Allakos Announces Publication of AK006 Mechanism of Action Manuscript in Communications Biology
29 November 2022 - 11:02PM
Allakos Inc. (Nasdaq: ALLK), a clinical-stage biotechnology company
developing therapeutics which target immunomodulatory receptors
present on immune effector cells involved in allergy, inflammatory
and proliferative diseases, today announced the publication of
“Discovery of an agonistic Siglec-6 antibody that inhibits and
reduces human mast cells,” in Communications Biology. The
publication describes the generation of Siglec-6 agonist monoclonal
antibodies optimized for mast cell inhibition and their ability to
suppress mast cell activity in pre-clinical models.
Siglec-6 is an inhibitory receptor selectively expressed on mast
cells. Binding of AK006 to Siglec-6 activates the native inhibitory
function of the receptor which in turn reduces mast cell
activation. In pre-clinical studies, AK006 inhibited multiple modes
of mast cell activation, including IgE, IL-33, KIT, C5a, and
MRGPRX2, resulting in the broad suppression of inflammation. In
addition to mast cell inhibition, AK006 reduced human tissue mast
cells via antibody-dependent cellular phagocytosis (ADCP).
Publication Details
The paper describes the identification of an epitope within the
extracellular domain of Siglec-6 that allows for prolonged
residence time on the mast cell surface. This high residence time
of Siglec-6 on the surface of the mast cell contributes to the
ability of AK006 to mediate deep mast cell inhibition via receptor
agonism. Key findings of the publication include:
- Identification of a Siglec-6 antibody that confers optimal mast
cell inhibitory activity and ADCP function
- Administration of this Siglec-6 antibody prevents systemic
anaphylaxis in humanized mice with a single dose and reduces mast
cell numbers with multiple doses
- Engagement of Siglec-6 with an agonistic antibody induces
formation of immunoregulatory synapses that recruit inhibitory
signaling molecules that are required for potent mast cell
inhibition
Allakos is currently completing IND-enabling studies and expects
to begin in-human studies in the first half of 2023 in healthy
volunteers and subsequently in patients with mast cell driven
diseases.
About Allakos
Allakos is a clinical stage biotechnology company developing
therapeutics which target immunomodulatory receptors present on
immune effector cells involved in allergy, inflammatory and
proliferative diseases. Activating these immunomodulatory receptors
allows for the direct targeting of cells involved in disease
pathogenesis and, in the setting of allergy and inflammation, has
the potential to result in broad inhibition of inflammatory cells.
In proliferative diseases like cancer, blocking an inhibitory
receptor can restore the immune system’s ability to identify and
kill proliferative cells. The Company’s most advanced antibodies
are lirentelimab (AK002) and AK006. Lirentelimab selectively
targets both mast cells and eosinophils, two types of white blood
cells that are widely distributed in the body and play a central
role in the inflammatory response. Inappropriately activated mast
cells and eosinophils have been identified as key drivers in a
number of severe diseases affecting the gastrointestinal tract,
eyes, skin, lungs and other organs. Allakos is developing
lirentelimab for the treatment of atopic dermatitis, chronic
spontaneous urticaria and potentially additional indications.
Lirentelimab has received orphan drug designations for eosinophilic
gastritis (EG), eosinophilic duodenitis (EoD), and eosinophilic
esophagitis (EoE) from the U.S. Food and Drug Administration. AK006
targets Siglec-6, an inhibitory receptor expressed selectively on
mast cells. In pre-clinical research, AK006 appears to provide
deeper mast cell inhibition than lirentelimab and, in addition to
its inhibitory activity, reduce mast cell numbers. Allakos plans to
begin human clinical trials with AK006 in the first half of 2023.
AK007 targets Siglec-10, a key inhibitory myeloid checkpoint
receptor that is selectively expressed on tumor associated
macrophages (TAMs) and dendritic cells (DCs). AK007 blocks all
known ligand interaction with Siglec-10, including the “don’t eat
me” signal CD24. More recently, “don’t eat me” signals, such as
CD47 and CD24, have been identified to be overexpressed in tumors
and allow cancer cells to avoid destruction by macrophages and
other myeloid cells of the innate immune system. In pre-clinical
research, AK007 polarizes tumor-associated myeloid cells and
promotes anti-tumor immunity. Allakos is currently conducting
pre-clinical studies with AK007. For more information, please visit
the Company's website at www.allakos.com.
Forward Looking Statements
This press release contains forward-looking statements within
the meaning of the Private Securities Litigation Reform Act of 1995
as contained in Section 27A of the Securities Act of 1933, as
amended, and Section 21E of the Securities Exchange Act of 1934, as
amended. Such forward-looking statements include, but are not
limited to, Allakos’ progress, business plans and areas of focus,
the potential of AK006, and the timing of initiation of a
first-in-human study with AK006. Such statements are subject to
numerous important factors, risks and uncertainties that may cause
actual events or results to differ materially from current
expectations and beliefs, including but not limited to: Allakos’
stages of clinical drug development; Allakos’ ability to timely
initiate and complete pre-clinical studies, and initiate clinical
trials, for AK006; Allakos’ ability to obtain required regulatory
approvals for its planned clinical trials; uncertainties related to
the enrollment of patients in its clinical trials; Allakos’ ability
to demonstrate sufficient safety and efficacy of its product
candidates in its clinical trials; uncertainties related to the
success of clinical trials, regardless of the outcomes of
pre-clinical testing or early-stage trials; Allakos’ ability to
obtain regulatory approvals to market its product candidates;
market acceptance of Allakos’ product candidates; uncertainties
related to the projections of the size of patient populations
suffering from the diseases Allakos is targeting; Allakos’ ability
to advance additional product candidates beyond lirentelimab;
Allakos’ ability to obtain additional capital to finance its
operations; general economic and market conditions; and other
risks. Information regarding the foregoing and additional risks may
be found in the section entitled “Risk Factors” set forth in
Allakos’ most recent Annual Report on Form 10-K filed with the SEC
on March 1, 2022, Allakos’ Quarterly Report on Form 10-Q filed with
the SEC on November 7, 2022, and future reports to be filed with
the SEC. These documents contain and identify important factors
that could cause the actual results for Allakos to differ
materially from those contained in Allakos’ forward-looking
statements. Any forward-looking statements contained in this press
release speak only as of the date hereof, and Allakos specifically
disclaims any obligation to update any forward-looking statement,
except as required by law. These forward-looking statements should
not be relied upon as representing Allakos’ views as of any date
subsequent to the date of this press release.
Investor Contact:Adam Tomasi, President and COOAlex Schwartz, VP
Strategic Finance and Investor Relationsir@allakos.com
Media Contact:Denise Powelldenise@redhousecomms.com
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