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| 8-K - 8-K - MELINTA THERAPEUTICS, INC. /NEW/ | d549319d8k.htm |
 Developing Well-
Differentiated Antibiotics
to Meet Medical Needs
Cempra Corporate
Presentation
Prabhavathi Fernandes, Ph.D.
June 2013
Exhibit 99.1 |
 Forward Looking Statement
2
This presentation contains forward-looking statements regarding future events. These
statements are just predictions and are subject to risks and uncertainties that could cause
the actual events or results to differ materially. These risks and uncertainties include, among
others: risks related to the costs, timing, regulatory review and results of our studies and
clinical trials; our and our strategic partners’ ability to obtain FDA and foreign regulatory
approval of our product candidates; our dependence on the success of Solithromycin and
TAKSTA; our need to obtain additional funding and our ability to obtain future funding on
acceptable terms; our anticipated capital expenditures and our estimates regarding our
capital requirements; the possible impairment of, or inability to obtain, intellectual property
rights and the costs of obtaining such rights from third parties; the unpredictability of the size
of the markets for, and market acceptance of, any of our products, including Solithromycin
and TAKSTA; our ability to produce and sell any approved products and the price we are
able to realize for those products; our ability to retain and hire necessary employees and to
staff our operations appropriately; our ability to compete in our industry; innovation by our
competitors; and our ability to stay abreast of and comply with new or modified laws and
regulations that currently apply or become applicable to our business. Please refer to the
documents that we file from time to time with the Securities and Exchange Commission. |
 Highlights
Cempra is developing two highly differentiated antibiotics
Safe antibiotics with oral and intravenous formulations and the right spectrum of
activity that are differentiated
have
historically
been
blockbuster
products,
e.g.
Biaxin®,
Z-Pak®,
Cipro®,
Levaquin®, Amoxacillin
Large market opportunity -
Global antibiotic sales in multibillions
Recurring and significant need for new treatments due to resistance and
tolerability issues Strong management team with extensive successful
experience Azactam, Biaxin, Tosufloxacin, Fidaxomicin, Cefdinir, Viread,
Abelcet, others. 3
Solithromycin -
Potent 4
generation macrolide
First Oral and IV macrolide for
monotherapy in CABP
Suspension for pediatrics
Potential for broad pediatric use
TAKSTA –
Long history of use in EU for Prosthetic Joint Infections (PJI)
US development for oral, long-term
treatment of PJI to replace long-term
IV and multiple surgeries
Exclusivity –
Patent issued & Hatch
Waxman & GAIN expected
th |
 Recent
Corporate Developments Solithromycin clinical development
update Phase
3
Oral,
CABP
study
-
enrolling
—
data
expected
in
mid
2014
Phase
3
ready
for
Intravenous-oral
step
down
study
–
initiation
expected
in
4Q
13
Phase
2
study
in
bacterial
urethritis/gonorrhea
–
100%
successful
cure
in
patients
with
culture
proven
gonorrhea
BARDA
(HHS)
funding
drug
development
for
Solithromycin
-
potential
for
5
years
for
bioterror
infections,
pediatric
and
special
population
to
regulatory
approval
Partnership—Japan market for solithromycin exclusively licensed to Toyama,
subsidiary of FUJIFILM Holdings Corp.
TAKSTA clinical development update
Phase
2
PJI
study
enrolling
–
interim
data
expected
by
EOY
2013
Loading
dose
patent
issued-
May
2013
Regulatory development: The GAIN Act
Provides patent term extension for new antibacterials
Priority review for Qualified Infectious Disease Product
4 |
 Product
Indication
Formulation
Preclinical
Phase 1
Phase 2
Phase 3
CEM-101
(Solithromycin)
Community
Acquired Bacterial
Pneumonia (CABP)
Oral
IV-to-Oral
Oral Suspension/
Pediatric
Biodefense
Animal Rule
Urethritis
Oral
TAKSTA
Fusidic Acid
Acute and Chronic
Treatment of Staph
(MRSA)
Oral –
Chronic
Prosthetic Joint
Infections
Oral –
ABSSSI
Oral Suspension/
Pediatric
Cempra’s Antibiotic Portfolio
5
Planned
4Q 2013
Phase 3
ready
TM |
 Solithromycin (CEM-101)
6
Pneumococcal infections cause more deaths per year in U.S. than breast
or prostate cancer
Xu. et al. Deaths: Final Data for 2007. Natl Vital Stat Rep. 2010; 58:
1-51. Forecasts of increases in respiratory disease incidence in
growing numbers of COPD and asthma patients
Drug Discovery News, May 2012.
A Next Generation Macrolide For Respiratory Tract
Infections, Including CABP, in Phase 3 |
 Current and Future Treatment of CABP
7
Indication
Treatment
Implication
Hospital/IV 7–10 days
A Fluoroquinolone
or
Ceftriaxone plus
Azithromycin |
 Developing Differentiated Antibiotics
in a Large Market to Meet Increasing Need
Macrolides are the most widely prescribed
treatment
for
CABP
and
other
RTIs-
>
60%
of
market
Global Antibiotic Sales in 2009
Total $42B
At least 40% of pneumococci in the U.S.
are resistant to azithromycin (Z-Pak).
Jones RN. DMID 2013, 75: 107-109
Pneumococcal resistance rate in
China
–
96.4%.
Kim,
SH,
AAC.
2012;
56:
1418-1426.
Pneumococcal pneumonia is
the No. 1 cause of death from
an infection
From B. Hamad, IMS Health, Nature Drug Discovery, 2010, 9: 675-676.
8
$11.9B
$11.5B
$7.1B
$4.8B
$4B
$2.6B
Cephalosporins
beta-lactams
Fluoroquinolones
Macrolides
Other antibacterials
Tetracyclines /
aminoglycosides
Resistance
Adverse events/lack of tolerability
Inappropriate spectrum
Lack of IV-oral –
step-down treatment
Lack of pediatric dosing formulation
Broad spectrum of activity
Good safety
Excellent tissue/intracellular distribution and anti-
inflammatory activity
Increasing need for new antibiotics driven
by: |
 Gram
Positive
Negative
Positive
Atypical
Atypical
Atypical
Organisms
Solithromycin
Azithromycin
Cephalosporin
Fluoroquinolone
Solithromycin –
Spectrum of Activity
that Addresses CABP Pathogens
Solithromycin (CEM-101) has class leading potency and spectrum in vitro
against CABP pathogens
9
Interacts with bacterial ribosome at three sites –
resistance could only occur if
mutations occur at three distinct sites
Streptococcus
pneumoniae
Haemophilus
influenzae
Staphylococcus
aureus
Legionella
pneumophila
Mycoplasma
pneumoniae
Chlamydophila
pneumoniae |
 First Generation Macrolide
Second Generation Macrolide
In
vitro
activity
is
similar. Better PK, acid
stable, fewer GI effects
Third Generation Macrolides, “Ketolides”
More potent than 2
nd
generation macrolides
Active against macrolide-resistant strains,
2 binding sites, acid stable, good PK, better
tissue distribution
Telithromycin –
major adverse events
Others have failed –
no other new macrolides
Resistance
is
now
widespread
Fourth Generation Macrolide, Fluoroketolide
More potent than 3
rd
generation macrolides
Active against 1
st
, 2
nd
and 3
rd
generation
macrolide-resistant strains, 3 ribosomal
binding sites, extended spectrum, good PK
and tissue distribution, intravenous and
oral dosing
Effective in Phase 2 oral and well-tolerated
Solithromycin
History of Macrolide Development
10 |
 Solithromycin –
Comparable Efficacy and
Favorable Safety to Levaquin –
Oral Phase 2 Trial
Randomized 132 patients received either:
Solithromycin (800 mg day 1, 400 mg days 2–5) or
Levofloxacin (750 mg days 1–5)
11
*Early
Clinical
Response
Proposed
by
FDA,
November
2011
for
future
CABP trial design
Solithromycin demonstrated a favorable safety and tolerability
profile, with a lower incidence of AEs than Levaquin
Population
Solithromycin
Levofloxacin
Success Rate, %
Success Rate, %
Early Clinical Response in ITT*
72.3
71.6
Success at TOC in ITT
84.6
86.6
Success at TOC in mITT
77.8
71.4 |
 Solithromycin –
Intravenous Development
First Injectable Macrolide in 20 Years
Intravenous macrolides have not been developed because of safety
and
tolerability issues
–
FDA
interest
in
IV
dose
–
Allows
enrollment
of
PORT
III
–
IV
patients
Intravenous and oral formulation could allow:
–
Pharmacoeconomic advantage -
Flexibility for initiating treatment in hospital and
step-down oral therapy
Phase 3 intravenous –
oral expected to start 4Q 2013
–
400 mg dose up to 7 days
12
High plasma levels after IV
administration to address
the most resistant bacteria
Well-tolerated
No QT effects
0
4
8
12
16
20
24
Time (h)
10000
1000
100
10
400 mg IV
400 mg Oral |
 Solithromycin: Phase 3 CABP Studies
13
Two Phase 3 trials for NDA
–
–
FDA
CABP
guidance
published
–
design
and
size
consistent
with
guidance
Phase 3 Oral protocol discussed and approved by FDA
Phase
3
oral,
initiated
in
December
2012
–
enrolling
–
–
–
EOP2 meeting results expected to be announced in 2Q 2013
Comparator Avelox (moxifloxacin) – a fluoroquinolone that is used worldwide at same dose Global study – Plan to enroll ~800 patients Top Line results expected in mid 2014 Phase 3 study 1: Oral study currently enrolling Phase 3 study 2: Intravenous- to step down oral,
planned 4Q 2013 |
 Solithromycin’s Broad Use Potential
14
HAP, Simple RTI’s, Pharyngitis, Sinusitis, Bronchitis,
Acute Exacerbation of Chronic Bronchitis (AECB)
Respiratory Tract Infections (RTI):
Antibacterial & Anti-inflammatory:
COPD, Cystic fibrosis, Panbronchiolitis
Special
Populations
BARDA funded
Pediatrics and Pregnancy
No pediatric drug with broad potential in
development
Infections in pregnancy-
neonatal sepsis
Infections in Utero -
Premature, Cerebral palsy, Autism
Spectrum, safe, oral and
IV drug needed urgently.
Congress mandated
development for unmet
need
Large and chronic use
markets
Decreases corticosteroid
dependence
No. 1 reason to
go to the doctor
Largest use of
antibiotics
Biodefense
BARDA funded
Multiple unidentified pathogens
Anthrax, Tularemia
Sexually
transmitted
diseases
Oral protection, safe,
stable. Addressing
intracellular pathogens
Genital Infections
Major
public
health
crisis
–
Multi
drug
resistance,
no
oral
therapy. Most common reportable infectious diseases
Primary cause of infertility in white women
Infertility, PID
Gonorrhea -
The second
most common reportable
infectious disease
Chlamydia –
Most common
infectious disease
GI & others
Helicobacter gastritis, Campylobacteria, tick and insect
borne diseases, diarrhea, and ophthalmic drops
Primary
Indication
CABP
Gastritis/stomach cancer,
diarrhea. Malaria prophylaxis
and treatment, typhus, Lyme,
Other infections
Opthalamic
Licensing
opportunity
Other infections
Helicobacter gastritis, Campylobacteria, tick and insect
borne diseases, diarrhea, and ophthalmic drops
|
 Exclusive
license
in
Japan
to
Toyama
Chemical
Co.,
Ltd.
–
subsidiary
of
FUJIFILM
Total
antibiotic
market
in
Japan
in
approximately
$4B
–
The
second
largest
antibiotic
market. Japan macrolide sales are > $700MM (IMS)
Partnered for Development
15
Global Development Program
North America
Europe & ROW
Toyama is a leading antibacterial company in Japan
–
Currently markets antibacterials for adults and pediatrics
Toyama will commit significant resources to solithromycin development and
commercialization
–
Upfront: $10MM, milestones: $60MM
–
Double digit royalties, subject to reaching sales/contract levels
Japan |
 BARDA
Contract Could Expand Future Indications 16
BARDA contract mitigates development risk, while expanding possible indications to
include biothreat pathogens, pediatrics and special populations
BARDA contract is for a two base year period with guaranteed funding of $17.7
million and is extendable up to five years bringing the potential value of
the total contract to $58 million. NDA
NDA
Adult Approval
Potential
Pediatric
Approval
Biodefense
Approval
1
2
Earlier access to a treatment for a range of
biothreat pathogens for all populations
including pregnant/nursing women and
children in 3 years
Pediatric Drug Development
Required by Law. FDASIA Jan
2013, extension to PREA
Safe and effective drugs for
pediatrics and in pregnancy are
urgently needed
Pediatricians, Ob/Gyn familiar
with macrolides
Additional 6 months exclusivity
NDA
Ph 3 oral –
Adult CAP
Ph 3 IV-Oral–
Adult CAP
Ph 1–
Pediatrics
Animal Rule Studies |
 Expanding Solithromycin Use: Gonorrhea
Studies
Intramuscular ceftriaxone current
treatment
Cephalosporin
allergic
patients
–
No
good options
No oral drug to treat partners
Major public health crisis
Phase 2, Culture negative cure in
100% (all body sites) of evaluable
patients
No other new antibiotic is in clinical
development –
the second most
common communicable disease
Could meet a major public health
need –
Phase 3 ready
17
AUGUST 7, 2012
Feds eye new strategies as gonorrhea fears rise
By Cheryl Wetzstein. Faced with evidence that anti-
gonorrhea drugs are slowly losing their effectiveness,
the federal government is poised to announce new
treatment guidelines later this week to combat the long-
dreaded sexually transmitted disease
Oral Cephalosporins No Longer a Recommended
Treatment for Gonooccal Infections
Gonococcal Surveillance project, US. 2006-2011.
2006
2007*
2008*
2009
2010
2011
†
0
0.5
1.0
1.5
2.0
2.5
Cefixime
Ceftriaxone
Year |
 TAKSTA™
(Fusidic Acid)
18
An Oral Antibiotic for MRSA Infections
Being Developed for Chronic Use in Prosthetic Joint
Infections in the U.S. |
 What
is TAKSTA™? TAKSTA
Cempra’s proprietary fusidic acid dosing regimen
Fusidic acid approved in Western Europe, Australia, and other countries
40
years
of
established
safety
and
efficacy
profile
in
acute
and
chronic
use
in
staph
infections ex-U.S.
Unique structure, no known cross resistance with any other antibiotic
Orally bioavailable
Targeted against gram-positive pathogens, including MRSA –pathogens that
causes bone and joint infections requiring long-term treatment
Exclusivity
NCE in the U.S.: Hatch Waxman exclusivity, 5 years obtained by Cempra,
exclusive supply agreement of drug substance –a fermentation
product GAIN
Act
adds
an
additional
5
years
of
data
exclusivity
–
A
minimum
of
10
years
of
data
exclusivity or 12 years if Orphan
Loading dose patent Protects U.S. Market Exclusivity to 2029 + patent term
extension 19 |
 Current and Future Treatment of Prosthetic
Joint Infections
20
IV
and
Oral
Antibiotics
–
4–6
Weeks
Debride
and Treat
Surgery
Spacers In
Surgery New
Prosthesis Inserted
Cempra’s
trial
Debride, IV
Vancomycin
for 1–7 Days
Oral Fusidic
Acid Plus Oral
Rifampin for
6–12 Months
Two-stage
Revision
Current U.S.
Treatments
Surgery
Sterile Joint
Potential for cost savings, surgery decrease,
patient comfort and pharmacoeconomic
advantages gain physician, payor acceptance
Cempra Aims To Bring The Lower Cost, More
Effective European PJI Treatment Paradigm to the US
Orthopedic
Surgery |
 TAKSTA Activity Against MRSA in the US
–
Phase 2 Study ABSSSI Study
21
Data from 155-patient Phase 2 trial demonstrates
efficacy and safety in ABSSSI
Comparable efficacy
to Zyvox (linezolid)
Linezolid is contra-indicated in those on SSRIs and not available for chronic
use End of Phase 2 meeting for ABSSSI with FDA completed
Cempra’s proprietary loading dose regimen -
U.S.
patent no. 8,450,300. Issued May 2013
Novel dosing regimen of fusidic acid1500 mg BID loading
dose followed by 600 mg BID maintenance dose
Loading dose regimen validated –
no resistance, well
tolerated in Phase 2 study
500 mg Q8h
1500 mg Q12h on Day 1 x 2 doses
followed by 600 mg Q12h
0
20
40
60
80
100
120
European dosing
Cempra’s loading dose
0
24
48
72
96
120
Time (hrs) |
 |
 Osteomyelitis/Prosthetic Joint Infection
Opportunity
Growing
need
for
oral
therapies
to address MRSA infections in bone
and joint infections
-
Intravenous
vancomycin/daptomycin
treatment for 4–6 weeks is used
currently –
with many patients
requiring life-long treatment and
replacement prosthesis
Fusidic acid is used ex-US as a safe,
oral and effective antibiotic to eliminate
the need for IV therapy and decrease
the need for replacing the prosthesis
23
Total Prosthetic Joint Infections
1990–2004 (Kurtz et al.)
N Engl J Med. 2009; 361: 787-794.
0
1000
2000
3000
4000
5000
6000
7000
Infected total knee
arthroplasty
Infected total hip
arthroplasty
Cempra is developing fusidic acid in a new proprietary dosing
regimen for long term use in PJI in the U.S. |
 PJI Facts:
200,000 Hip Replacements; 550,000 Knee Replacements in 2007 (3% increase/yr)
1% of hips and 2% of knees develop PJI's
Total
Joint
and
Hardware
Procedures
–
3,286,000/year
a,b
Potential use in osteomyelitis, septic arthritis, and diabetic foot
TAKSTA for Chronic Use in Prosthetic Joint
Device (PJI) Infections
Two compassionate use cases of bone/prosthesis infections in North America
24
a
Life
Science
Intelligence
market
research
report.
U.S.
Markets
for
Large
Replacement
Technologies
in
2012.
March,
2012.
b
Life
Science
Intelligence
market
research
report.
U.S.
Markets
for
Small
Joint
Implants
and
Hardware
for
the
Extremities.
January,
2012.
Cempra’s Phase 2 study, initiated in December 2012 -
enrolling
•
Efficacy is comparable
to linezolid
•
Useful for oral chronic
use in all patient
populations
Safety
TAKSTA
Linezolid |
 Projected Milestones
2013 Milestones
2Q 13: Partnered in Japan –
Part of global development program
2Q 13: BARDA partnership for Pediatrics, Special populations and biodefense
2Q 13: Loading dose patent for TAKSTA issued
2Q 13: Solithromycin Phase 2 gonorrhea trial complete; Phase 3 ready
2Q 13: EOP2 FDA meeting minutes for NDA requirements
4Q 13: Solithromycin initiation of Phase 3 IV-to-Oral CABP Trial
EOY 13: TAKSTA interim Phase 2 Prosthetic Joint Infection results
2014 Milestones
Mid 2014: Solithromycin Phase 3 Oral CABP data expected
25 |
 Cash & Equivalents (at 3/31/13)
$60M*
Long-Term Debt (at 3/31/13)
$9.9M
Shares Outstanding (5/31/13)
24.9M
Market Capitalization (5/31/13)
$200M
Capitalization
26
* Does not include the upfront payment of $10MM from Toyama Chemical Co. Ltd.
|
 Proven Management Team
27
Gary Horwith, MD
EVP Regulatory
Carl Foster
EVP Business Development
Mark Hahn, CPA
CFO
David Oldach, MD
SVP Clinical
Prabhavathi Fernandes, PhD
President & CEO
David Pereira, PhD
SVP Chemistry
Azactam (aztreonam)
Biaxin (clarithromycin)
Dificid (fidaxomicin)
Plenaxis (abarelix)
Zavesca (miglustat)
OncoVax
Prilosec (omeprazole)
IPO and M&A
Athenix-Bayer CropScience
Charles & Colvard (CTHR)
E&Y
S,
aureus
vaccine
Abelcet
Viread
GS-9190
Combinations against HCV
Injectable Penicillins
Dobutamine HCl Injection
Ranitidine Injection |