XOMA Corp. (NASDAQ: XOMA) has leveraged their
extensive expertise in allosteric modulating human and humanized monoclonal
antibody development to bring a series of potent indications up through
clinical trialing that have a potentially wide range of applications in the
areas of cardiovascular, infectious, inflammatory, and metabolic disease. Chief
among these indications is Gevokizumab (XOMA 052), which is primarily under
development for Behçet’s disease uveitis (BDU), a rare immune system-related
inflammatory disease that typically manifests repeated ulceration in the
mouth/genital area and dangerous inflammation of the eye’s uvea (core pigmented
vascular structures, including the iris), as well as non-infectious uveitis
(NIU), via the company’s EYEGUARD™ clinical program.
Gevokizumab has shown an exciting ability to
actively modulate the very cellular signaling events, which actually produce
the inflammation, by binding strongly to a key pro-inflammatory cytokine. The
drug has received orphan drug designation from the FDA and European Medicines
Agency for Behçet’s disease and XOMA has been working with privately-owned
French pharmaceutical company Les Laboratoires Servier since 2011 on the
development and commercialization of gevokizumab, with eventual commercialization
rights to be divided between the two. Under the agreement, XOMA gets rights for
the U.S. and Japan, whilst Servier gets the rest of the planet, as well as
worldwide rights to any cardiovascular disease and diabetes indications.
However, XOMA has an option to reacquire cardiovascular and diabetes rights in
the U.S. and Japan via an option fee and partial reimbursement of development
expenses, giving the company the opportunity to later license these rights out
to one or more third parties.
Following pivotal Phase 2 clinical study
successes in BDU back in 2010, XOMA and Servier kicked off a global gevokizumab
Phase 3 clinical program (EYEGUARD) that actually encompasses a host of
diseases classed under the NIU designation. The company is currently
progressing superbly with their EYEGUARD Phase 3 work and is well within
striking distance of becoming an attractive commercial enterprise, having got a
major shot in the arm from Servier, which paid the first $50M of NIU
development costs and carried development through to Q3 2013. Clinical
development costs for the EYEGUARD program have been roughly equivalent between
the two companies since late 2013 and work is progressing on three fronts. The
first front is looking at treating active NIU (EYEGUARD-A), the second is the
Servier-run study to see if gevokizumab helps BDU patients who are experiencing
an exacerbation while reducing steroid dosage (EYEGUARD-B), and the third is a
study evaluating gevokizumab’s efficacy in helping physicians to reduce overall
corticosteroid usage to maintain control over the patient’s NIU (EYEGUARD-C).
XOMA’s U.S. clinical trialing in BDU
(EYEGUARD-US), which began enrollment in September 2014, is designed to
supplement previous Phase 2 efforts, as well as Servier’s EYEGUARD-B study, and
the company plans to seek a pre-BLA (Biologics License Applications) meeting
with FDA after they get their hands on the EYEGUARD-B data. The company also
announced initiation of the first of two pivotal Phase 3 trials of gevokizumab
in pyoderma gangrenosum (PG) recently. This is another major milestone for the
company’s development of gevokizumab and it represents a potential
breakthrough, as there is currently no FDA-approved therapy for conditions
under the neutrophilic dermatoses umbrella, where PG is classified. PG is a
relatively uncommon condition, but causes often severe tissue ulcers that can
develop into chronic wounds. The condition is typically associated with
systemic diseases like the IBDs (inflammatory bowel diseases) ulcerative
colitis and Crohn’s disease, among others.
While much of the market analysis to date has
been on the company’s immediate clinical-stage portfolio of indications that
are being readied for commercialization, many analysts have largely overlooked
XOMA’s robust development pipeline, where the bedrock value of the company
truly rests. XOMA has engineered a comprehensive antibody development
architecture, including their ADAPT™ (Antibody Discovery Advanced Platform
Technologies) platform, which seamlessly integrates a proprietary library of
phage displays with yeast and mammalian for rapid antibody discovery. The
company also has ingeniously innovative supplementary technologies, like a
monoclonal antibody, biological pathway modulation technology known as ModulX™,
as well as their OptimiX™ system, which is a collection of antibody engineering
technologies designed to fully optimize key biophysical properties like
affinity, immunogenicity, manufacturability, and stability.
ADAPT’s competitive advantages are abundant,
from a host of proprietary cell-based panning and screening methodologies
developed during years of antibody discovery work, to proprietary bacterial
strains. The ADAPT platform’s extremely diverse phage display antibody
libraries, with highly flexible antibody expression option capabilities, make
it one of the truly compelling reasons for investors to take a closer look at
the company. The powerful ADAPT platform allows for rapid transitioning from
phage to yeast and mammalian display, delivering accelerated sequence analysis
and hit-to-lead clone tracking that is head and shoulders above the
competition, with the aid of XOMA’s custom software bundle, including SeqAgent™
and XAbTracker™. In fact, you could put this platform in a league of its own. Coupled
with OptimiX and ModulX, the ADAPT platform offers incredibly high-speed
antibody discovery, and has the optimization and manufacturing muscle to make
the overall engine easily capable of continuing to deliver fruits for the
company moving forward, particularly as a partner in discovery and development
work on new antibodies.
XOMA has successfully earned revenue from a
variety of licensing agreements and development collaborations already thanks
to their powerful antibody development technologies, including Roche’s (OTCQX:
RHHBY) Lucentis® for wet age-related macular degeneration and UCB’s (EBR:UCB)
CIMZIA® for rheumatoid arthritis and Crohn’s disease. The company has signed 60
biopharma companies to license their breakthrough Bacterial Cell Expression
(BCE) technology alone to date and truly has one of the most compelling
antibody discovery and development frameworks in existence today at their
disposal. It is this ability to develop whole new classes of therapeutic
antibodies, with wide-ranging potential to treat a variety of human diseases,
that really makes XOMA such an attractive investment target (although the
portfolio of clinical indications is, of course, nothing to sneeze at).
The presentation back in mid-2011 for instance,
of XOMA’s discovery of two new classes of fully human monoclonal antibodies
which can activate or sensitize the receptor for insulin (in vivo), brought
about two wholly novel approaches to diabetes therapy. This work achieved a
significant milestone during December 2014 with the launch of a Phase 1 safety
and tolerability study in intravenously dosed XOMA 358 (XMetD), one of the
leading compounds from the company’s XOMA Metabolic program, known as XMet
(insulin receptor program). The company has three product candidates in all
under the XMet banner (XMetA, XMetD and XMetS) and fully intends to license
with a partner having considerable expertise in developing Type 1 and 2
diabetes compounds eventually, in order to get the most out of this particular
vector. XMetA antibodies could provide long-acting relief and reduce the
frequency of insulin injections, while XMetS antibodies reduce insulin
resistance, allowing patients to more ably use the insulin generated by their
own bodies.
XOMA’s proprietary antibody discovery and development
platform even has serious potential in the field of oncology and fibrosis, with
research into numerous candidate antibodies underway that modulate or block
Transforming Growth Factor (TGF), which is responsible for homeostatic growth
of premalignant cells. TGF beta (TGF-β) over-expression is a classic hallmark
of rapid advancement in a variety of cancers and fibroses, and XOMA may have
some serious firepower in this arena, using antibody candidates that have even
demonstrated unique immunomodulatory properties as well. XOMA currently has two
monoclonal antibody products in development under partnership with Novartis
(NYSE:NVS) for treating specific breast and prostate cancers.
XOMA has even leveraged their three decades
plus of antibody development experience to secure over $120M to date in U.S.
government contracts under the botulism-related biodefense program, with XOMA
3AB in Phase 1 under NIAID (National Institute of Allergy and Infectious
Diseases) sponsorship. Extant preclinical and IND-enabling work has already
shown XOMA 3AB to be well-tolerated, safe and effective at clearing and
neutralizing botulinum toxin Type A from the blood in animal models. Moreover,
the company’s powerful antibody development platform holds the promise to
create other antibody co-formulation therapeutics capable of cleansing the
blood of the types of botulinum toxin.
Dig deeper into XOMA Corp. by visiting their
website at www.XOMA.com
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