CoGenesys is seeking to outlicense a substantial intellectual
property estate as well as lead molecules (antibodies and proteins) for 7
well-validated opportunities in both inflammation and oncology. These product
opportunities are based on biologic mechanisms that are well validated in the
literature. Each product is accompanied by patents and patent applications held
by CoGenesys. Many of these targets offer the opportunity for development
across multiple indications.
HVEM-Fc for inflammation - One drug targeting both T and B cell mediated inflammation
HVEM-Fc inhibits T cell costimulation in a manner similar to
CTLA4-Fc (Orencia® (abatacept), sold by BMS).
HVEM-Fc has the potential for superior efficacy and therapeutic utility
for a broader class of diseases because, acting through BTLA, HVEM-Fc inhibits
both B and T cell proliferation. There are now numerous products in clinical
development for autoimmune disease separately targeting the B cell
and the T cell, illustrating the unique
potential of HVEM-Fc. HVEM-Fc has a
third, important inhibitory effect on a key pro-inflammatory pathway: it
inhibits the role of another TNF family member in immune stimulation by
preventing LIGHT/LTβR-mediated inflammation. LIGHT and
antibodies to LIGHT are also available for licensing from CoGenesys (see
below). Our data shows that HVEM-Fc inhibits T-cell costimulation, B-Cell
proliferation and provides therapeutic benefit in murine models of disease. A
lead Fc fusion protein and intellectual property on HVEM are available as part
of a licensing package.
HVEM References
Anti-LIGHT for hepatitis and inflammatory bowel diseases -
Ligand of HVEM, pro-inflammatory cytokine, target for IBD and hepatitis
LIGHT is a potent pro-inflammatory cytokine in theTNF ligand
family. By preventing LIGHT/LTβR-mediated
inflammation, LIGHT antagonism with HVEM-Fc or an antibody to LIGHT has been
shown to provide therapeutic benefit in preclinical modes of autoimmune
disease. LIGHT and antibodies to LIGHT are available for licensing from
CoGenesys. LIGHT plays an especially important and therapeutically accessible
role in gastrointestinal and liver inflammation and thus the LIGHT mAb is a
unique opportunity for a new treatment for hepatitis and IBD. A lead monoclonal
antibody and intellectual property on LIGHT are available as part of a
licensing package.
LIGHT References
Anti-CD200R for autoimmune disease and asthma - Strongly validated target for immune
suppression in RA, transplant and other autoimmune diseases
Monoclonal antibodies against CD200R and soluble forms of CD200
(the ligand for CD200R), provide therapeutic reductions in inflammation
associated with RA and substantial reductions in transplant rejection in mice
[1-5]. Engagement of CD200R by its ligand or by agonist antibodies inhibits
mast cell degranulation [6-10], down regulates the macrophage lineage [5], and
reduces TH1 responses in vivo [2, 8, 11-14]. Abundant data support the utility
of CD200R antibodies in development of a novel therapeutic for the treatment of
autoimmune diseases, transplant rejection, and mast-cell dependent inflammatory
conditions like asthma and allergy. A lead monoclonal antibody and intellectual
property on CD200R are available as part of a licensing package.
CD200R References
Anti-CXCL16 for autoimmune disease -
Target to treat inflammation in numerous tissues including, liver, lung, CNS, joint synovium and vasculature
The therapeutic rationale for development of an antibody to CXCL16
has recently been validated in a number of murine models: Antibody-mediated
blockade of this chemokine provides therapeutic benefit in acute EAE, a murine
model immunological liver injury, and in collagen-induced arthritis. CXCL16 is
an interferon-gamma-regulated chemokine elevated in atherosclerotic plaques
[1-3] and during inflammatory states in the liver [4-6], CNS [7], lung [8, 9]
and joint synovium of patients with inflammatory disease [10, 11]. The severity
of coronary artery stenosis was recently associated with a polymorphism in the
CXCL16 gene [12] and it may play a role in inflammatory valvular heart disease
[13]. Also known as the scavenger receptor that binds phosphatidylserine and
oxidized lipoprotein (SR-PSOX), CXCL16 is a membrane-bound and soluble chemokine
expressed on macrophages and dendritic cells, while its receptor (CXCR6) is
expressed on T and NK T cells. The interaction between SR-PSOX/CXCL16 and CXCR6
plays an important role in enhancing T cell responses by mature DCs in lymphoid
tissues and in augmenting memory T cell responses by macrophages in peripheral
inflamed tissues [14]. Given the abundant recent evidence that CXCL16 plays an
important and therapeutically accessible role in numerous inflammatory states,
it is an excellent candidate for development of a novel biologic that could
complement the growing list of successful biologics in the large and growing
anti-inflammatory market. A lead monoclonal antibody and intellectual property
on CXCL16 are available as part of a licensing package.
CXCL16 References
Anti-CXCR3 for autoimmune disease -
Key target in T cell mediated inflammation, for treatment of autoimmune disease
CXCR3 plays a key role in T cell activation, allograft
destruction, and recruitment to sites of inflammation in diseases like Crohn’s,
MS, and RA. CoGenesys has developed a humanized CXCR3 antibody that blocks all
three ligands of this receptor. As a T cell targeting therapy, anti-CXCR3 is
expected to have anti-inflammatory properties in a broad class of autoimmune
diseases. Because CXCR3 antagonism prevents effector T cell recruitment, but
not naive T cell response, the antibody could reduce the tissue damage,
swelling and pain associated with chronic inflammation without having the
global immune-suppressive actions of conventional steroid treatments and
anti-TNFs. Substantial validation exists for CXCR3 antagonism providing benefit
in transplant rejection and other inflammatory conditions and provides strong
support for clinical development of an antibody targeting CXCR3. A high-affinity
humanized monoclonal antibody and intellectual property on CXCR3 are available
as part of a licensing package.
CXCR3 References
Anti-TL1A for inflammatory bowel diseases -
Target for treatment of inflammatory bowel disease
TL1A gene polymorphisms are strongly associated with high risk of
Crohn’s disease in Japanese (P<10-10) and European IBD populations
(p<0.02) [1]. TL1A is a pro-inflammatory cytokine and a member of the TNF
family [2]. This protein exists in both membrane-bound and soluble forms and it
is highly expressed in the inflamed bowel. TL1A is the only known ligand for
death-domain receptor DR3 [2], which is primarily expressed on activated
lymphocytes [2, 3]. Binding of TL1A to DR3 triggers proliferative activation
signals [2, 4] specifically in memory T cells, but not naive T cells and TL1A
potently induces secretion of IFN-g by human T cells [2, 5-7].
Moreover, both TL1A and DR3 are highy
expressed in inflammatory bowel disease (IBD), particularly Crohn’s disease
(CD) [6-13]. TL1A is also highly expressed in the joints of RA patients, where
it may play a role in the T cell mediated inflammation (unpublished) and there
is evidence that TL1A is up-regulated in response to toll receptor activation
in the gut, where it likely participates in the initiation of IBD flares
(unpublished). A lead monoclonal antibody and intellectual property on TL1A are
available as part of a licensing package.
TL1A References
Anti-PD-L2 for oncology, asthma and vaccine enhancement -
Stimulate antigen presentation, shift immune response to TH1, enhance vaccine efficacy
A naturally occurring human antibody potentiates dendritic cell
function on cross-linking PD-L2 (aka B7-DC), supporting robust T cell responses
to tumors [1-3]. This same antibody significantly inhibits allergic airway
inflammation in a murine model of asthma [4-6]. The mechanism of action of this
PD-L2 antibody involves multiple pathways initiated through PD-L2 expressed on
dendritic cells. The outcome of the action of the PD-L2 antibody is augmented
antigen presentation, enhanced NK T cell proliferation, antibody formation in
response to antigen, and a shift from TH2 to TH1 phenotype in T cell
populations in vivo. In different settings, these actions lead to reductions in
allergic response and to augmentation of a natural anti-tumor response. Enhanced
dendritic cell-mediated presentation of antigens by this antibody could also be
exploited to enhance the potency of vaccines. We have generated a panel of
fully human PD-L2 antibodies suitable for development as human therapeutics. A
lead monoclonal antibody and intellectual property on PD-L2 are available as
part of a licensing package.
PD-L2 References
References for Licensing Opportunities
