Momenta Pharmaceuticals, Inc. (MNTA)

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Biocentury Innovations article - January 17, 2017

THREE TIMES A CHARM [Excerpts]

With this month’s deal between Momenta Pharmaceuticals Inc.
(NASDAQ:MNTA) and CSL Ltd. (ASX:CSL), the partners are
hoping to take IVIG therapy for autoimmune diseases to the
next level by homing in on the cornerstone of how the therapy
works — Fc? receptor (FCGR) inhibition. The goal is to define
the optimal number and composition of Fc domains required
to recapitulate the breadth of IVIG activity, but produce greater
potency.

Momenta SVP of Research Anthony Manning told BioCentury
that M230 represents a significant advance on intravenous
immunoglobin (IVIG), which is made by isolating antibodies
from the blood of healthy volunteers, but has poorly defined
compositions and complex effects in patients.

“I think many of the analysts thought ‘oh you’re just going to
replace IVIG with a recombinant product.’ But, we’re going to
take one of the mechanisms of action of IVIG and make a much
more potent and effective molecule,” said Manning. He added
that the companies plan to test the compound in patients who
don’t respond to IVIG.

In mouse models of rheumatoid arthritis, immune
thrombocytopenic purpura (ITP) and the skin blistering disease
epidermolysis bullosa acquisita, the team showed the Fc trimer
provided significant therapeutic benefit compared with vehicle
and was 10- to 40-fold more potent than an IVIG therapy (see
Distillery, Autoimmune Disease).

Because other immunosuppressive therapies for autoimmunity
increase risk of infection, the Momenta team administered
the trimer to rodents and monkeys housed under non-sterile
conditions. After three months of dosing, the company found
no infections in any of the animals, similar to vehicle-treated
animals. “We have gone to the maximum feasible dose possible,”
said Manning. “We were up in the hundreds of milligrams per
kilo. I can tell you over the three months we had complete saturated every Fc? receptor for twenty four hours every day and to date, the toxicology profile is very, very benign.”

CSL and Momenta plan to initiate a clinical trial for M230 this
year.

http://www.momentapharma.com/012617IN_TIB_ThreeTimesACharm.pdf