XMT-1592 / Mersana, Recepta - LARVOL DELTA

The impact of scaffold, linker, homogeneity and payload selection on the efficacy and tolerability of anti-tubulin ADCs (AACR 2024) - "Two anti-NaPi2b ADCs were produced using two different platforms, XMT-1536 (Dolaflexin platform) and XMT-1592 (Dolasynthen platform), conjugated to the same antibody and employing the same payload. The Dolasynthen platform was deliberately designed, taking into account preclinical and clinical learnings from earlier ADC platforms, to improve both safety and efficacy. In addition, comparisons to clinically approved anti-tubulin ADC platforms are made to provide further context."

Clinical • Oncology • SLC34A2

First-in-Human Study of XMT-1592 in Patients With Ovarian Cancer and NSCLC Likely to Express NaPi2b (clinicaltrials.gov) - P1 | N=31 | Terminated | Sponsor: Mersana Therapeutics | Phase classification: P1b ➔ P1

Phase classification • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • SLC34A2

Results From The Phase 1 Dose Escalation Study Of XMT-1592, A Dolasynthen NaPi2b-Directed Antibody-Drug Conjugate (ADC) (ESGO 2024) - "ILD/pneumonitis was the most common TRAE and was consistent with preclinical findings that suggest this observation is likely “on target,” relating to NaPi2b expression in type II pneumocytes. While development of this product candidate has been discontinued by the sponsor due to portfolio reprioritization considerations, alternative dosing regimens may warrant further evaluation given the observed activity."

P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • SLC34A2

Mersana Therapeutics Provides Business Update and Announces Fourth Quarter and Full Year 2023 Financial Results (GlobeNewswire) - "At the European Society of Gynaecological Oncology (ESGO) 2024 Congress from March 7-10, 2024 in Barcelona, Spain, clinical data will be presented for Mersana’s two discontinued NaPi2b ADC product candidates: XMT-1536 (UpRi), which was developed using the company’s first-generation Dolaflexin ADC platform, and XMT-1592, which was developed using the company’s next-generation Dolasynthen ADC platform....The decline in R&D expenses was primarily related to reduced manufacturing and clinical costs related to UpRi and XMT-2056 and manufacturing costs for the company’s Dolasynthen platform, partially offset by increased clinical costs related to XMT-1660."

Clinical data • Commercial • Oncology • Solid Tumor

Mersana Therapeutics Announces Business Updates, Expected 2024 Milestones and Upcoming Presentation at the 42nd Annual J.P. Morgan Healthcare Conference (GlobeNewswire) - "XMT-1660: Mersana continues to advance its Phase 1 clinical trial of XMT-1660, the company’s lead Dolasynthen ADC candidate targeting B7-H4...Mersana plans to initiate tumor-specific expansion cohorts in the second quarter of 2024 and share initial dose escalation and backfill cohort data in mid-2024...XMT-2056: Mersana is restarting its Phase 1 clinical trial of XMT-2056...The company plans to advance dose escalation in 2024....In the first half of 2024, Mersana expects to present data at multiple scientific meetings demonstrating Dolasynthen’s differentiation from first-generation cytotoxic ADC platforms. The presentations will include clinical data from two discontinued ADC candidates, XMT-1592 and XMT-1536 (UpRi)."

Clinical data • P1 data • Trial status • Oncology • Solid Tumor

First-in-Human Study of XMT-1592 in Patients With Ovarian Cancer and NSCLC Likely to Express NaPi2b (clinicaltrials.gov) - P1b | N=31 | Terminated | Sponsor: Mersana Therapeutics | N=120 ➔ 31 | Active, not recruiting ➔ Terminated; discontinued development program

Enrollment change • Trial termination • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • SLC34A2

First-in-Human Study of XMT-1592 in Patients With Ovarian Cancer and NSCLC Likely to Express NaPi2b (clinicaltrials.gov) - P1b | N=120 | Active, not recruiting | Sponsor: Mersana Therapeutics | Trial primary completion date: Dec 2022 ➔ Mar 2023

Trial primary completion date • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • SLC34A2

First-in-Human Study of XMT-1592 in Patients With Ovarian Cancer and NSCLC Likely to Express NaPi2b (clinicaltrials.gov) - P1b | N=120 | Active, not recruiting | Sponsor: Mersana Therapeutics | Recruiting ➔ Active, not recruiting

Enrollment closed • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • SLC34A2

Mersana Therapeutics Announces 2022 Strategic Priorities and Milestones (GlobeNewswire) - "XMT-1592, a first Dolasynthen ADC targeting NaPi2b, is currently in a Phase 1 trial, with dose exploration expected to be complete in the second half of 2022....XMT-1660, a first-in-class Dolasynthen ADC targeting B7-H4, is expected to initiate a Phase 1 dose escalation trial in mid-2022....XMT-2056, a first-in-class HER2-targeted Immunosynthen STING-agonist ADC, is expected to initiate a Phase 1 dose escalation trial in mid-2022....The Company plans to disclose two new development candidates, XMT-2068 and XMT-2175, during the first half of 2022....The Company will review these corporate updates and milestones during its upcoming presentation at the upcoming virtual 40th Annual J.P. Morgan Healthcare Conference on Wednesday, January 12, 2022 at 3:00 pm ET."

Clinical • New P1 trial • Trial completion date • Oncology

Synaffix Announces Expansion of Mersana License Deal to a Total Potential Value Exceeding $1 Billion (PRNewswire) - “Synaffix B.V….announces the expansion of its license agreement with Mersana Therapeutics, Inc. Under the expanded license agreement, Mersana will expand its access to Synaffix's GlycoConnect™ site-specific ADC bioconjugation technology for six additional ADC targets. The license rights granted to Mersana are tied to specific ADC targets to be selected and provide non-exclusive access to deploy GlycoConnect™ site-specific ADC bioconjugation technology against the specified targets. Under the expanded deal, Synaffix is eligible to receive upfront and milestone payments on a per-target basis with a total potential deal value exceeding $1 billion plus royalties. This builds on the long-term relationship between the two companies announced in 2019….This licensing agreement expansion follows three recent ADC technology out-licensing agreements with Kyowa Kirin,…ProfoundBio…Innovent Biologics….”

Licensing / partnership • Oncology

Mersana Therapeutics Announces Third Quarter 2021 Financial Results and Provides Business Update (GlobeNewswire) - "Introduced UP-NEXT, a Phase 3 study of UpRi monotherapy maintenance, informed by FDA feedback: The Company plans to provide more details on the final design of UP-NEXT and expects to initiate the study in 2022; UPLIFT, a single-arm registration study in platinum-resistant ovarian cancer, continues to enroll: The Company plans to enroll approximately 100 patients with high NaPi2b expression and up to 180 patients overall and expects the study to be substantially enrolled during the summer of 2022; Phase 1 dose escalation study of XMT-1592 is ongoing. The Company continues dose exploration in order to determine the recommended Phase 2 dose and expects this to continue into 2022. The Company plans to provide further details of the XMT-1592 development plan alongside its 2022 milestones and goals early next year."

Clinical data • Enrollment status • IND • Gynecologic Cancers • Oncology • Ovarian Cancer

[VIRTUAL] Early Phase Fit-for-Purpose Process Development of XMT-1592 Against Accelerated Timelines (ADC-USA 2021) - "Sharing a rapid tech transfer and process development strategy Exploring QbD-based optimization of conjugation unit operation Assessing development of HIC purification"

[VIRTUAL] Delving into XMT-1660, XMT-1592 & the Dolasynthen Platform (ADC-USA 2021) - "Synopsis Outlining how the Dolasynthen platform is a fully homogeneous, defined platform compatible with multiple site specific bioconjugation technologies Highlighting the opportunity Dolasynthen provides to precisely create ADCs with DARs ranging from 2 to 18+ with full homogeneity Providing details on the Dolasynthen ADCs XMT-1660 targeting B7H4 and XMT-1592, targeting NaPi2b"

SLC34A2

Sodium-dependent phosphate transporter NaPi2b as a potential predictive marker for targeted therapy of ovarian cancer. (PubMed, Biochem Biophys Rep) - "The sodium-dependent phosphate transporter NaPi2b encoded by SLC34A2 gene is expressed in 80-90% of epithelial ovarian cancers and used as a target for therapeutic antibodies XMT-1536, and XMT-1592, which are derived from MX35 antibodies and used in clinical trials for the treatment of ovarian and lung cancers. In this work, we demonstrated that the expression of the human NaPi2b (hNaPi2b) transporter is downregulated in the tumors of patients receiving neoadjuvant therapy and during the development of disease. The data suggest that the level of expression of the SLC34A2 gene can serve as a potential marker for the monitoring and predicting responses to neoadjuvant and targeted therapy in patients with ovarian cancer."

Biomarker • Journal • Developmental Disorders • Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • SLC34A2

Mersana Therapeutics Announces Second Quarter 2021 Financial Results and Provides Business Update (GlobeNewswire) - “Upifitamab Rilsodotin: The Company expects to provide an update on the ovarian cancer expansion cohort this year; NSCLC adenocarcinoma cohort of the expansion portion of Phase 1 study continues to enroll patients. The Company is on track to enroll approximately 45 patients in the expansion phase of the study. The Company plans to disclose top-line data and determine next steps in this indication in the fourth quarter of 2021; XMT-1592: The Company plans to disclose top-line data and outline the development plan in NSCLC adenocarcinoma around the end of the year.”

P1 data • P1/2 data • Trial status • Gynecologic Cancers • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer

First-in-Human Study of XMT-1592 in Patients With Ovarian Cancer and NSCLC Likely to Express NaPi2b (clinicaltrials.gov) - P1b; N=120; Recruiting; Sponsor: Mersana Therapeutics; Trial completion date: Dec 2021 ➔ Jun 2023; Trial primary completion date: Mar 2021 ➔ Dec 2022

Clinical • Trial completion date • Trial primary completion date • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • SLC34A2

Mersana Therapeutics Announces Fourth Quarter and Full Year 2020 Financial Results and Provides Business Update (GlobeNewswire) - “…Anticipated Milestones: XMT-1592, first Dolasynthen ADC targeting NaPi2b: The Company continues dose escalation and plans to disclose interim data in the second half of 2021 and outline the XMT-1592 development plan in NSCLC in the fourth quarter of 2021; XMT-1660, first-in-class Dolasynthen ADC targeting B7-H4: The Company plans to initiate a Phase 1 dose escalation study of XMT-1660 in early 2022; XMT-2056, first Immunosynthen STING-agonist ADC: The Company plans to disclose the target for this program in the fourth quarter of 2021 and to initiate a Phase 1 dose escalation study in early 2022; Mersana will present preclinical data for XMT-1660, XMT-2056 and its novel Immunosynthen STING-agonist ADC platform in the e-poster session at the American Association for Cancer Research (AACR) Virtual Annual Meeting scheduled for April 10-15, 2021.”

Clinical • New P1 trial • P1/2 data • Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology

Mersana Therapeutics Announces Corporate and Pipeline Updates and 2021 Goals and Anticipated Milestones (GlobeNewswire) - "XMT-1592: The Company continues to dose escalate and plans to disclose interim dose escalation data in the second half of 2021 and outline the XMT-1592 development plan in the fourth quarter of 2021."

P1 data • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology

Mersana Therapeutics Announces Third Quarter 2020 Financial Results and Provides Business Update (GlobeNewswire) - “Mersana plans to host a virtual Analyst and Investor Day event to provide an update on the ovarian cancer cohort of the XMT-1536 Phase 1 expansion study and the path forward in ovarian cancer around year end…New international sites added to support enrollment of the NSCLC adenocarcinoma patient cohort of the XMT-1536 Phase 1 expansion study…The Company will continue to recruit the expansion cohort and expects to discuss its data disclosure plans for the NSCLC adenocarcinoma patient cohort in early January 2021…The Company continues to dose escalate and expects to discuss its data disclosure plans for XMT-1592 in early January 2021… Mersana on track disclose its first-in-class ADC targeting B7-H4 development candidate and supporting data around year end.”

Clinical • Trial status • Gynecologic Cancers • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer

[VIRTUAL] XMT-1592, a site-specific Dolasynthen-based NaPi2b-targeted antibody-drug conjugate for the treatment of ovarian cancer and lung adenocarcinoma (AACR-II 2020) - "XMT-1592 had improved in vivo activity, pharmacokinetics, and clinical pathology relative to its stochastic counterpart. Taken together, these results support XMT-1592 as a development candidate for the treatment of NaPi2b-expressing tumors."

Gynecologic Cancers • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • Thoracic Cancer • EGFR • KRAS • SLC34A2

Mersana Therapeutics Presents Preclinical Data from its Innovative Dolasynthen and Immunosynthen ADC Platforms at American Association for Cancer Research 2020 Virtual Annual Meeting (GlobeNewswire) - "XMT-1592 shows improved in vivo activity, pharmacokinetics and clinical pathology relative to its stochastic counterpart. These data also show that XMT-1592 induced sustained tumor regressions in an NSCLC adenocarcinoma patient-derived xenograft....The data also show that the STING-agonist ADC was more active (over 100-fold increased potency) with limited induction of systemic cytokines when compared to intravenously administered unconjugated (free) agonist, suggesting it may confer an improved therapeutic index."

Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology

Mersana Therapeutics announces first quarter 2020 financial results and provides business update (GlobeNewswire) - "Upcoming Events: The Company will present interim data from the XMT-1536 Phase 1 expansion study on a live conference call and webcast on Wednesday, May 27, 2020 at 8 a.m. ET and during a poster session at the American Society of Clinical Oncology (ASCO) 2020 Virtual Scientific Program scheduled for May 29 – 31, 2020....Mersana will present preclinical data for XMT-1592 and its novel Immunosynthen STING-agonist ADC platform at the AACR Virtual Annual Meeting scheduled for June 22 – 24, 2020."

P1 data • Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor

Mersana Therapeutics to present two posters at the American Association for Cancer Research 2020 Virtual Annual Meeting (GlobeNewswire) - "Mersana Therapeutics...announced that it will present preclinical data for XMT-1592, its Dolasynthen ADC candidate targeting NaPi2b, and its Immunosynthen STING-agonist ADC platform at the American Association for Cancer Research (AACR) 2020 Virtual Annual Meeting being held from June 22 – June 24, 2020."

Preclinical • Gynecologic Cancers • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer

First-in-Human Study of XMT-1592 in Patients With Ovarian Cancer and NSCLC Likely to Express NaPi2b (clinicaltrials.gov) - P1b; N=120; Recruiting; Sponsor: Mersana Therapeutics

Clinical • New P1 trial • Gynecologic Cancers • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • Thoracic Cancer

Mersana Therapeutics announces initiation of XMT-1592 phase 1 dose escalation study (PRNewswire) - Mersana Therapeutics...announced the initiation of patient dosing in a Phase 1 dose escalation study evaluating XMT-1592, its Dolasynthen ADC targeting NaPi2b. XMT-1592 is the Company’s first clinical candidate created using its new customizable and homogenous Dolasynthen ADC platform....This Phase 1, open-label, dose-escalation study is designed to determine the maximum tolerated dose (MTD) of XMT-1592 in patients with non-small cell lung cancer (NSCLC) adenocarcinoma and ovarian cancer. Upon completion of the dose-escalation portion of the study, the Company will determine the path forward to further assess the safety and activity of XMT-1592 in the expansion portion of the study."

Enrollment open • Oncology