Mersana Therapeutics : Initial Phase 1 Dose Escalation Data for Emi Le (emiltatug ledadotin; XMT 1660) Clinical Data Presentation

Published: 2025-01-10 09:22:30 ET MRSN

Initial Phase 1 Dose Escalation Data for Emi-Le (emiltatug ledadotin; XMT-1660)

January 10, 2025

While today's ADCs provide

Mersana is focused on

developing novel platforms

substantial benefits to some

and payloads that enable

patients, significant platform

ADCs with meaningfully

and payload limitations remain.

improved safety and efficacy.

ADCs, antibody-drug conjugates

Innovating to Overcome Today's ADC Limitations

Focus for Today

ADCs TODAY

First-Generation ADCs Limited by Safety

First wave of anti-tubulins dose limited by platform toxicities (neuropathy, neutropenia, ocular toxicity, etc.)

Newer Topo ADC Barriers Emerging

Hematologic toxicities, ILD and topo-after-

topo resistance are limiting this class

THE MERSANA OPPORTUNITY

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

Provide Effective Alternatives to Topo-1 ADCs

Allow for ADCs that avoid resistance mechanisms, severe

hematologic toxicities and ILD

Lack of Platform and Payload Innovation

Establish a New Class of IO ADCs

Cytotoxic ADCs remain predominant

Advance ADCs beyond cytotoxics using STING-agonism

with few novel mechanisms

to achieve tumor-specific activation of the innate immune system

ADC, antibody-drug conjugate; ILD, interstitial lung disease; IO, immuno-oncology; STING, STimulator of INterferon Genes; topo-1, topoisomerase-1 inhibitor

Background on B7-H4 and Emi-Le

B7-H4Target: Clinically validated and highly expressed in a range of solid tumors with limited healthy tissue expression

Emi-Le

$1 billion annually starting in 20254

4. Based on TD Cowen analyst estimate in November 2024 report for global sales of approved therapeutic for treatment of relapsed/refractory TNBC

ADC, antibody-drug conjugate; DAR, drug-to-antibody ratio; FDA, U.S. Food and Drug Administration; HNSCC, head and neck squamous cell carcinoma; HER-2, human epidermal growth factor receptor 2; HR+, hormone-receptor positive; IHC,

immunohistochemistry; ORR, objective response rate per RECIST version 1.1; TNBC, triple-negative breast cancer; PFS, progression-free survival; sqNSCLC, squamous non-small-cell lung cancer

Emi-Le: A Potential Best-in-Class B7-H4 ADC

December 13, 2024 data cutoff

Differentiated

Safety and

Tolerability

Profile

Encouraging

Clinical Activity

Observed in Post-

Topo-1 TNBC;

Expansion

Initiated

Potential for Even Greater Clinical Activity in High Dose Range

1. Bardia et al. NEJM 2021 April 22; 384(16): 1529-1541

ADC, antibody-drug conjugate; mg/m2, milligrams per meter squared; ORR, objective response rate per RECIST version 1.1; PD-(L)1, programmed cell death ligand 1; PFS, progression-free survival; PRs, partial responses; Q4W, dosing6 every four weeks; TNBC, triple-negative breast cancer; topo-1, topoisomerase-1 inhibitor; TRAEs, treatment-related adverse events; ILD, interstitial lung disease

Trial Design and Demographics

Emi-Le Phase 1 Dose Escalation Design

Dose Escalation (DES)

Primary Endpoints

MTD, safety and tolerability

Secondary Endpoints

ORR, DOR, DCR, PK, ADA

Indications Being Enrolled Include:

Triple-Negative Breast Cancer

HR+ Breast Cancer

Endometrial Cancer

Ovarian Cancer

Adenoid Cystic Carcinoma - Type 1

Backfill Cohorts

Primary Endpoint

Safety and tolerability

Secondary Endpoints

ORR, DOR, DCR, PK, ADA

B7-H4 expression being assessed retrospectively based on fresh or archived tissue to inform biomarker strategy; investigating dose levels and schedules in parallel escalation and backfill cohorts to optimize profile for expansion

ADA, anti-drug antibody; DCR, disease control rate; DOR, duration of response; HR+, hormone-receptor-positive, human epidermal growth factor receptor 2 negative breast cancer; MTD, maximum tolerated dose; ORR, objective response

rate per RECIST version 1.1; PK, pharmacokinetics; RP2D, recommended Phase 2 dose

Phase 1 Dose Escalation and Backfill Enrollment

Broad range of doses and multiple dosing schedules investigated

Doses and Schedules Investigated (in mg/m2 per cycle)

115.0 (n=3)

High

95.0 (n=5)

Dose Range

44.5x2 (n=10)1

~2 mg/kg per cycle

80.0 (n=11)

38.1x2 (n=9)

67.4 (n=4)

67.4 (n=15)

59.0 (n=14)

Intermediate

28.7x2 (n=3)

Dose Range

50.7 (n=14)

44.5 (n=8)

~1 mg/kg per cycle

38.1 (n=6)

38.1 (n=12)

28.7 (n=6)

28.7 (n=3)

Subtherapeutic 21.6 (n=3)

Dose Range

14.4 (n=3)

Q3W

Q4W

7.2 (n=1)

Initial dose selected for expansion

D1+8 Q4W

1. Includes four patients who were enrolled to receive this starting dose and a pre-specified modified dose following cycle 1

Q3W, dosing once every three weeks; Q4W, dosing once every four weeks; AST, aspartate aminotransferase; D1+8 Q4W, dosing on days one and eight every four weeks; DLT, dose-limiting toxicity; mg/kg, milligrams per kilogram; mg/m2, milligrams

per meter squared; TNBC, triple-negative breast cancer; topo-1, topoisomerase-1 inhibitor

Dose Escalation and Backfill Demographics

Majority of patients had breast cancer and received ≥1 prior topo-1 ADC

December 13, 2024 data cutoff

TNBC1

HR+/HER2- BC

Ovarian

Endometrial

ACC-I

Total

(N=63)

(N=34)

(N=14)

(N=12)

(N=7)

(N=130)

Median age

Median prior lines (range)

4 (2-9)

7 (2-15)

5 (2-11)

2.5 (1-4)

0 (0-3)

4.5 (0-15)

Prior topo-1 ADCs received, n (%)

Prior trastuzumab deruxtecan

21 (33.3%)

15 (44.1%)

36 (27.7%)

Prior sacituzumab govitecan

54 (85.7%)

15 (44.1%)

69 (53.1%)

Prior both

17 (27.0%)

10 (29.4%)

27 (20.8%)

Prior either

58 (92.1%)

20 (58.8%)

78 (60.0%)

B7-H4 expression, n (%)

TPS status known

49 (77.8%)

27 (79.4%)

13 (92.9%)

10 (83.3%)

4 (57.1%)

103 (79.2%)

High (TPS ≥70)2

22 (44.9%)

8 (29.6%)

7 (53.8%)

5 (50.0%)

3 (75.0%)

45 (43.7%)

Low (TPS <70)

27 (55.1%)

19 (70.4%)

6 (46.2%)

5 (50.0%)

1 (25.0%)

58 (56.3%)

TPS not yet determined

14 (22.2%)

7 (20.6%)

1 (7.1%)

2 (16.7%)

3 (42.9%)

27 (20.8%)

ACC-1, adenoid cystic carcinoma - type 1; ADC, antibody-drug conjugate; HR+/HER2- BC, hormone-receptor-positive, human epidermal growth factor receptor 2 negative breast cancer; TNBC, triple-negative breast cancer; topo-1,

topoisomerase-1 inhibitor; TPS, tumor proportion score

Safety and Tolerability

Disclaimer

Mersana Therapeutics Inc. published this content on January 10, 2025, and is solely responsible for the information contained herein. Distributed by Public, unedited and unaltered, on January 10, 2025 at 14:21:03.366.