cCAM Biotherapeutics, a biopharmaceutical company focused on the
discovery and development of novel cancer immunotherapies, announced
today that it has received approval form the US Food and Drug
Administration to commence a Phase 1 trial for CM-24, a first-in-class
immunomodulatory monoclonal antibody (mAb) for the treatment of various
types of cancers. The study is expected to commence during the first
quarter of 2015.
CM-24 is directed against CEACAM1, a novel immune checkpoint protein
that is expressed on activated effector lymphocytes and a variety of
cancer cells. CEACAM1 belongs to the Human CEA protein family, and
preclinical data show that inhibition of CEACAM1-CEACAM1 homophilic
interactions by CM-24 leads to enhanced activation of tumor specific
immune cells.
The Phase 1 trial is a first-in-human, open-label, multicenter, dose
escalation study assessing the effect of the CM-24 mAb in cancer
patients with selected advanced or recurrent malignancies, including
melanoma, non-small cell lung adenocarcinoma (NSCLC) and bladder,
gastric, colorectal or ovarian cancer. Primary objectives of the study
are to assess the safety and tolerability of escalating multiple doses
of CM-24 and to determine the recommended dose for Phase 2 trials with
CM-24. Secondary objectives include characterization of the
pharmacokinetic profile and immunogenicity of CM-24, and the evaluation
of the preliminary efficacy of the drug on the basis of objective tumor
response and duration of response in subjects treated with CM-24. The
trial will be conducted at four sites including Yale and UCLA, and will
be composed of a dose escalation stage and an expansion stage. The
expansion stage will focus on subjects with cutaneous melanoma or
additional malignancies that responded to treatment in the first stage
of the study.
Pini Orbach, Ph.D., Chairman of the Board, cCAM Biotherapeutics, stated:
“Antibodies blocking immune checkpoints are emerging as a breakthrough
treatment that can, in some cases, lead to a cure even in advanced stage
cancer. Unfortunately, a large proportion of patients do not respond to
these drugs. Currently approved immune checkpoint inhibitors are based
on protein targets from the B7-CD28 family, and therefore novel immune
checkpoint targets from different protein families may increase the
response rate to treatment. cCAM is developing a first-in-class cancer
immunotherapy that is directed against a novel immune checkpoint from
the CEA protein family using a different mechanism of action than the
current immune checkpoint inhibitors on the market. We therefore hope
that our drug will increase the percentage of cancer patients responding
to treatment. This is a very exciting era in oncology, and we look
forward to launching the first-in-human clinical trial with CM-24.”
Professor Antoni Ribas, M.D., Ph.D., Department of Medicine,
Hematology/Oncology at the Jonsson Comprehensive Cancer Center, UCLA,
commented, “We are impressed by the preclinical data to date, and are
excited to take part in this trial, assessing the safety and
tolerability of a new, first-in-class immune checkpoint inhibitor.
Unlike current immune checkpoints isolated to date, CEACAM1 acts both as
the receptor and the ligand. CEACAM1 on a tumor cell binds to another
CEACAM1 molecule on an immune cell in order to inhibit an immune attack
on the tumor. Therefore, it is possible that the CM-24 antibodies
blocking the activity of CEACAM1 will have a strong effect in inhibiting
this particular immune-modulating pathway.”
Tehila Ben-Moshe, Ph.D., VP R&D, cCAM Biotherapeutics, noted,
“Preclinical data demonstrate synergistic activity of various immune
checkpoint blockers, findings which encourage us to study the potential
synergy of CM-24 with other existing immune checkpoint blockers. We thus
have high hopes that patients that do not respond to current immune
checkpoint blockers could be treated with CM-24, as a standalone or
combination therapy.”
About CEACAM1 and CM-24
CEACAM1 is a novel immune checkpoint protein that belongs to the Human
CEA (Carcino-Embryonic Antigen) protein family and is a target for
cancer immunotherapy. CEACAM1 is widely expressed on lymphocytes within
the tumor, and is also up-regulated on various cancer types including
melanoma, bladder, pancreas, colon, gastric and non-small cell lung
cancers. Furthermore, its expression correlates with poor prognosis,
suggesting that tumor cells utilize CEACAM1 to evade the immune system.
Research shows that CEACAM1-CEACAM1 interactions have an inhibitory
effect on activated lymphocytes, and that prevention of these
CEACAM1-CEACAM1 interactions enables enhanced killing of tumor cells by
T and NK immune cells.
CM-24 is a first-in-class humanized anti-CEACAM1 antibody that inhibits
the immunosuppressive effect of CEACAM1, leading to an enhanced immune
response of T and NK cells against cancer cells. Preclinical trials show
that CM-24 enhances the cytotoxic activity of tumor-infiltrating
lymphocytes (TILs) against various CEACAM1-positive tumor cell lines.
CM-24 is being developed for multiple oncological indications according
to the expression pattern of its target protein, and also has the
potential to synergize with other immune checkpoint blockers.
About cCAM Biotherapeutics
Founded in 2010, cCAM is a biopharmaceutical company focused on the
discovery and development of novel immunotherapies to treat cancer. Its
lead product, CM-24, is a Phase 1 ready, first-in-class humanized anti
CEACAM1 monoclonal antibody. CM-24 was discovered by Dr. Gal Markel,
Head of Research, Ella Institute of Melanoma, at Sheba Academic Medical
Center Hospital. Investors in the Company include Arkin Holdings,
Orbimed and Pontifax. For more information, please visit http://ccam-bio.com/.
Copyright Business Wire 2015