Mersana/Takeda Deal Adds To ADC Pipeline
This article was originally published in Scrip
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.
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
Hairy cell leukemia
Acute lymphocytic leukemia
Celldex Therapeutics/Amgen/Seattle Genetics
Breast cancer, Melanoma
Myeloma, Non-Hodgkin's lymphoma, Chronic lymphocytic leukemia
Progenics Pharmaceuticals/ Seattle Genetics
Non-Hodgkin's lymphoma, Acute B-cell lymphoma
NSCLS, Breast, Gastric, Colorectal, Liver, NSCLC, Pancreatic, Prostate, Head and neck, Renal, Ovarian, oesophageal, Bladder, Cervical, Endometrial
Ovarian, Cervical, Oesophageal, Endometrial, Bladder, Prostate, Head and neck, NSCLC
Cutaneous T-cell lymphoma, Melanoma, Acute lymphocytic leukemia
Ovarian, Fallopian tube, Endometrial, Peritoneal
B-cell lymphoma, Non-Hodgkin's lymphoma
Solid tumors, Mesothelioma
Roche/ Seattle Genetics
Ovarian, Fallopian tube
Seattle Genetics/ Takeda Pharmaceuticals
AbbVie (Abbott)/Seattle Genetics
Brain, NSCLC, Head and neck, Colorectal
Acute Myelogenous leukemia
Small cell lung cancer
Bristol-Myers Squibb Co.