Our industry is highly competitive and subject to rapid and significant
technological change. Our potential competitors include large pharmaceutical
and biotechnology companies, specialty pharmaceutical and generic drug
companies, academic institutions, government agencies and research
institutions. We believe that the key competitive factors that will affect
the development and commercial success of CEM-101, Taksta and any other
product candidates that we develop are efficacy, safety and tolerability
profile, convenience in dosing, price and reimbursement. Many of our potential
competitors, including many of the organizations named below, have
substantially greater financial, technical and human resources than we do and
significantly more experience in the discovery, development and regulatory
approvals of products, and the commercialization of those products.
Accordingly, our competitors may be more successful than we may be in
obtaining FDA approval for drugs and achieving widespread market acceptance.
Our competitors’ drugs may be more effective, or more effectively marketed
and sold, than any drug we may commercialize and may render CEM-101, Taksta
or any other product candidates that we develop obsolete or non-competitive
before we can recover the expenses of developing and commercializing any
product candidates. We anticipate that we will face intense and increasing
competition as new drugs enter the market, as advanced technologies become
available and as generic forms of currently branded drugs become available.
Finally, the development of new treatment methods for the diseases we are
targeting could render our drugs non-competitive or obsolete.
We anticipate that, if approved, CEM-101 will compete with other antibiotics
that demonstrate CABP activity. These include azithromycin (sold under the
brand names Zithromax and Z-PAK by Pfizer Inc. and available as a generic),
clarithromycin (sold under the brand name Biaxin by Abbott Laboratories and
available as a generic), moxifloxacin (sold under the brand name Avelox by
Bayer AG), levofloxacin (sold under the brand name Levaquin by Johnson &
Johnson and available as a generic), linezolid (sold under the brand name
Zyvox by Pfizer Inc.), ceftriaxone (sold under the brand name Rocephin by F.
Hoffman-La Roche Ltd and available as a generic) and ceftaroline (sold under
the brand name Teflaro by Forest Laboratories, Inc.). We also are aware of
various drugs under development for the treatment of CABP, including BC-3781
(under development by Nabriva Therapeutics AG), delafloxacin (under
development by Rib-X Pharmaceuticals, Inc.), and omadacycline/PTK-796 (under
development by Paratek Pharmaceuticals, Inc.).
We anticipate that, if approved, Taksta will compete with other antibiotics
that demonstrate MRSA activity. These include vancomycin, linezolid (sold
under the brand name Zyvox by Pfizer Inc.), daptomycin (sold under the brand
name Cubicin by Cubist Pharmaceuticals, Inc.), quinupristin/dalfopristin
(sold under the brand name Synercid by Pfizer, Inc.), tigecycline (sold under
the brand name Tygacil by Pfizer Inc.), and ceftaroline (sold under the brand
name Teflaro by Forest Laboratories, Inc.). In addition, an NDA has recently
been approved for telavancin (to be sold as Vibativ by Theravance, Inc. and
Astellas Pharma, Inc.). Further, we expect that product candidates currently
in Phase 3 development, or that could enter Phase 3 development in the near
future, may represent significant competition if approved. These include
ceftobiprole (under development by Basilea Pharmaceutica AG and approved in
Canada and Switzerland), omadacycline/PTK-796 (under development by Paratek
Pharmaceuticals, Inc.), NXL-103 (under development by AstraZeneca PLC),
radezolid (under development by Rib-X Pharmaceuticals, Inc.), tedizolid
(under development by Trius Therapeutics, Inc.), delafloxacin (under
development by Rib-X Pharmaceuticals, Inc.), dalbavancin (under development
by Durata Therapeutics, Inc.) and oritavancin (under development by The
Medicines Company).
developing in both oral and intravenous, or IV, formulations initially for the
treatment of community-acquired bacterial pneumonia, or CABP, which is one of
the most serious infections of the respiratory tract. We recently completed a
successful Phase 2 clinical trial in which the oral formulation of CEM-101
demonstrated comparable efficacy to the current standard of care, levofloxacin
(commonly marketed as Levaquin TM ), with a favorable safety and tolerability
profile. We expect to initiate a pivotal Phase 3 trial for oral CEM-101 in
2012, which will be designed to serve as the basis for our planned new drug
application, or NDA. Our second program is Taksta, which we are developing in
the U.S. as an oral treatment for bacterial infections caused by Staphylococcus
aureus , or S. aureus , including methicillin-resistant S. aureus, or MRSA,
such as prosthetic joint infections and acute bacterial skin and skin structure
infections, or ABSSSI. Taksta has successfully completed a Phase 2 clinical
trial in patients with ABSSSI, demonstrating a favorable safety and
tolerability profile and comparable efficacy to linezolid (sold under the brand
name Zyvox®), the only oral antibiotic for treatment of MRSA approved by the
U.S. Food and Drug Administration, or FDA. In 2012, we expect to initiate a
Phase 2 trial with Taksta in patients with prosthetic joint infections, which
often are caused by MRSA. We have global rights (other than in certain
Southeast Asian countries) to CEM-101 and are developing Taksta for the U.S.
market.
According to Datamonitor, $19.6 billion was spent on antibiotics in 2009 in the
U.S., Japan, and the five major European markets (the U.K., Germany, France,
Italy and Spain) of which $10.2 billion was spent in the U.S. There are
numerous classes of antibiotics, each having a different mechanism of action
and resulting spectrum of activity. According to IMS Health, macrolides, the
class of antibiotics to which CEM-101 belongs, generated global sales of $4.8
billion in 2009. Antibiotics for MRSA, which is the target market for Taksta,
generated U.S. sales of $1.8 billion in 2010, according to IMS Health. Despite
the many antibiotics available and the size of the market for antibiotics, we
believe that there continues to be a need for new antibiotics for several
reasons. First, the effectiveness of many antibiotics has declined worldwide
due to bacterial resistance to the currently available antibiotics. The World
Health Organization stated in 2010 that antibiotic resistance is one of the
three greatest threats to human health, and the Centers for Disease Control and
Prevention estimates that more than 70% of U.S. hospital infections are
resistant to at least one of the antibiotics most commonly used to treat them.
Second, many existing antibiotics have known side effects that limit their use.
Third, some antibiotics do not adequately fight all of the types of bacteria
that could be involved in a particular disease. Finally, many of the existing
antibiotics used to treat serious infections are difficult or inconvenient to
administer, often requiring IV treatment in the hospital. The clinical data we
have generated suggest that CEM-101 and Taksta address each of these
challenges. As a result, we believe CEM-101 and Taksta have the potential to be
important products in the antibiotics market.
CEM-101 (Solithromycin): A Novel Oral and IV Macrolide for CABP
CEM-101 is a novel next generation macrolide that we are developing in oral and
IV formulations for respiratory tract infections, including CABP, which is one
of the most serious infectious diseases of the respiratory tract. Historically,
macrolides, such as azithromycin (commonly marketed as Zithromax® and Z-PAK
®), have been among the most regularly prescribed drugs for respiratory tract
infections. According to IMS Health, 52 million prescriptions were written for
azithromycin in the U.S. in 2010. Prescription data from IMS Health and AMR
Research suggest that 67% of azithromycin prescriptions filled outside the
hospital and over 84% of azithromycin prescriptions filled inside the hospital,
are for respiratory tract infections. However, the effectiveness of
azithromycin and earlier generation macrolides has declined due to increased
incidence of bacterial resistance. It is estimated that in the U.S., 30% of
pneumococci, the primary pathogen involved in respiratory tract infections, are
resistant to azithromycin and other macrolides. Our clinical and pre-clinical
data demonstrate that CEM-101 addresses the same pathogens as earlier
generation macrolides with activity against resistant strains, while generally
being more potent against these pathogens and having a lower incidence of
resistance development. We believe there is a significant market opportunity
for a new macrolide that is effective against resistant bacteria, retains the
traditional safety and anti-inflammatory properties of macrolides and is
available in oral and IV formulations. If approved by the FDA, CEM-101 would be
the first macrolide approved with both IV and oral formulations since
azithromycin was approved 20 years ago.
Our Phase 1 and Phase 2 clinical trials and pre-clinical studies to date have
shown that CEM-101 has the following attributes:
• A favorable safety and tolerability profile : CEM-101 has been tested in
over 220 subjects in our Phase 1 and 2 clinical trials and has
demonstrated favorable safety and tolerability. In our recent Phase 2
trial, patients treated with CEM-101 had fewer treatment emergent
adverse events than patients treated with levofloxacin, a
fluoroquinolone which is the current standard of care.
• Comparable efficacy to the current standard of care : In a recently
completed Phase 2 trial in 132 CABP patients comparing the oral
formulation of CEM-101 to levofloxacin, CEM-101 successfully
demonstrated efficacy comparable to levofloxacin.
• Potent activity against a broad range of bacteria with excellent tissue
distribution and intracellular activity: In pre-clinical studies, CEM-
101 was shown to be generally eight to 16 times more potent against
respiratory tract bacteria in vitro than azithromycin and demonstrated
activity against bacterial strains that have become resistant to older
generations of macrolides and other classes of antibiotics. As a result
of its potency and spectrum of activity, we believe that CEM-101 could
eventually be used as a monotherapy for the treatment of CABP.
• Lower incidence of resistance development: CEM-101 has a unique
structure that binds to bacterial ribosomes in three sites while earlier
generation macrolides only have one or two binding sites. Therefore,
bacteria must mutate at three sites on the ribosome to become resistant
to CEM-101. To date, we have seen no resistance to CEM-101 in our
clinical trials, and the incidence of resistance was rare in our pre-
clinical studies.
• Potential for IV, oral and suspension formulations: We are developing
both oral and IV formulations to allow patients with severe CABP to be
treated in both hospital and out-patient settings. Providing both the IV
and oral formulations will enable physicians to initiate treatment of
patients in a hospital setting with an IV formulation and then switch
them to an oral formulation of the same medication to complete the
course of treatment on an out-patient basis, known as IV-to-oral
step-down therapy. We believe this would be more convenient and cost-
effective for patients and provide pharmacoeconomic advantages to health
care systems. We intend to develop a suspension formulation for treating
bacterial infections in the pediatric population.
• Anti-inflammatory qualities to help patients feel better earlier during
treatment: In addition to their antibacterial effects, macrolides also
have anti-inflammatory properties which help patients feel better
earlier. Our pre-clinical data suggest that CEM-101 could have
significantly greater anti-inflammatory properties than azithromycin and
clarithromycin, the market-leading FDA-approved macrolides.
We are currently planning our pivotal trial program, which we believe will
require three Phase 3 trials, including one trial with oral CEM-101 and two
trials with IV CEM-101 stepping down to oral CEM-101. All of these trials will
be randomized, double-blinded studies conducted against a comparator drug
agreed upon with the FDA, for which we will have to show non-inferiority from
an efficacy perspective and acceptable safety and tolerability. The FDA has
recently proposed clarifying the guidance for the clinical development of
therapies for the treatment of CABP. We have designed our Phase 3 trials to
meet these new guidelines. We are planning to finalize our proposed pivotal
trial program with the FDA at our end of Phase 2 meeting for oral CEM-101,
which we expect will occur in the second quarter of 2012. After completing our
end of Phase 2 meeting, we expect to begin the Phase 3 trial with oral CEM-101
in the second half of 2012. We are currently conducting a Phase 1 trial for the
IV formulation of CEM-101, which we expect to complete in the third quarter of
2012. We anticipate that the next trial for the IV formulation of CEM-101 will
be a Phase 3 IV-to-oral trial. In addition, we also plan to initiate a small
Phase 2 trial of oral CEM-101 in patients with bacterial urethritis in 2012.
Taksta: An Oral Therapy for S. aureus, including MRSA, in prosthetic joint
infections and ABSSSI
Taksta is an oral therapy that we are developing in the U.S. for the treatment
of chronic and acute staphylococcal infections caused by S. aureus, including
MRSA, such as prosthetic joint infections and ABSSSI. Taksta is a novel and
proprietary oral dosing regimen of fusidic acid, which is an antibiotic that
has been approved and sold for several decades in Europe and other countries
outside the U.S. and has a long-established safety and efficacy profile, but
has never been approved in the U.S. We believe Taksta has the potential to be
used in hospital and community settings on both a short-term and chronic basis.
Since prosthetic joint infections and ABSSSI are primarily treated with a
combination of IV and oral drugs, we believe that Taksta would enable out-
patient treatment of many patients who would otherwise require hospitalization,
which would provide pharmacoeconomic advantages to health care systems, be well
received by doctors and be more convenient for patients. Based on its safety
profile, the established use of fusidic acid outside the U.S. as a treatment
for chronic infections and the lack of effective oral antibiotics that can be
taken for long periods of time, we believe that there is a significant market
opportunity for Taksta among patients requiring long-term antibiotic treatment,
such as patients with prosthetic joint infections. We have filed a patent
application for our proprietary loading dose regimen. In addition, Taksta is
eligible for market exclusivity under the Drug Price Competition and Patent
Term Restoration Act, also known as the Hatch-Waxman Act. If approved for
prosthetic joint infections, Taksta could be eligible for orphan drug status
in the U.S., which would provide seven years of exclusivity.
According to a survey of physicians conducted by Decision Resources, MRSA is
the most important pathogen of concern in patients with osteomyelitis, or bone
infection, and prosthetic joint infection. These infections often begin with
skin infections where bacteria enter the bloodstream through breaks in the
skin or mucous membrane that occur as a result of a wound or due to a surgical,
medical or dental procedure. According to the Infectious Diseases Society of
America, or IDSA, MRSA infections account for approximately 60% of skin
infections seen in U.S. emergency rooms. Among the most common current
treatments for osteomyelitis, prosthetic joint infections and ABSSSI with MRSA
are vancomycin (available as a generic) and daptomycin (sold under the brand
name Cubicin®), both of which are available only as IV formulations.
Linezolid is available in both IV and oral formulations, is a treatment for S.
aureus and is the only oral antibiotic approved by the FDA for MRSA. Linezolid
is also prescribed for osteomyelitis, prosthetic joint infections and ABSSSI
with MRSA. Linezolid, however, has significant side effects and its use
requires additional monitoring in certain patient populations, including
patients who are on serotonergic drugs such as selective serotonin reuptake
inhibitors, or SSRIs (such as Prozac® , Paxil® and Zoloft®). According to
IMS Health and public pharmaceutical company filings, in 2010 linezolid,
vancomycin and daptomycin generated an aggregate of over 900,000 prescriptions
and aggregate sales of $1.8 billion in the U.S.
Our Phase 1 and Phase 2 clinical trials and pre-clinical studies to date, as
well as historical data from outside the U.S., have shown that Taksta has the
following attributes:
• An established safety profile outside the U.S. : Fusidic acid has been
approved and used in certain countries in Europe and other countries
outside the U.S. for many years, including in some countries for as many
as 40 years, both for short-term use in complicated skin infections as
well as for use in other types of infections requiring long-term
therapy, including prosthetic joint infections and osteomyelitis.
• Comparable efficacy to the only FDA-approved oral treatment for MRSA :
In a recently completed Phase 2 trial in 155 ABSSSI patients comparing
Taksta to linezolid, Taksta successfully demonstrated efficacy
comparable to linezolid and confirmed its effectiveness against S.
aureus, including MRSA. MRSA has been identified by physicians as the
most important pathogen of concern in patients with osteomyelitis and
prosthetic joint infection. We have also conducted in vitro tests of
Taksta’s activity against thousands of strains of S. aureus found in the
U.S. and our data show that virtually all of the strains tested (99.6%)
are susceptible to Taksta.
• Ability to be used orally as a treatment for all types of S. aureus,
including MRSA : We believe, based on our clinical studies and
historical data on fusidic acid, that Taksta has the potential to be a
safe and effective oral treatment for prosthetic joint infections and
ABSSSI caused by MRSA. We believe Taksta would enable physicians to
treat patients not otherwise needing hospitalization on an out-patient
basis, thereby reducing costs and avoiding the unnecessary introduction
of resistant bacteria into the hospital setting. Linezolid is the only
oral drug currently approved for use against MRSA; however, its use is
associated with serious side effects and is not recommended for certain
patient populations without additional monitoring.
• Lower frequency of resistance development due to our loading dose
regimen: Our studies have shown that our proprietary loading dose
regimen, which delivers a dose of Taksta on the first day of treatment
that is higher than on all subsequent days, minimizes the development of
resistance to Taksta by increasing the amount of drug initially
delivered to the bacteria.
• Potential to be used in patient populations not well served by current
treatments : Due to its established safety and tolerability profile
outside the U.S., we believe Taksta could also be used for patients that
are anemic, as well as patients on serotonergic drugs, such as SSRIs,
who could be treated with an oral antibiotic, but for whom linezolid may
not be a convenient treatment option due to additional monitoring
requirements. In addition, chronic staphylococcal infections require
long-term therapy. Linezolid is not recommended to be used for longer
than 14 days without additional monitoring because of the increased
possibility of side effects, limiting its use in long-term or chronic
treatment. Long-term use of vancomycin or daptomycin also poses safety
concerns and is impractical because these treatments are only available
in IV formulations. We believe Taksta could fulfill the need for a safe,
long-term oral therapy to treat chronic infections such as prosthetic
joint infections and osteomyelitis.
We have successfully completed a Phase 2 clinical trial with Taksta in ABSSSI
patients. In this trial, the Taksta loading dose regimen demonstrated efficacy,
safety and tolerability that was comparable to linezolid. We expect to initiate
a Phase 2 trial in patients with prosthetic joint infections in the fourth
quarter of 2012.
Platform and Pre-Clinical Programs
Our earlier-stage programs include the development of CEM-101 and Taksta for
other uses, as well as the development of newly discovered compounds as
antibiotics and for the treatment of other diseases. Given the spectrum,
potency and resistance profile of CEM-101, we plan to initiate a small open-
label Phase 2 trial for oral CEM-101 as a treatment for bacterial urethritis
in early 2012. In the future we may pursue secondary indications for CEM-101 to
treat other respiratory tract infections such as pharyngitis, sinusitis and
chronic bronchitis, as well as other infectious diseases such as otitis media
(middle ear infection), Helicobacter gastritis, malaria, tuberculosis, eye
infections, infections in cystic fibrosis, or CF, patients and chronic
obstructive pulmonary disease, or COPD. The successful use of fusidic acid
outside of the U.S. leads us to believe that Taksta could be used to treat
other chronic infections such as osteomyelitis and infections related to CF,
all of which tend to require long-term or chronic treatment. In addition to
CEM-101 and Taksta, we have a library of over 500 macrolide compounds, which,
when combined with our chemistry expertise, provides us with a platform for
developing future product candidates. Our management has extensive experience
in developing antibiotics and some members have been part of leadership teams
that have successfully taken one or more antibiotics to FDA approval.
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We were formed as Cempra Holdings, LLC, a limited liability company under the
laws of the State of Delaware, on May 16, 2008. Cempra Holdings, LLC was formed
in connection with a reorganization whereby the stockholders of Cempra
Pharmaceuticals, Inc., a corporation formed under the laws of the State of
Delaware on November 18, 2005, exchanged their shares of Cempra
Pharmaceuticals, Inc. stock for shares of Cempra Holdings, LLC, pursuant to a
merger of a subsidiary of Cempra Holdings LLC with and into Cempra
Pharmaceuticals, Inc., as a result of which Cempra Pharmaceuticals, Inc. became
a wholly-owned subsidiary of Cempra Holdings, LLC. Prior to the closing of this
offering, we will complete a corporate conversion pursuant to which Cempra,
Inc. will succeed to the business of Cempra Holdings, LLC and its consolidated
subsidiaries and the shareholders of Cempra Holdings, LLC will become
stockholders of Cempra, Inc.
Our primary executive offices are located at 6340 Quadrangle Drive, Suite 100,
Chapel Hill, NC 27517-8149, and our telephone number is (919) 313-6601. Our
website address is www.cempra.com.