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Mersana/Takeda Deal Adds To ADC Pipeline

This article was originally published in Scrip

Executive Summary

Mersana Therapeutics is getting a vote of confidence from long-time partner Takeda Pharmaceuticals as the two companies expand their collaboration in antibody-drug conjugates and plan to move a molecule into the clinic.

The biotech announced Feb. 3 that Takeda will pay $40m upfront for rights to XMT-1522, an antibody-drug conjugate (ADC) that targets HER2. Mersana will receive another $20m once an IND is accepted by FDA, which is expected in mid-2016. Mersana will be responsible for preclinical and Phase I work, while the pair intend to work together on development beyond that point. Mersana retains US and Canadian rights to the drug, with Takeda taking responsibility for rest-of-world commercialization.

Beyond XMT-1522, the two companies will develop drugs using Mersana's Fleximer ADC platform against targets that Takeda selects. The biotech will have the option to co-development and co-commercialize one molecule of its choice that comes out of the collaboration. All told, Mersana is eligible for $750m in milestone payments.

XMT-1522 will be tested in four groups of patients – those with breast, gastric and non-small cell lung cancers, as well as patients that have shown resistance to currently HER2-targeted therapies. The company wants to concentrate on low-expressing HER2 patients that do not respond well to many of the currently available treatments.

This will be the first molecule that the pair move into the clinic, but far from its first partnership. Takeda and Mersana initially teamed up in April 2014. The original deal allowed Takeda to use the Fleximer platform for a small number of targets. That partnership was later expanded in January 2015 and again now. Mersana CEO Anna Protopapas told Scrip that Mersana could gain almost $1bn from Takeda through all three iterations of the deal and another $1bn in other partnerships.

Protopapas has seen both sides of this deal and has shown her true faith in the platform; the CEO joined the company in March 2015 from Takeda's oncology unit, formerly known as Millenium Pharmaceuticals.

"Three partnerships in two years is a testament to the fact that we are making real progress," said Protopapas, who noted that the lead program, XMT-1522, "is very robust." She pointed out that Mersana's ADCs can attach 15 drugs to the antibody, instead of the typical four seen in other ADCs.

ADCs have been evolving over the last several years and are becoming of increased interest to many companies. ADCs are made up of a cytotoxic payload attached with a linker to an antibody that is delivered directly to cancer cells, allowing for less damage to surrounding healthy cells.

Only three ADCs have ever reached the market – Pfizer's Mylotarg (gemtuzumab ozogamicin), which was later withdrawn; Roche's Kadcyla (trastuzumab), an ADC of the blockbuster Herceptin; and Takeda's own Adcetris (brentuximab), developed by ImmunoGen.

ADC Resurgence

After some struggling, the compounds are making a resurgence – the pipeline for ADCs has more than doubled over the last five years. According to Citeline's Pharmaprojects, there are currently two ADCs in Phase III and another 21 in Phase II, as well as 30 more compounds in Phase I. Both the Phase III drugs were in that phase of development when Mersana and Takeda signed their initial deal in April 2014, but the mid-stage pipeline has ballooned – there were only 15 compounds in Phase II at the time. Seattle Genetics and ImmunoGen are leading the development of ADCs, with 22 and 10, respectively, active compounds in development.

Late- and Mid-stage ADC Pipeline





Originating and Licensing Companies


Cancer Indication


Phase III


moxetumomab pasudotox


AstraZeneca/ Genencor


Hairy cell leukemia


Phase III


inotuzumab ozogamicin


Pfizer/ UCB


Acute lymphocytic leukemia


Phase II


glembatumumab vedotin


Celldex Therapeutics/Amgen/Seattle Genetics


Breast cancer, Melanoma


Phase II






Myeloma, Non-Hodgkin's lymphoma, Chronic lymphocytic leukemia


Phase II




Helix BioPharma




Phase II




Progenics Pharmaceuticals/ Seattle Genetics




Phase II


coltuximab ravtansine




Non-Hodgkin's lymphoma, Acute B-cell lymphoma


Phase II


indatuximab ravtansine






Phase II




Seattle Genetics


Non-Hodgkin's lymphoma


Phase II


isactuzumab govitecan




NSCLS, Breast, Gastric, Colorectal, Liver, NSCLC, Pancreatic, Prostate, Head and neck, Renal, Ovarian, oesophageal, Bladder, Cervical, Endometrial


Phase II


labetuzumab govitecan






Phase II




GenMab/Seattle Genetics


Ovarian, Cervical, Oesophageal, Endometrial, Bladder, Prostate, Head and neck, NSCLC


Phase II






Cutaneous T-cell lymphoma, Melanoma, Acute lymphocytic leukemia


Phase II


mirvetuximab soravtansine




Ovarian, Fallopian tube, Endometrial, Peritoneal


Phase II


polatuzumab vedotin


Roche/Seattle Genetics


B-cell lymphoma, Non-Hodgkin's lymphoma


Phase II


anetumab ravtansine


Bayer/ MorphoSys/ImmunoGen


Solid tumors, Mesothelioma


Phase II


lifastuzumab vedotin


Roche/ Seattle Genetics


Ovarian, Fallopian tube


Phase II




Seattle Genetics/ Takeda Pharmaceuticals


Oesophageal, Pancreatic


Phase II


depatuxizumab mafodotin


AbbVie (Abbott)/Seattle Genetics


Brain, NSCLC, Head and neck, Colorectal


Phase II


vadastuximab talirine


Seattle Genetics


Acute Myelogenous leukemia


Phase II


rovalpituzumab tesirine


Stem CentRx


Small cell lung cancer


Phase II




Bristol-Myers Squibb Co.


Solid tumors


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