Mersana/Takeda Deal Adds To ADC Pipeline

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

Phase

 

Drug

 

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

 

milatuzumab-doxorubicin

 

Immunomedics

 

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

 

Phase II

 

L-DOS-47

 

Helix BioPharma

 

NSCLC

 

Phase II

 

PSMA ADC

 

Progenics Pharmaceuticals/ Seattle Genetics

 

Prostate

 

Phase II

 

coltuximab ravtansine

 

ImmunoGen/Sanofi

 

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

 

Phase II

 

indatuximab ravtansine

 

Biotest/ImmunoGen

 

Myeloma

 

Phase II

 

denintuzumab

 

Seattle Genetics

 

Non-Hodgkin's lymphoma

 

Phase II

 

isactuzumab govitecan

 

Immunomedics

 

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

 

Phase II

 

labetuzumab govitecan

 

Immunomedics

 

Colorectal

 

Phase II

 

HuMax-TF

 

GenMab/Seattle Genetics

 

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

 

Phase II

 

Resimmune

 

Angimmune

 

Cutaneous T-cell lymphoma, Melanoma, Acute lymphocytic leukemia

 

Phase II

 

mirvetuximab soravtansine

 

ImmunoGen

 

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

 

TAK-264

 

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

 

BMS-986148

 

Bristol-Myers Squibb Co.

 

Solid tumors