 1; SEM, standard error of mean; TLR, toll-like receptor XMT-2056 0.1 / 0.004 mg/kg qwkx3 0 7 14 21 28 35 42 49 56 63 70 77 0 200 400 600 800 1000 Mean Tumor Volume +/- SEM (mm3)
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XMT-2056 Phase 1 Dose Escalation Design 31 Dose Escalation (DES) Primary Endpoints MTD or RP2D, safety and tolerability Secondary Endpoints ORR, DOR, DCR, PK, ADA Bayesian optimal interval design for dose escalation XMT-2056 via IV q21 days (Q3W) Tumor assessment every other cycle Select Enrichment Cohorts (SECs) Primary Endpoint Safety and tolerability Secondary Endpoints ORR, DOR, DCR, PK, ADA ⢠In parallel with DES, SECs may enroll participants into tumor type-specific cohorts at cleared dose level(s) from DES ⢠SECs will include 2 BC enrichment cohorts: HER2+ BC and HER2-low BC, and may also include other cohorts of HER2+ cancers ⢠Data from both DES and SECs will be utilized to determine the RP2D ADA, anti-drug antibody; BC, breast cancer; CRC, colorectal cancer; DCR, disease control rate; DOR, duration of response; GC, gastric cancer; GEJC, gastroesophageal junction cancer; HER2+, human epidermal growth factor receptor 2 positive; IHC, immunohistochemistry; ISH, in-situ hybridization; IV, intravenous; MTD, maximum tolerated dose; N, number of patients; NSCLC, non-small-cell lung cancer; ORR, objective response rate; PK, pharmacokinetics; q21, every 21; RP2D, recommended Phase 2 dose Indications for DES and Enrichment Cohorts HER2+ BC HER2+ GC/GEJC HER2+ CRC HER2+ NSCLC Other HER2+ Cancers HER2+ defined as IHC 3+ or 2+/ISH+
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ACC-1: An Aggressive Tumor with Poor Prognosis, No Approved Treatments and High B7-H4 Expression 33 Tumor Background Mainly in salivary gland, also in breast, eye, trachea, reproductive tract US Incidence1,2 ~700 patients Median Overall Survival2 ~3 years Treatments ⢠No systemic treatments approved ⢠Surgery + radiation, followed by single-agent chemo (platinum, taxanes, gemcitabine) and/or VEGF TKIs ⢠Typically 1-2 lines of systemic treatment B7-H4 Expression3 80-85% Other Relevant Biology Upregulation of MYC and enrichment of NOTCH1- activating mutations Clinical Precedents Limited success with investigational VEGF TKI and NOTCH inhibitors achieving 5-17% ORR in Ph 2 studies4,5 1. Boyle et al 2020, Journal of Clinical Oncology; 2. Ferrarotto et al 2021, Clin Cancer Research; 3. L. G. Sousa et al. 2023, Clin Cancer Research 2023; 4. Hoff et al 2024, JAMA Otolaryngol Head Neck Surg.; 5. Hoff et al 2025, Cancer Med. Ellington et al 2012, Cancer, SEER database ORR, objective response rate; TKI, tyrosine kinase inhibitor; VEGF, vascular endothelial growth factor Ferrarotto et al.; Clin Cancer Research 2021 L. G. Sousa et al. Clin Cancer Res 2023
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Clinical Activity in Patients with ACC-1, All Doses, Unselected for B7-H4 Expression 34 Tumor Reduction in Evaluable Patients Preliminary PFS in all ACC-1 Patients uPR PR PR PR PR -100 -80 -60 -40 -20 0 20 40 Best Change in Target Lesion Size from Baseline (%) 20% -30% ORR (uPR + PR): 55.6% (5/9)** * = Ongoing treatment uPR = Ongoing unconfirmed responder PR = confirmed responder ** Includes one uPR, which was confirmed after the data cut-off At data cut-off, 4 patients were ongoing in treatment, but did not have their first scan yet. Patients are excluded from waterfa ll and are censored at study day 1 in PFS plot ACC-1, adenoid cystic carcinoma type 1; NR, not reached; ORR, objective response rate; PFS, progression free survival March 8,2025 data cut-off
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Emi-Le ACC-1 Patient Case 35ACC-1, adenoid cystic carcinoma type 1; cm, centimeter; NR, not reached; ORR, overall response rate; PFS, progression free survi val Left posterior lung base pleural nodularity measures: 5.8 x 2.0 cm Baseline Left posterior lung base pleural nodularity measures: 3.9 x 1.7 cm Cycle 2 Day 15 No measurable disease in the chest Post Cycle 5 (post March 8 data cut-off) March 8,2025 data cut-off