Upinitatug rilsodotin, Upifitamab rilsodotin Terminated ADC

Antibody Information

Entry ID	2594
INN	Upinitatug rilsodotin, Upifitamab rilsodotin
Status	Terminated
Drug code(s)	XMT-1536
Brand name	None
mAb sequence source	mAb humanized
General Molecular Category	ADC
Format, general category	Full length Ab conjugate
Format details	None
Isotype (Fc)	IgG1
Light chain isotype	kappa
Linker	Dolaflexin polymer scaffold
Ave. DAR	10 to 15 drugs per mAb
Conjugated/fused moiety	Tubulin inhibitor, Auristatin F-hydroxypropylamide
Discovery method/technology	None

Therapeutic information

Target(s)	NaPi2b
Indications of clinical studies	Ovarian cancer, Cancers Likely to Express NaPi2b
Primary therapeutic area	Cancer

Development stage information

Phase lengths*

*The graph represents early-stage clinical development phase lengths. For molecules approved or under evaluation for marketing authorization in the US is provided a complete overview of all clinical development phase lengths. Phase lengths are calculated from the start of the first in human (FIH) study (Start of clinical phase). “Start of Phase 2” bar represents Phase 1 length (Start of clinical phase to start of Phase 2); “Start of Phase 3” bar represents Phase 1+2 length (Start of clinical phase to start of Phase 3); “Date BLA/NDA submitted” bar represents Phase 1+2+3 length (Start of clinical phase to Date BLA/NDA submitted); and “Date of first US approval” bar represents Phase 1 to first US approval length (Start of clinical phase to Date of first US approval).

Most advanced stage of development (global)	Terminated at Phase 3
Status	Inactive
Start of clinical phase (IND filing or first Phase 1)	December 12, 2017
Start of Phase 2
Start of Phase 3	June 23, 2022
Date BLA/NDA submitted to FDA
Year of first approval (global)	None
Date of first US approval
INN, US product name	None
US or EU approved indications	None

Company information

Company	Mersana Therapeutics Inc.
Licensee/Partner	None
Comments about company or candidate	July 2023: UPLIFT trial did not meet endpoint. Mersana’s restructuring plan includes a wind-down of UpRi-related development activities, including its UP-NEXT and UPGRADE-A clinical trials and the company’s regulatory and commercial readiness efforts. If analyses of data enable the identification of a path forward for UpRi, the company will consider strategic alternatives for the asset, including partnering. June 15, 2023: Mersana Therapeutics, Inc. announced that the U.S. Food and Drug Administration (FDA) has issued a partial clinical hold pausing new patient enrollment in UP-NEXT and UPGRADE-A, the company’s ongoing clinical trials of UpRi in platinum-sensitive ovarian cancer. Mersana’s recent assessment determined that serious bleeding events appear to occur at a higher rate than background. While most bleeding cases in this aggregate safety analysis were low-grade, five (<1%) Grade 5 (fatal) bleeding events were observed among the approximately 560 patients dosed to date. The causes of bleeding events remain under investigation. Dec 2022: European Commission (EC) has designated upifitamab rilsodotin (UpRi) as an orphan medicinal product for the treatment of ovarian cancer. NCT05329545 UP-NEXT, a Phase 3 trial of UpRi monotherapy maintenance in platinum-sensitive recurrent ovarian cancer with a design informed by FDA and CHMP feedback, due to start May 26, 2022. NCT04907968 Phase 1/2 in ovarian cancer started in April 2021. Jan 2021: “2021 promises to be another transformative year for Mersana’s pipeline. Our focus will be to initiate the UPLIFT single-arm registration strategy for XMT-1536 in platinum-resistant ovarian cancer and to initiate the UPGRADE combination umbrella study with the goal of informing the path into earlier lines of ovarian cancer therapy. Aug 2020: The FDA granted fast track designation to XMT-1536 for the treatment of women with high-grade serous ovarian cancer, according to a press release from the agent’s manufacturer. Phase 1 study still recruiting as of Aug 2019. Sep 2018: Mersana and the FDA reached alignment on changes to XMT-1522's study protocol, including increased monitoring as well as the exclusion of patients with advanced hepatic impairment. Although XMT-1536, Mersana’s Dolaflexin ADC targeting NaPi2b, was not subject to a clinical hold, Mersana has decided to implement similar modifications to the XMT-1536 protocol. Alternative dosing regimens will be evaluated for both clinical trials. NCT03319628 and NCT06517433 are both First-in-Human Studies of XMT-1536 in Cancers Likely to Express NaPi2b started in Dec 2017. XMT-1536 uses Mersana’s proprietary Dolaflexin platform to generate an ADC with a drug to antibody ratio (DAR) of 12-15.
Full address of company	840 Memorial Drive, Cambridge, MA 02139 North America United States of America https://www.mersana.com/contact/

Description/comment

XMT-1536 is a highly potent immunoconjugate targeting the sodium-dependent phosphate transport protein (NaPi2b) and is comprised of an average of 10-15 DolaLockTM payload molecules conjugated to XMT-1535, a proprietary humanized anti-NaPi2b antibody, via the Dolaflexin ADC platform. NaPi2b is an antigen highly expressed in the majority of non-squamous NSCLC and epithelial ovarian cancer.
https://www.gog.org/wp-content/uploads/2021/04/04-ADC-Napi2b-as-the-Target-Presentation.pdf

Additional information

Anticipated events	None
Factor(s) contributing to discontinuation	None