Angiochem,
a clinical stage biotechnology company creating and developing drugs
that cross the blood-brain barrier, today announced the publication in Molecular
Cancer Therapeutics demonstrating that ANG4043, a peptide-monoclonal
antibody (mAb) conjugate, entered the brain at therapeutic
concentrations, resulting in significantly prolonged survival in mice.
The antibody is directed against HER2, which is the protein targeted by
Herceptin®. Because the mAb is conjugated to Angiopep-2, it is
recognized by the LRP1 receptor and takes advantage of a
receptor-mediated transcytosis mechanism to cross the BBB. This
proprietary technology has been clinically validated with ANG1005, a
peptide-paclitaxel conjugate currently in Phase II studies. The data
published today shows that Angiochem’s technology to cross the BBB is
applicable to biologics such as mAbs.
In the publication entitled “ANG4043, a Novel Brain-penetrant
Peptide-mAb Conjugate, is Efficacious against HER2-positive Intracranial
Tumors in Mice,” Angiochem researchers show that ANG4043 binds LRP1
receptors while retaining the pharmacological properties of the native
anti-HER2 mAb, including high affinity HER2 binding and
anti-proliferative activity in HER2-expressing cells. In vivo, ANG4043
achieves therapeutic brain concentrations in healthy mice and in mice
bearing intracranial HER2+ tumors, which are targeted by ANG4043. In
this HER2+ intracranial tumor model, treatment with ANG4043 (15 mg/kg
IV, twice-weekly) increased median survival time by 78% (80 days
compared to 45 days for control).
“To the best of our knowledge, the data reported in this publication
represent the first known peptide-monoclonal antibody conjugate for
oncology that has been shown to cross the BBB using a
clinically-validated technology. For biologics and more specifically for
mAbs, brain penetration is the major obstacle for the treatment of CNS
diseases,” said Jean Paul Castaigne, M.D., President and CEO of
Angiochem. “These data build upon previously reported Phase 2 clinical
data with ANG1005, our peptide-paclitaxel drug conjugate, demonstrating
indication of efficacy in primary and secondary brain tumors.”
Jean Lachowicz, Ph.D., CSO at Angiochem, continued, “LRP-1
receptor-mediated transcytosis, can be leveraged to create brain
penetrant mAbs, as demonstrated in the study published today, as well as
Angiopep antibody-drug conjugates, which have been successfully
generated by Angiochem. While our current data has focused on
demonstrating the potential of Angiochem’s technology in oncology, its
applicability extends beyond oncology to include neurodegenerative
diseases as well.”
About ANG4043
ANG4043 was created by conjugating the Angiopep-2 to an anti-HER2 mAb to
bring an effective anticancer therapy to treat HER2+ brain metastases
from breast cancer. In a series of in vivo experiments, ANG4043 has
demonstrated that it reaches the brain, targets HER2+ tumors, induces
intracranial tumor shrinkage, and significantly increases survival in
mice that have been intracranially implanted with HER2+ tumor cells.
Overall study results of ANG4043 further validate the potential of the
applicability of Angiochem technology to create brain-penetrant mAbs.
About
Angiochem
Angiochem is a clinical-stage biotechnology company discovering and
developing new breakthrough peptide drug conjugates that leverage the
LRP-1 mediated pathway to cross the BBB for treating neurological
diseases. These new compounds have the potential to address significant
medical needs, many of which are insurmountable due to the fundamental
physiological challenge posed by the BBB. Angiochem is developing a
focused product pipeline, including small molecules and biologics, for
the potential treatment of brain malignancies and other CNS indications.
Angiochem maintains headquarters in Montreal, Canada. For additional
information about the Company, please visit http://www.angiochem.com.
Copyright Business Wire 2014