Our services

ADC Review
is made possible by:




PEER-REVIEWED ARTICLES

Mersana Therapeutics Focuses its Resources on Advancing XMT-1536, its First-in-Class ADC Candidate Targeting NaPi2b

Mersana Therapeutics, a clinical-stage biopharmaceutical company developing a pipeline of antibody-drug conjugates or ADCs designed to target cancers in areas of high unmet need, confirmed that, after a strategic evaluation, the company and its partner Takeda, will discontinue the development of XMT-1522, a  antibody-drug conjugate targeting HER2-expressing tumors, including patients with advanced HER2-positive breast and gastric cancer, as well as advanced breast cancer with low HER2 expression and non-small cell lung cancer (NSCLC).

XMT-1522 contains a proprietary HER2 antibody which is conjugated with Mersana’s Dolaflexin® platform – a Fleximer polymer linked with a novel, proprietary, auristatin payload. The investigational agent provides a drug load of approximately 12 molecules per antibody, specifically designed to improve potency while simultaneously increasing tolerability.

In a statement, the company confirmed that it will work with investigators to ensure that patients benefiting from XMT-1522 will continue to have access to the therapy as needed.

“On behalf of the Company and our partner Takeda we want to thank the patients and their families for their participation in the study, as well as the investigators and our team for their diligent work on the clinical development of XMT-1522. We are committed to leveraging our proprietary ADC platforms to generate a differentiated pipeline of ADCs,”  said Dirk Huebner, MD, Chief Medical Officer, Mersana Therapeutics.

XMT-1536
Following strategic evaluation, Mersana will focus its resources on the advancement of XMT-1536, a first-in-class ADC candidate targeting NaPi2b.

“While still in early clinical development, we are encouraged with the safety, tolerability, and activity of XMT-1536 as well as the pace at which the current study is advancing. For this reason, we have decided to focus our resources on advancing XMT-1536, our first-in-class ADC candidate targeting NaPi2b, a clinically validated ADC target broadly expressed in ovarian and NSCLC adenocarcinoma, for which there remains a significant unmet medical need,” explained Anna Protopapas, President and CEO, Mersana Therapeutics.

According to Protopapas, XMT-1536 has the potential to play a significant role in the treatment of these diseases. The shift in focus resulted in the discontinuation of the XMT-1522 development program.

“We have made the difficult decision to terminate the further development of XMT-1522 despite a favorable emerging profile of efficacy and tolerability due to the competitive environment for HER2-targeted therapies,” Protopapas added.

Dose escalation study
The data to date from the ongoing XMT-1536 dose escalation study indicate that the trial has reached clinically relevant dose levels but has not yet reached a maximum tolerated dose. The once-every-three-week regimen has been fully explored.  The once-every-four-week schedule is currently being evaluated.  The 20 mg/m2 dose cohort has been shown to be well tolerated and the 30 mg/m2 is currently being evaluated.

As of December 31, 2018, the dose escalation study of XMT-1536, in multiple tumor types, includes eight heavily pretreated and evaluable ovarian cancer patients treated at clinically relevant doses. These patients are unselected for NaPi2b expression and had 3 to 11 (median 6) prior regimens in the platinum resistant or refractory setting. Of these eight patients, two achieved a partial response and the remaining six achieved stable disease. The higher dose levels currently being evaluated, as well as additional patient enrollment, provide the opportunity to further define and optimize the profile of XMT-1536.

Corporate Goals
Mersana expects to select a dose for use in its Phase I expansion studies and to initiate enrollment of patients in the expansion cohorts in the first half of 2019. The expansion cohorts will focus on platinum-resistant ovarian cancer and NSCLC adenocarcinoma. Mersana also plans to utilize its proprietary and validated immunohistochemistry assay to retrospectively determine NaPi2b expression to determine whether a companion diagnostic would facilitate the clinical development of XMT-1536. Mersana also plans to report Phase I dose escalation data in the first half of 2019.

Pipeline Expansion
The Company expects to disclose its next clinical candidate in the second half of 2019 and is targeting the filing of an Investigational New Drug (IND) application with the U.S. Food and Drug Administration (FDA) in the first half of 2020.

Research and Discovery
Mersana continues to build a pipeline of promising ADCs across a variety of tumor types with significant unmet need, leveraging its three proprietary ADC platforms (Dolaflexin, Dolasynthen, and Alkymer).

Based on the strategic evaluation, Mersana will apply its expertise in ADCs to optimize and validate Immunosynthen, a new platform designed to allow systemic delivery of a potent immunostimulatory molecule to provide optimal efficacy and tolerability.

Collaboration
This week Mersana and Synaffix, a Dutch biotechnology company, confirmed that the two companies have entered into a license agreement in which Mersana gets access to Synaffix’s industry-leading site-specific GlycoConnect™ ADC technology.

“After evaluating several site-specific conjugation platforms, we have chosen Synaffix’s GlycoConnect™ technology for use in future ADC candidates,” Protopapas explained.

“We are excited about the potential of this technology as it is designed not to require additional antibody engineering or cell-line modifications, which would offer us the potential to create site-specific antibodies for use in our ADCs when required,” she concluded.


Last Editorial Review: January 4, 2019

Featured Image: Details of medical laboratory | microscope. Courtesy: © 2017 – 2019. Fotolia Used with permission.

Copyright © 2013 – 2019 InPress Media Group. All rights reserved. Republication or redistribution of InPress Media Group content, including by framing or similar means, is expressly prohibited without the prior written consent of InPress Media Group. InPress Media Group shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. ADC Review / Journal of Antibody-drug Conjugates is a registered trademarks and trademarks of InPress Media Group around the world.

Share

XMT-1522 Trial in Progress Data Presented at ASCO

Data from a trials in progress abstract presented during the 2017 annual meeting of the American Society of Clinical Oncology (ASCO) confirmed the continued advancement of Mersana Therapeutics Phase I clinical trial of XMT-1522.

Mersana is a clinical-stage biotechnology company focused on discovering and developing a pipeline of antibody-drug conjugates or ADCs based on the company’s proprietary Dolaflexin® platform with DolaLock payload technology.

XMT-1522 is an antibody-drug conjugate or ADC consisting of a novel human IgG1 anti-HER2 monoclonal antibody conjugated to a proprietary auristatin-based cytotoxic payload.

An average of 12 auristatin-based cytotoxic payload molecules are, via a biodegradable polymer, conjugated to each antibody .

In October, 2016, U.S. Food and Drug Administration (FDA) cleared Mersana’s Investigational New Drug (IND) application to begin Phase I clinical trials for XMT-1522, which is the company’s first pipeline product, and could define a new class of HER2-targeted therapies.

Clinical trial
The Phase Ib trial is an open label, multi-center study of XMT-1522 administered as an intravenous infusion once every three weeks.

The dose escalation part of the study is designed to help establish the maximum tolerated dose or recommended Phase II dose for in patients with advanced breast cancer and either a HER2 immunohistochemistry (IHC) score of at least 1+ using a validated IHC assay or with evidence of HER2 amplification.

Patients with HER2 positive (by IHC or amplification) gastric cancer or nonsmall cell lung cancer may also be eligible for participation in the dose escalation part of the trial. Upon completion of dose escalation, the cohort expansion segment of the study is designed to consist of four parallel cohorts of different patients groups to confirm the maximum tolerated dose or the recommended Phase II dose and estimate the objective response in each of the patient populations.

Photo 1.0: Donald A. Bergstrom, M.D., Ph.D., Chief Medical Officer, Mersana Therapeutics.

“The clinical experience with XMT-1522 to date has been consistent with the promising preclinical data,” noted Donald A. Bergstrom, M.D., Ph.D., Chief Medical Officer, Mersana Therapeutics.

“We look forward to providing interim Phase I results for XMT-1522 at a scientific conference later in 2017 as well as beginning clinical trials in Q1 2018 with XMT-1536, our second Dolaflexin ADC.”

“We anticipate that the Phase I data for these two assets will establish the potential of the Dolaflexin ADC platform to generate products that bring meaningful clinical benefit to patients,” Bergstrom cocluded.


Last editorial review: June 5, 2017

Featured Image: Laboratory glassware for science research. Courtesy: © 2017. Fotolia. Used with permission.

Copyright © 2017 InPress Media Group, LLC. All rights reserved. Republication or redistribution of InPress Media Group content, including by framing or similar means, is expressly prohibited without the prior written consent of InPress Media Group. InPress Media Group shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. ADC Review / Journal of Antibody-drug Conjugates is a registered trademarks and trademarks of InPress Media Group around the world.

Share

XMT-1536 Demonstrates Anti-Cancer Activity in Patients with NaPi2b-expressing Tumors

Preclinical data for Mersana Therapeutics‘ new immunoconjugate product candidate, XMT-1536, demonstrated significant anti-cancer activity in non-small cell lung cancer (NSCLC) and ovarian cancer tumor models.

The data presented during a poster session at annual meeting of the American Association for Cancer Research (AACR) being held April 16 – 20 in New Orleans, LA, shows that XMT-1536 is a highly potent anti-sodium-dependent phosphate transport protein 2B (anti-NaPi2b) immunoconjugate or antibody-drug conjugate (ADC) comprised of an average of 15 monomethyl auristatin E (MMAE) molecules conjugated to XMT-1535, a novel humanized anti-NaPi2b antibody, via Mersana’s Dolaflexin™ ADC- platform. Dolaflexin is one of Mersana’s proprietary Fleximer® immunoconjugate platforms.

IND-enabling studies
We are encouraged by the durable regressions XMT-1536 achieved in non-small cell lung cancer and ovarian cancer tumor models, as well as the excellent tolerability and pharmacokinetics in non-human primate exploratory toxicology studies,” noted Donald A. Bergstrom, MD, PhD, Chief Medical Officer of Mersana.

“Based on these data, we are advancing XMT-1536 into IND-enabling studies for the treatment of patients with NaPi2b-expressing tumors,” Bergstrom continued.

NaPi2b expression
The study evaluated XMT-1536 in non-squamous NSCLC and non-mucinous ovarian cancer tumor models, indications in which NaPi2b is highly expressed. XMT-1536 demonstrated significant efficacy in all four patient-derived xenograft models representative of the target patient populations. In three patient-derived models of NSCLC, including KRAS-mutant NSCLC, XMT-1536 induced tumor regressions after three weekly doses of 3 mg/kg.

In an ovarian cancer xenograft model, XMT-1536 induced partial tumor regressions after a single dose of 3 mg/kg, and complete tumor regressions after a single dose of 5 mg/kg or three weekly doses of 3 mg/kg. XMT-1536 was well-tolerated with no evidence of bone marrow toxicity in non-human primates at up to seven times the dose associated with tumor regression in the mouse xenograft models.

“XMT-1536 further validates the ability of Mersana’s Fleximer platform to generate targeted therapies that have the potential to address unmet needs and improve outcomes for patients with cancer. While there have been recent advancements in the treatment of non-small cell lung cancer and ovarian cancer, there remains tremendous need to address the significant proportion of patients who do not derive full benefit from currently available treatments,” Anna Protopapas, President and Chief Executive Officer of Mersana, explained.

“We look forward to the continued development of this second product candidate in our growing pipeline of Fleximer-based immunoconjugate therapies, as we prepare to enter the clinic with XMT-1522 this year,” she continued.

XMT-1536 has the potential to address significant unmet needs and improve patient outcomes in multiple oncology indications. The Fleximer-based immunoconjugate molecules have been shown to have superior efficacy, including with targets previously considered not amenable to antibody-drug conjugate approaches.


Last Editorial Review: April 18, 2016

Featured Image: Inside the Ernest N. Morial Convention Center in New Orleans, LA.  Courtesy: © Sunvalley Communication/Evan Wendt. Used with permission. Logo: © AACR/Used with permission.

Copyright © 2016 InPress Media Group. All rights reserved. Republication or redistribution of InPress Media Group content, including by framing or similar means, is expressly prohibited without the prior written consent of InPress Media Group. InPress Media Group shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. ADC Review / Journal of Antibody-drug Conjugates is a registered trademarks and trademarks of InPress Media Group around the world.

Share

XMT-1522 Continues to Demonstrate Complete Tumor Regressions in Multiple HER2-Expressing Breast Cancer Tumor Models

Positive preclinical data for Mersana Therapeutics‘  lead product candidate, XMT-1522, demonstrates significant anti-cancer activity in both HER2-positive and HER2 low-expressing tumor models refractory to currently available therapies. The new data were presented today during a poster session at the 2015 San Antonio Breast Cancer Symposium (SABCS) being held December 8 – 12, 2015 in San Antonio, Texas.[1]

XMT-1522 is an anti-HER2 antibody-drug conjugate or ADC comprised of a novel anti-HER2 antibody (HT-19) and the dolaflexin ADC platform.  The technology allows for conjugation of 12-15 proprietary auristatin drug payload molecules per antibody without aggregation or detrimental impact on pharmacokinetics.

The anti-HER2 HT-19 antibody binds to a novel HER2 extracellular domain epitope. Studies have shown that the HT-19 antibody does not compete for HER2 binding with trastuzumab (Herceptin®; Genentech/Roche) or or pertuzumab (Perjeta®; Genentech/Roche). Consequently, the combination of XMT-1522 with trastuzumab does not block the ability of the ADC to bind HER2 or efficiently internalize.  Researchers found that in vivo the combination of low dose XMT-1522 with a full dose trastuzumab and pertuzumab is synergistic in a HER2-driven model.

In in vitro researchers found that XMT-1522 has sub-nanomolar potency in cell lines expressing as few as 25,000 HER2 antigens per cell, and is ∼100X more potent than ado-trastuzumab emtansine (Kadcyla®‎; Genentech/Roche) across a panel of 25 cell lines representing a range of tumor indications and HER2 expression levels.

The drug candidate pairs Mersana’s Fleximer® immunoconjugate polymer backbone with the company’s custom linker chemistries to create ADC therapies armed with high doses of a proprietary derivative of the dolastatin family of cytotoxic agents.

The conjugate, optimized for payload delivery, utilizes a novel HER2-targeted antibody, which binds to a different epitope than existing anti-HER2 antibodies. XMT-1522 has the potential to address significant unmet needs and improve patient outcomes in multiple oncology indications.

Superior efficacy
Fleximer-based immunoconjugate molecules have been shown to have superior efficacy, including with targets previously considered not amenable to antibody-drug conjugate approaches. Mersana has collaborations utilizing Fleximer technology with Takeda, Merck KGaA, and Asana BioSciences.

Study
The study evaluated XMT-1522 in models of HER2 low-expressing (IHC 1+/2+) advanced breast cancer, and HER2-positive breast cancer insensitive to ado-trastuzumab emtansine and other HER2-targeted therapies.

“These results demonstrate XMT-1522’s potential to expand the population of breast cancer patients for whom HER2-targeted therapy is appropriate, from the 20 percent currently diagnosed with HER2-positive breast cancer to the full range of patients with HER2 expression,” noted Donald A. Bergstrom, M.D., Ph.D., Chief Medical Officer of Mersana.

“The data strongly support moving XMT-1522 into clinical trials with breast cancer patients who have both HER2-positive and HER2 low-expressing tumors,” Bergstrom added.

The study showed significant efficacy of XMT-1522 in all eight xenograft models representative of the target patient populations. In three HER2-positive models, XMT-1522 dosed at 1 mg/kg or 3 mg/kg induced durable complete tumor regressions, while currently available HER2-targeted therapies, including ado-trastuzumab emtansine or lapatinib (Tykerb®; Novartis) /gemcitabine (Gemzar®; Eli Lilly and Company) were inactive.

In five patient-derived xenograft models of HER2 low-expressing breast cancer, a 1 mg/kg or 3 mg/kg XMT-1522 dose led to complete tumor regression in three of the five models, with tumor stasis in the remaining two models. All models achieving complete regression were refractory to gemcitabine, a standard agent for advanced breast cancer patients with HER2-negative disease. The doses of XMT-1522 associated with tumor regression in these models have previously been shown to be well-tolerated in non-human primate safety studies.

The exposure achieved with XMT-1522 at well-tolerated doses in cynomolgus monkey is several fold higher than the exposure needed in mice to achieve complete tumor regressions across models representing a range of HER2 expression and tumor indications. Based on these data, XMT-1522 will soon enter clinical testing in breast cancer patients with both HER2-positive tumors and HER2 low-expressing (IHC 1+ and 2+/FISH-) tumors.


Last Editorial Review: December 15, 2015

Featured Image: SABCS 2015 San Antonio Breast Cancer Symposium – Attendees fill the opening Plenary Session, Wednesday December 9, 2015. During the San Antonio Breast Cancer Symposium being held at the Henry B. Gonzalez Convention Center in San Antonio, TX. Over 7,500 physicians, researchers, patient advocates and healthcare professionals from over 90 countries attended the meeting which features the latest research on breast cancer treatment and prevention. Courtesy: © MedMeetingImages/Todd Buchanan 2015. Used with permission.

Copyright © 2015 InPress Media Group. All rights reserved. Republication or redistribution of InPress Media Group content, including by framing or similar means, is expressly prohibited without the prior written consent of InPress Media Group. InPress Media Group shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. ADC Review / Journal of Antibody-drug Conjugates is a registered trademarks and trademarks of InPress Media Group around the world.

Share

Skip to toolbar