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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

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U.S. FDA Lifts Partial Clinical Hold for Mersana’s XMT-1522

The United States Food and Drug Administration (FDA) has lifted the partial clinical hold on the Phase I study of XMT-1522, a Dolaflexin® Antibody-drug Conjugate (ADC) targeting HER2-expressing tumors being developed by Mersana Therapeutics.

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.

Lower levels of HER2-expression
XMT-1522 has the potential to extend HER2-targeted therapy beyond the current HER2-positive populations into patients with lower levels of HER2 expression. The Phase I protocol will evaluate XMT-1522 in 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). More information on the ongoing Phase 1 clinical trial can be found at clinicaltrials.gov.

Changes to the protocol
Mersana and the FDA reached alignment on changes to the protocol. These changes include increased monitoring as well as the exclusion of patients with advanced hepatic impairment. Although XMT-1536, another investigational agent being developed by Mersana,was not subject to a clinical hold, the company decided to implement similar modifications to the XMT-1536 protocol.

XMT-1536 is Mersana’s highly potent immunoconjugate targeting the sodium-dependent phosphate transport protein (NaPi2b) comprised of an average of 10-15 DolaLock™ payload molecules conjugated to XMT-1535, a proprietary humanized anti-NaPi2b antibody, via the Dolaflexin ADC platform.

In addition to the changes in the protocol, alternative dosing regimens will be evaluated for both clinical trials.

The XMT-1522 trial will begin with a once-every-four-week dose regimen. This dosing regimen has already been implemented in the XMT-1536 trial at previously explored dose levels in order to enable a comparison of relevant doses and their impact on the safety, efficacy and PK profile of the drug candidate. The company may evaluate additional regimens as well. Data on XMT-1536 is expected in the first half of 2019.

“We are excited to resume enrollment on the XMT-1522 trial and to work with investigators to explore the full potential of both promising drug candidates in the solid tumor setting,” said Anna Protopapas, Chief Executive Officer of Mersana.


Last Editorial Review: September 17, 2018

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Copyright © 2017 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.

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FDA Clears Mersana’s IND Application for XMT-1536

Focusing on discovering and developing a pipeline of novel antibody-drug conjugates or ADCs based on its proprietary Dolaflexin® platform, Mersana Therapeutics’ Investigational New Drug (IND) application for XMT-1536, was cleared to begin Phase I clinical trials.

The U.S. Food and Drug Administration (FDA) IND clearance is the second for Mersana’s Novel Dolaflexin ADC platform within the past year.

“We are excited to be moving XMT-1536 into clinical development as a first-in-class and potentially best-in-class ADC against NaPi2b, a target with outstanding properties for ADC development on the Dolaflexin platform,” noted Donald A. Bergstrom, MD, Ph.D, Chief Medical Officer.

“Currently, patients with advanced epithelial ovarian cancer, non-squamous NSCLC and other NaPi2b-expressing tumors have a poor prognosis, and there’s a clear need for better treatment options. We look forward to beginning the clinical investigation of XMT-1536, which has shown promising results in preclinical models,” Bergstrom added.


Mersana’s proprietary auristatin AF-HPA is capable of controlled bystander-effect killing, resulting in efficacy in tumors with heterogeneous antigen expression… it is metabolized intra-tumorally to an active non-permeable metabolite to enable greater systemic tolerability…


Targeting NaPi2b
XMT-1536 is a first-in-class ADC targeting  the transmembrane sodium-phosphate transporter NaPi2ba (SLC34A2) which is a clinically validated ADC target broadly expressed in epithelial ovarian cancer, non-squamous non-small cell lung cancer (NSCLC), as well as a number of other tumor types. [1]

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

The investigational agent is comprised of Mersana’s Dolaflexin platform conjugated to a proprietary NaPi2b antibody. Each antibody molecule carries 10-15 molecules of Mersana’s proprietary DolaLock payload, resulting in a balance of meaningful preclinical efficacy and preclinical tolerability.

Results from exploratory multiple dose toxicology study showed no evidence of significant pulmonary toxicity (primary tissue with NaPi2b expression) and no neutropenia at 2 times the payload dose that induced fatal neutropenia and sepsis in nonclinical studies of Genentech’s NaPi2b vcMMAE (Lifastuzumab vedotin, developed by Genentech using Seattle Genetics vcMMAE platform).

In preclinical studies, XMT-1536 induced greater than 50% median tumor regression in 10/19 (53%) primary patient-derived ovarian cancer xenograft models unselected for NaPi2b protein expression, with 10/12 (83%) tumor responses in NaPi2b-expressing models. In patient-derived NSCLC xenograft models, XMT-1536 achieved durable tumor regressions in 6/9 (75%) tested models.

DolaLock
Mersana’s proprietary auristatin F-HPA (AF-HPA) drug payload promotes potent cell killing upon initial release of the agent. This proprietary payload is specifically designed to control cell killing of the surrounding tumor cells through bystander effect and increase efficacy in the tumor environment and as well as improve systemic tolerability.

However, this payload is further processed in the cell to a metabolite which remains strongly cytotoxic but loses the ability to cross the cell membrane and as a result, becomes trapped and loses bystander capability.

This feature, which Mersana refers to as ‘DolaLock,’ makes it possible to capture the benefits of the bystander effect while minimizing potential toxicities to healthy tissues.

Milestone
“The clearance of this IND, our second in a year, marks an important milestone for the company as we continue to move our novel pipeline of product candidates into the clinic,” said Anna Protopapas, President and Chief Executive Officer of Mersana.

“This achievement is a result of our dedicated employees who are focused on executing on our important mission of creating therapies with meaningful clinical benefit for patients,” she added.


Last Editorial Review: November 1, 2017

Featured Image: Laboratory Glass. Courtesy: © Fotolia. Used with permission.

Copyright © 2017 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.

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Preclinical Data Supports the Development of XMT-1536 in a Broad Population of Patients with Ovarian Cancer

Update data from preclinical studies with XMT-1536, an antibody-drug conjugates or ADC being developed by Mersana Therapeutics targeting NaPi2b, were presented in a poster at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics: Discovery, Biology, and Clinical Applications, held  October 26 – 30, 2017 in the Pennsylvania Convention Center in Philadelphia, Pennsylvania.  was given by Rebecca Mosher, M.D., Executive Director, Translational Medicine, Mersana Therapeutics.[1]

The data confirms that XMT-1536 may offer positive results for patients with ovarian cancer, which ranks, according to the American Cancer Society, fifth in cancer deaths among women, accounting for more deaths than any other cancer of the female reproductive system. A woman’s risk of getting ovarian cancer during her lifetime is about 1 in 75. Overall, a woman’s lifetime chance of dying from ovarian cancer is about 1 in 100.

The American Cancer Society estimates that in the United States in 2017 about 22,440 women will receive a new diagnosis of ovarian cancer. About 14,080 women will die from ovarian cancer.

This means that ovarian cancer represents a major unmet medical need.

Anti-sodium-dependent phosphate transport protein
XMT-1536 is a highly potent anti-sodium-dependent phosphate transport protein (NaPi2b; SLC34A2) immunoconjugate comprised of an average of 10-15 DolaLock 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. XMT-1536 is scheduled to begin Phase I clinical trials in early 2018.


…the data … support … NaPi2b [as an] outstanding target for ADC development … and the Dolaflexin ADC platform allows us to fully exploit the advantages of this … target…


Outstanding target
“The data presented at AACR-NCI-EORTC further support that NaPi2b is an outstanding target for ADC development and that the Dolaflexin ADC platform allows us to fully exploit the advantages of this interesting target,” said Donald Bergstrom, M.D., Ph.D, Chief Medical Officer, Mersana Therapeutics.

“These results in ovarian cancer models are consistent with data we’ve previously presented on the broad activity of XMT-1536 in preclinical models of non-squamous non-small cell lung cancer (NSCLC). We look forward to initiating Phase I testing of XMT-1536 in patients with ovarian cancer, non-squamous NSCLC and other NaPi2b-expressing tumors by early 2018,” he added.

The study revealed that XMT-1536 induced at least a 50% median reduction in tumor volume relative to baseline in 10/19 (53%) primary patient-derived ovarian cancer xenograft models, that were selected for testing without prior knowledge of NaPi2b expression status. The activity of XMT-1536 was comparable in models derived from tumors from treatment-naïve patients as well as models that came from patients with heavily pre-treated tumors.

Target expression
When NaPi2b target expression was evaluated using a proprietary immunohistochemistry (IHC) assay discovered at Mersana in conjunction with XMT-1536, there was an association between NaPi2b IHC H-score and tumor volume change after XMT-1536 treatment. Among tumors with an H-score ≥70, 10/12 (83%) of models achieved 50% or greater reduction in tumor volume after XMT-1536 treatment, vs. 0/7 (0%) models with an H-score ‹70. Applying the same IHC assay to primary human ovarian tumors, 12/20 (60%) tested tumors had an H-score ≥70, indicating the majority of human ovarian tumors express levels of NaPi2b associated with deep regressions in response to XMT-1536 in pre-clinical models.

“We are extremely pleased with the results of this research and the progress the program has made to date,” said Rebecca Mosher, M.D., Executive Director, Translational Medicine, Mersana Therapeutics.

“The data described in the presentation suggest that XMT-1536 could be broadly active in ovarian cancer, and that we may have a diagnostic tool that could further enrich the patient population to enhance clinical benefit,” she further noted.


Last Editorial Review: October 30, 2017

Featured Image: Laboratory glass. Courtesy: © 2017. Fotolia. Used with permission.

Copyright © 2017 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.

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Mersana’s XMT-1536 Demonstrates Anti-tumor Activity in Lung Cancer Patient-Derived Xenograft Studies

Encouraging data from preclinical studies presented at the 2016 IASLC 17th World Conference on Lung Cancer, in Vienna, Austria, suggests that Mersana Therapeutics‘ immunoconjugate XMT-1536 induces durable complete tumor regressions in patient-derived xenograft models of non-small cell lung cancer (NSCLC). Results demonstrating outstanding pharmacokinetics and tolerability in non-human primates was also presented.[1]


…Based on these data, we plan to move rapidly into studies in patients that will help us develop new therapeutic options to treat this devastating disease…


Non-small cell lung cancer is the most common type of lung cancer. About 85% of lung cancers are non-small cell lung cancers. Squamous cell carcinoma, adenocarcinoma, and large cell carcinoma are all subtypes of non-small cell lung cancer. Both small cell and non-small cell lung cancer combined are, according to American Cancer Society, the second most common cancers in both men and women. In men, prostate cancer is more common, while in women breast cancer is more common. About 14% of all new cancers are lung cancers. [2]

The American Cancer Society’s estimates that there will be about 224,390 new cases of lung cancer in the United States in 2016 (117,920 in men and 106,470 in women) and that about 158,080 deaths people will die of the disease (85,920 in men and 72,160 in women). [2]

Lung cancer mainly occurs in older people, on average 2 out of 3 people diagnosed with lung cancer are 65 or older while less than 2% are younger than 45. Statistically, each year, more people die of lung cancer than of colon, breast, and prostate cancers combined. [2]

Early results
“We are encouraged by these early results that demonstrate XMT-1536’s potential in treating patients who have limited treatment options for their lung cancer,” noted Donald A. Bergstrom, M.D., Ph.D., Chief Medical Officer of Mersana.

“The data we presented at the conference suggest that XMT-1536 can induce complete and durable regressions in patient-derived lung cancer models. Based on these data, we plan to move rapidly into studies in patients that will help us develop new therapeutic options to treat this devastating disease.”

The study confirms that NaPi2b is expressed at high levels in a majority of non-squamous non-small cell lung cancers (NSCLC), suggesting it may be an attractive therapeutic target for antibody-drug development in this disease.

Highly potent immunoconjugate
XMT-1536 is a highly potent anti-sodium-dependent phosphate transport protein 2b (anti-NaPi2b) immunoconjugate comprised of an average of 15 auristatin molecules conjugated to XMT-1535, a novel humanized anti-NaPi2b antibody, via the Dolaflexin™ antibody-drug conjugate (ADC) platform. Dolaflexin is one of Mersana’s proprietary multivalent hydrophilic polymer (Fleximer®) immunoconjugate platforms.

Mersana’s technology platforms allows for significantly higher drug loads, providing greater efficacy while simultaneously increasing tolerability. The anti-tumor activity of XMT-1536 was evaluated in eight patient-derived xenograft models of NSCLC adenocarcinoma representing a spectrum of oncogenic driver mutations prevalent in NSCLC, including tumors without oncogenic drivers.

Trial design
The standard dose of XMT-1536 used across models was 3 mg/kg administered intravenously once weekly for 3 weeks (last dose on Day 14). Experiments ran until tumor growth past a pre-specified endpoint or Day 60. At the 3 mg/kg dose, XMT-1536 was active in 7/8 models: complete tumor regression in 4 models, partial tumor regression in 1 model, and significant tumor growth inhibition in 2 models. In 4 of the 5 models where XMT-1536 induced tumor regression, regressions were durable, with a majority of the animals maintaining partial or complete regression at Day 60.

Non-human primates
XMT-1536 was also evaluated for tolerability in a cynomolgus monkey study, in which there was no body weight loss, no clinical observations attributable to XMT-1536, and limited clinical pathology findings, including no evidence of neutropenia. Target organ toxicity was minimal to mild and generally reversible. Exposure to XMT-1536 indicated good conjugate stability, low exposure to free drug payload in plasma (<1 ng/mL), and supported the 3 mg/kg dose level in mouse studies as a potentially clinically-relevant dose.


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Best ADC Platform Technology Awarded to Mersana Therapeutics

This week, during the 7th World ADC Conference in San Diengo, Mersana Therapeutics, a biotechnology company focused on discovering and developing a pipeline of antibody-drug conjugates or ADCs based on its proprietary Dolaflexin® technology, received “Best ADC Platform Technology” award for its Dolaflexin platform.

Now in their third year, the World ADC Awards are designed to showcase excellence within antibody drug conjugate research. The awards reward the innovation, leadership, and devotion shown by the best companies, teams, and individuals in the industry. Across eight categories the the organizers of the event recognize the extraordinary endeavours, teamwork and commercial acumen that has propelled the field to the forefront of cancer research today.

Mersana was also selected as a runner-up in the “New Drug Developer” category.


“Receiving this award underscores the scientific innovation of Mersana’s Discovery team and potential of …[the] Dolaflexin platform…”


The 7th World ADC’s “Best ADC Platform Technology” award acknowledges the best linker or payload platform technology and is selected for the system’s novelty and originality as well as scientific and commercial validation of the platform.  In addition, the “New Drug Developer” class, recognizes an emerging company involved in the (early) development of antibody-drug conjugates that it has made significant progress within its preclinical pipeline with at least one pipeline drug.

Dolaflexin Platform
Dolaflexin, Mersana’s lead platform technology, is based on the company’s Fleximer polymer backbone and a proprietary aurastatin payload. Fleximer allows for significantly higher DAR (Drug to Antibody Ratio) or payload per antibody (>15) than other ADC approaches resulting in higher efficacy. Furthermore, Fleximer-based immunoconjugate molecules have been shown to have superior efficacy, including with targets previously considered not amenable to antibody-drug conjugate approaches.

The proprietary auristatin payload is designed to be highly potent when released in the tumor cell but to subsequently be metabolized into less potent agent hence resulting in improved tolerability. In early and pre-clinical studies Dolaflexin based ADCs have been shown to be highly efficacious while maintaining a wider therapeutic index than traditional ADCs approaches.

“Receiving this award underscores the scientific innovation of Mersana’s Discovery team and potential of our Dolaflexin platform,” noted Anna Protopapas, President and Chief Executive Officer of Mersana.

“We are grateful to the Conference for this recognition and will continue to commit ourselves to developing novel cancer treatments to address ongoing patient needs,” she added.

Pipeline
Using the company’s Dolaflexin technology platform, Mersana has rapidly developed a burgeoning oncology pipeline that includes two compounds that are advancing towards clinical studies. XMT-1522, Mersana’s first pipeline product, defines a new class of HER2-targeted therapies.

The investigational drug is an anti-HER2 ADC that incorporates HT-19, a novel, human anti-HER2 antibody optimized for cytotoxic payload delivery.[1]  In addition HT-19 was selected to be non-competitive for HER2 binding with existing therapies – trastuzumab or pertuzumab, to allow the potential of combination therapies.

XMT-1522 is armed with about 15 auristatin molecules per antibody, making it highly potent in tumor models that express relatively low amounts of the HER2 protein. XMT-1522 has the potential to extend HER2-targeted therapy beyond the current HER2+ population into patients with lower levels of HER2 expression.

The second pipeline product, XMT-1536, is a highly potent anti-sodium-dependent phosphate transport protein 2B (anti-NaPi2b) immunoconjugate comprised of an average of 15 auristatin molecules conjugated to XMT-1535, a novel humanized anti-NaPi2b antibody. Earlier this year during the 2016 annual meeting of the American Association for Cancer Research (AACR), data were presented that demonstrated significant anti-cancer activity in non-small cell lung cancer (NSCLC) and ovarian cancer tumor models.[2]

investigational compound known as XMT-1536 may help patients with NaPi2b-expressing tumors. Preclinical data with this immunoconjugate product demonstrated significant anticancer activity in NSCLC and ovarian cancer tumor models. Based on the data presented during the annual meeting of the AACR , Mersana advanced XMT-1536 into IND-enabling studies for the treatment of patients with NaPi2b-expressing tumors.


Last Editorial Review: October 13, 2016

Featured Image: 7th World ADC, San Diego, CA Courtesy: © Sunvalley Communication, LLC. 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.

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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.

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