UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
Form 8-K
Current Report
Pursuant to Section 13 or 15(d) of The
Securities Exchange Act of 1934
Date of Report (Date of earliest event reported): February 15, 2012
MEDICINOVA, INC.
(Exact name of registrant as specified in its charter)
| DELAWARE | 001-33185 | 33-0927979 | ||
| (State or other jurisdiction of incorporation) |
(Commission File Number) |
(I.R.S. Employer Identification No.) |
| 4350 LA JOLLA VILLAGE DRIVE, SUITE 950, SAN DIEGO, CA |
92122 | |||
| (Address of principal executive offices) | (Zip Code) | |||
Registrant’s telephone number, including area code: (858) 373-1500
Not applicable.
(Former name or former address, if changed since last report.)
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions (see General Instruction A.2. below):
| ¨ | Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425) |
| ¨ | Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12) |
| ¨ | Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b)) |
| ¨ | Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c)) |
| Item 8.01 | Other Events. |
On February 15, 2012, MediciNova, Inc. (the “Company”) updated the slide presentation to be used by the Company at investor meetings. A copy of the revised slide presentation is attached hereto as Exhibit 99.1 and is incorporated herein by reference.
| Item 9.01 | Financial Statements and Exhibits. |
| (d) | Exhibits. |
| Exhibit No. |
Description | |
| 99.1 | Slide presentation of the Company. | |
SIGNATURE
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
| MEDICINOVA, INC. | ||
| By: |
/s/ Michael Coffee | |
| Michael Coffee | ||
| Chief Business Officer | ||
Date: February 15, 2012
EXHIBIT INDEX
| Exhibit No. |
Description | |
| 99.1 |
Slide presentation of the Company. | |
 ©
MediciNova, Inc. 2012
Accelerating
the global development
and commercialization of
innovative pharmaceuticals
Exhibit 99.1 |
 ©
MediciNova, Inc. 2012
Forward-Looking Statements
Statements in this presentation that are not historical in nature constitute forward-looking
statements within the meaning of the safe harbor provisions of the Private Securities Litigation
Reform Act of 1995. These forward-looking statements include statements regarding
MediciNova’s clinical trials supporting the safety and efficacy of its product candidates
and the potential novelty of such product candidates as treatments for disease, plans and objectives for
clinical trials and product development, strategies, future performance, expectations, assumptions,
financial condition, liquidity and capital resources. These forward-looking statements may be
preceded by, followed by or otherwise include the words "believes," "expects,"
"anticipates," "intends," "estimates," "projects," "can," "could," "may," “will,”
"would," or similar expressions. Actual results or events may differ materially from those
expressed or implied in any forward-looking statements due to various factors, including the
risks and uncertainties inherent in clinical trials and product development and
commercialization, such as the uncertainty in results of clinical trials for product candidates,
the uncertainty of whether the results of clinical trials will be predictive of results in later stages
of product development, the risk of delays or failure to obtain or maintain regulatory approval,
the risk of failure of the third parties upon whom MediciNova relies to conduct its clinical
trials and manufacture its product candidates to perform as expected, the risk of increased cost
and delays due to delays in the commencement, enrollment, completion or analysis of clinical
trials or significant issues regarding the adequacy of clinical trial designs or the execution of clinical trials
and the timing, cost and design of future clinical trials and research activities, the timing of
expected filings with the FDA, MediciNova’s failure to execute strategic plans or strategies
successfully, MediciNova’s collaborations with third parties, MediciNova’s ability to
integrate its two ibudilast development programs and to pursue discussions with potential
partners to secure a strategic collaboration to advance the clinical development of the combined development
program, the availability of funds to complete product development plans and MediciNova’s ability
to raise sufficient capital when needed, or at all, MediciNova’s ability to comply with the
covenants in its financing agreements, intellectual property protection, and the other risks and
uncertainties described in MediciNova’s filings with the Securities and Exchange Commission,
including MediciNova’s annual report on Form 10-K for the year ended December 31, 2010
and its subsequent periodic reports on Forms 10-Q and 8-K. You are cautioned not to place undue
reliance on these forward-looking statements, which speak only as of February 14, 2012. MediciNova
disclaims any intent or obligation to revise or update these forward-looking statements.
|
 ©
MediciNova, Inc. 2012
MediciNova Overview:
•
Founded in September 2000
•
Headquartered in San Diego, CA, with an additional office in Tokyo, Japan
•
Dual listing on NasdaqGM as MNOV
and Osaka Securities Exchange as 4875
•
$39.2 million market cap (NasdaqGM) as of 2/14/2012 (aggregate value of 18.3 million
shares outstanding of common + preferred on an as converted basis)
In-Licensed Clinical Stage Compounds:
•
Unique access to differentiated, potentially high-value assets primarily from
Japanese alliances (Kissei, Kyorin, Mitsubishi Tanabe Pharma, Meiji)
New Approaches to Treat Serious Medical Conditions:
•
Bedoradrine Sulfate (MN-221): Intravenous (IV)
treatment for exacerbations of asthma
and chronic obstructive pulmonary disease (COPD)
•
Ibudilast (MN-166/AV411): Oral treatment for progressive
multiple sclerosis, neuropathic pain, and drug addiction
3
Corporate Overview:
MediciNova, Inc. |
 ©
MediciNova, Inc. 2012
4
In-License:
•
Novel, small-molecule product candidates with significant
clinical or preclinical data packages
and attractive market opportunities Conduct Proof-of-Concept Clinical
Trials: •
Conduct Phase 1 and Phase 2 clinical trials to
demonstrate safety and efficacy of compound
Two Pathways After Phase 2 (Proof-of-Concept):
1.
Internal development of compound towards commercialization in
North America
2.
Seek partnership for further development of compound ex U.S.
Business
Model:
Return On Investment |
 ©
MediciNova, Inc. 2012
Product Candidates
Preclinical
Phase 1
Phase 2
Phase 3
Bedoradrine Sulfate (MN-221) Program
Acute Exacerbations of Asthma
Exacerbations of COPD
Preterm Labor
Ibudilast (MN-166/AV11) Program
Progressive Multiple Sclerosis
Neuropathic Pain
Drug Addiction
Asthma, IC, Cancer, GAD, OAB, Thrombosis
Commercially-Attractive
Diversified Portfolio
5
Non-Core
Programs
(Various stage of development –
available for out-licensing) |
 ©
MediciNova, Inc. 2012
6
Significant Milestones
*Anticipated completion dates based on current projections
**Tentative based on availability of non-dilutive financing
Milestone:
Timeline*:
Complete an Equity Raise ($~7.9M net)
1Q, 2011
Commence Enrollment in Phase 1 Ibudilast trial for Meth. addiction
2Q, 2011
Sign Chinese Joint-Venture for MN-221
2Q, 2011
Commence Enrollment in Phase 2 Ibudilast trial for MOH Pain
3Q, 2011
Complete Equity Raise and Funding from Kissei ($10M)
4Q, 2011
Top-line Results from Phase 2b MN-221 CL-007 Acute Asthma Trial
1Q, 2012
Top-line Results from Phase 1b Multi-Dose Trial in COPD
2Q, 2012
Plan to Initiate Phase 2b Clinical Program for Ibudilast (MS /Pain)
2H, 2012** |
 MN-221:
•
Acute Exacerbations of Asthma
•
Exacerbations of COPD |
 ©
MediciNova, Inc. 2012
8
Acute Exacerbations of Asthma (AEA)
Definition:
•
Long-lasting and severe asthma episode that is not responsive to initial
bronchodilator or corticosteroid therapy
Market Opportunity*:
•
Approximately 1.9 million annual emergency room visits in the U.S.
•
~500,000 annual hospitalizations in U.S. (~560,000 in
UK/Spain/Germany/France/Italy) •
Average length of stay for asthma hospitalization is 3.3 days
•
Average cost for asthma hospitalization is $6,477
Current Standard of Care (SOC):
•
Inhaled beta agonists, inhaled anticholinergics, and IV or oral corticosteroids
•
Current
Treatments
are
limited
by
Bronchoconstriction
(Insufficient
air
flow
due
to
inflammation
and
airway
constriction
prevents
inhaled
drug
uptake
in
the
lungs)
and
Mucus
Plug Formation
(Persistent airflow limitation due to mucus secretion
*Source: National Center for Health Statistics / CDC, WHO website, “Core
Health indicators”, 2007 National Hospital Discharge Survey, IMS
Health’s
Disease
and
Condition
Benchmarks
–
PharMetrics
Integrated
Database,
1/2007
–
12/2008 |
 ©
MediciNova, Inc. 2012
9
A COPD exacerbation
is a sustained worsening of the
patient's condition, from the stable state and beyond
normal day-to-day variations, that is acute in onset.
COPD exacerbations are associated with a significant
increase in mortality, hospitalization and healthcare
utilization.
COPD Exacerbations
COPD patients are generally more ill than asthmatics with
overall higher hospitalizations and mortality.
COPD
Discharged
Hospitalized
72%
28%
1,900
Asthma
52%
48%
1,500
Hospitalization rates amongst
Asthma and COPD patients
Thousands
Source: CDC, CDC COPD surveillance in U.S. 2000; US Census; American Lung
Association website *For
COPD
pts.
with
anemia;
for
pts.
w/o
anemia
the
stay
is
~5.8
days
at
a
cost
of
~$25K
1.5 million hospital emergency department visits
765,000 hospitalizations
Average length of stay 7.4 days*
Average cost ~$32,000*
119,000 deaths |
 ©
MediciNova, Inc. 2012
MN-221: A novel, highly selective -
adrenergic receptor agonist
Potential advantages over current therapy:
1.
Improved Efficacy
•
Route of administration (IV vs. inhalation)
2.
Improved Safety
•
High selectivity for receptor versus
•
Partial agonist for
receptor*
3.
Reduced Health Care Expenses
•
Reduction in hospitalizations
10
MN-221: A New Approach to Treating
Acute Exacerbations (Asthma & COPD)
receptors are primarily responsible for cardiovascular stimulation
|
 ©
MediciNova, Inc. 2012
*Source: Weber, Silverman et al,
American Journal of Medicine, 2002,
Volume 113; pp 371
11
Acute Asthma Treatment Flow in
Emergency Departments (EDs) in the U.S.
965,000
935,000
935,000
410,000
525,000
525,000
Input:
1,900,000 patients
with acute
exacerbations of
asthma present at
U.S. EDs annually
1
st
line therapy in ED:
Patients receive SOC,
many while in the
waiting room
2
nd
line therapy in ED:
Patients who do not
initially respond continue
receiving SOC
Large Market
Opportunity for MN-221
1,900,000
1,900,000
Hospitalization:
Patients who do not
respond to SOC are
eventually hospitalized
COST ~ $6,477/patient
Patients who respond
to initial therapy and
are discharged
Patients who
eventually respond to
standard therapy and
are discharged |
 ©
MediciNova, Inc. 2012
•
Randomized, placebo-controlled, double-blind, multi-center
Phase 2 clinical trial
•
Up to 170 -
200 patients with severe, acute exacerbations of asthma
(FEV
1
50% predicted) at multiple US emergency department sites
•
Two treatment groups of up to 85-100 patients/group
•
1,200µg infusion of MN-221 over 1hr (600µg in first 15 minutes
followed by 600µg in next 45 minutes) + Standard-of-Care
•
Standard-of-Care alone + placebo infusion
Enrollment almost complete; top-line results expected 1Q, 2012
MN-221-CL-007:
Ongoing Phase 2b Trial
12 |
 ©
MediciNova, Inc. 2012
MN-221 CL-007
Efficacy Endpoints
13
MN-221
Asthma Clinical Endpoints
for CL-007 Phase 2b Trial
1
2
3
FEV
1
Area Under the Curve (AUC) of
the change from baseline in FEV
1
(% predicted) during the 3-hour
Treatment Period
Reduction in Hospital
Admissions
Clearly-recognized Clinical and
Pharmacoeconomic Benefit
Improvement in Clinical
Signs of Asthma
-
Respiratory Rate
-
Accessory Muscle Use
-
Supplemental Oxygen Use |
 ©
MediciNova, Inc. 2012
•
Randomized, placebo-controlled, double-blind, Phase 1b clinical trial
•
20
stable
moderate-to-severe
COPD
patients
(30%
FEV
1
80%)
•
Two treatment groups
•
1,200µg infusions of MN-221 every 12 hours (15 pts.) for 3 days
•
Placebo (5 pts.)
•
Primary
objective
is
to
determine
the
safety
and
tolerability
of
MN-221 compared
to
placebo
when
administered
multiple
times
over
several
days
in
COPD
patients
who may also have co-morbidities
and concomitant medications common in
this population.
•
Secondary endpoint is to evaluate pharmacokinetics and preliminary efficacy of
repeated
administration of MN-221 in COPD patients
Top-line results expected 2Q, 2012
MN-221-CL-012:
Ongoing Phase 1b Trial
14 |
 ©
MediciNova, Inc. 2012
MN-221 Clinical Development
Acute Asthma Program:
•
Multiple doses tested at infusion length of
15min, 1hr, and 2hr
•
Completed 2 trials in asthmatics with
stable disease
•
CL-004
•
CL-005
•
Completed Phase 2a trial in patients with
AEA in the ED
•
CL-006
•
Ongoing Phase 2b proof-of-concept study
in patients with AEA in ED
•
CL-007
•
Phase 3 trials –
N. & S. Hemisphere
COPD Program:
•
Multiple doses tested at 1 hour infusion
•
Completed 1 trial in COPD patients with
stable disease
•
CL-010
•
Initiating screening in multi-dose trial in
patients with stable COPD
•
CL-012
•
Efficacy and Safety data will
also be very useful in further
development of MN-221 for
acute asthma
15
(23
patients)
(17
patients)
(29
patients)
(~170-200
pts.)
(48
patients)
(20
patients) |
 ©
MediciNova, Inc. 2012
MN-221 Potential Development
2012
2013
2014
2015
2011
Other
Indications?
2016 |
 MN-221:
Market Opportunity and
Patent Summary |
 ©
MediciNova, Inc. 2012
18
MN-221 Market Opportunity*
Market
Acute Asthma
COPD
Exacerbations
US
$375-400 million
$380-420 million
Europe
$200-300 million
$200-300 million
Rest of World
$150-250 million
$150-250 million
Worldwide
MN-221 Sales Potential
$725-950 million
$730-970 million
Combined Worldwide
MN-221 Sales Potential
$1.5-1.9 Billion
Source: Physician interviews, team analysis
*Prices in today’s dollars, do not reflect any price increases which may be
implemented *Assumes a conservative price per dose target ~$550/dose
|
 ©
MediciNova, Inc. 2012
19
Pharmacoeconomic
Benefit:
Price of MN-221 vs. % Hospitalizations
Source: Guidepoint Global survey of Medical Directors at U.S. managed care
companies |
 ©
MediciNova, Inc. 2012
MN-221 Patent Summary
•
The U.S. patent for MN-221 has composition of matter and method of use
claims and is set to expire no earlier than February
2017
•
Corresponding composition of matter patents in various other countries
•
U.S. patent expiration does not include Waxman-Hatch patent term
restoration (industry average = 4.5 years)
•
Waxman-Hatch grants 5 years of exclusivity from approval in the U.S. (We
anticipate
this
along
with
pediatric
exclusivity
and
ANDA
review
time
will
give
us at least 7.0 years of exclusivity)
•
Exclusivity in Europe is 10 years for first approval of new chemical entities
•
In addition, MediciNova has filed multiple patent applications related to
MN-221 which if granted, could protect MN-221 until at least 2030
20 |
 Ibudilast
(MN-166/AV-411): •
Progressive Multiple Sclerosis
•
Neuropathic Pain
•
Addiction |
 ©
MediciNova, Inc. 2012
22
Ibudilast
•
Oral administration
•
Safe and well tolerated
•
Approved in Japan/Korea over 3.2M patient exposures
•
>420 subjects treated with ibudilast
•
Dosing up to 100 mg single dose
•
Mechanism(s) of action primarily:
•
Inhibition of macrophage Migration Inhibitor Factor (MIF)
•
PDE-4,10 inhibition
•
Attenuation of glial cell activation
Clinical Safety & Preliminary Efficacy Established
•
Phase 2 multiple sclerosis proof-of-concept study
•
Efficacy on disease progression endpoints validated at 60 mg/d
•
Phase 1 dosing to 100 mg/d
•
Phase 1b/2a trial in diabetic neuropathic pain
•
Phase 1b/2a clinical trial in opioid withdrawal & analgesia
Ibudilast Overview |
 ©
MediciNova, Inc. 2012
1Q 2012
2Q 2012
3Q 2012
4Q 2012
Ibudilast (MN-166/AV11) Program
Ibudilast (MN-166/AV11) Program
Progressive MS* / Neuropathic Pain*
Phase 2b Trial (POC)
Opioid
Dependence
Columbia University –
Phase 2a Trial
Medication Overuse Headache Pain
Univ. Adelaide –
Phase 2a Trial
Methamphetamine Addiction
UCLA –
Phase 1b Trial
Ibudilast –
Ongoing and Future
Development
23
*Pending Grant / Partner Funding
*Pending Grant / Partner Funding |
 ©
MediciNova, Inc. 2012
•
Collaboration with Development Partner:
1.
Advance to Phase 2b Proof-of-Concept in MS and/or Pain
2.
Provide competitive economics for first in class therapy
3.
Could be collaboration through:
i.
Pharma partner
ii.
Project financing
iii.
Shared-risk with competitive CRO agreement
•
Sustain NIDA-sponsored Drug Addiction Development
•
Potential for Gov’t and MS Society consortium funding of Phase 2 POC Trial
•
Consider Investigator-sponsored Neurological Trials
24
Strategy for Ibudilast’s Development |
 ©
MediciNova, Inc. 2012
25
Patent/Commercial Overview
Method of Use
MS
Neuropathic
Pain
Composition of Matter
AV1013
AV1013
Enantiomer
Key:
Exp. 2018
Exp. 2025
Exp. 2027
MIF Inh.
screen
Exp. 2027
Acute & Sub-
chronic Pain
Addiction
Exp. 2026
Progressive MS
Exp. 2029
Issued or
Allowed
Exp. 2027
Exp. 2028
Pending
MOH Pain
Anxiety -
Traumatic
Brain Injury/PTSD
Ibudilast +
Immunomodulator
for MS
2
nd
Generation
Analogs |
          ©
MediciNova, Inc. 2012
26
Leadership
Years
Experience
Background
Yuichi Iwaki, MD, PhD
Yuichi Iwaki, MD, PhD
CEO & President
35
Professor at USC, formerly Professor at University
of Pittsburgh; Advisor to JAFCO, Tanabe
Michael Coffee
Michael Coffee
Chief Business Officer
26
Avigen, Amarin Corp., Elan Pharmaceuticals, N.A.,
Athena Neurosciences
Kirk Johnson, Ph.D.
Kirk Johnson, Ph.D.
Chief Scientific Officer
21
Avigen, Genesoft Pharmaceuticals, Chiron
Corporation (Novartis -
San Francisco)
Masatsune Okajima, CMA
Masatsune Okajima, CMA
VP, Head of Japanese Office
19
Daiwa Securities SMBC, Sumitomo Capital
Securities, Sumitomo Bank
Kazuko Matsuda, M.D., Ph.D., MPH
Kazuko Matsuda, M.D., Ph.D., MPH
Chief Medical Officer
20
Assistant Professor USC, Keck School of Medicine;
Children’s Hospital Los Angeles.
Michael Gennaro, CPA, MBA
Michael Gennaro, CPA, MBA
Chief Financial Officer
37
Partner at FLG Partners, Sylantro Systems, Inverse
Network Technology, Novell, Piiceon, Verticom
Management Team with
Global Experience |
 ©
MediciNova, Inc. 2012
27
Financial Overview
•
~18.3 million shares outstanding of common + preferred on an as converted basis
•
Cash Runway into 2013
•
$2.5 million additional payment from Kissei
•
$7.5 million raised in private stock sale to Kissei Pharmaceutical Co., Ltd.
•
$8.7 million
in
cash
&
cash
equivalents
as
of
9/30/2011
•
Financial Resources:
Kissei purchased 800,000 shares common stock at $2.50/share
Kissei purchased 220,000 shares Series B preferred stock at $25.00/share
(convertible to common at 1:10 ratio)
•
•
MediciNova to expand MN-221 program in asthma and COPD
•
+$10 million
raised
through
equity
sale
and
non-dilutive
funding
by
Kissei
in
4Q,
2011 |
 ©
MediciNova, Inc. 2012
28
MediciNova Corporate Summary
*Anticipated completion dates based on current projections
1.
Top-Line Results from CL-007 Trial
2.
Top-Line Results from CL-012 Trial
3.
Announce Plan for Ibudilast
Raised ~$18M in 2011
Cash Runway into 2013
Clinical development expertise
Strong international presence, especially Japan
Large and small pharma/biotech experience |
 Addendum
Data from Completed Trials
MN-221
Ibudilast (MN-166/AV411) |
 MN-221:
Data from Completed Trials
•Asthma
Program: CL-004, CL-005, CL-006
•COPD
Program: CL-010
•Safety
Review |
 MN-221
Clinical Results Improved Lung Function at
Different Dosing Levels: Stable Asthmatics
31
CL-004: Stable Mild/Moderate Asthmatics
CL-005: Stable Moderate/Severe Asthmatics |
 MN-221
Clinical Results Improved Lung Function and Clinical
Outcome Above and Beyond Standard of Care
(SOC) Mean
change
in
FEV
1
from
baseline
was
5.3%
higher
in
the
MN-221
dose
groups
versus
the
placebo group
MN-221 reduced the hospitalization rate by 45%
32
SOC + placebo
SOC + placebo
14.0%
8.7%
46%
25%
MN
221 + SOC
MN
221 + SOC
-
-
0%
2%
4%
6%
8%
10%
12%
14%
16%
0%
10%
20%
30%
40%
50%
Mean FEV1
Change from Baseline (Hour 5)
MN-221 (all dose groups) + SOC
vs. SOC + placebo
Hospitalization Rate:
MN-221 (all dose groups) + SOC
vs. SOC + placebo
CL-006: Patients Suffering from Acute Exacerbation of Asthma in Emergency
Department |
 33
MN-221 Clinical Results
Improved Lung Function at
Different Dosing Levels: COPD Patients
CL-010: Stable Moderate/Severe COPD Patients |
 •
MediciNova has preclinical data and clinical data which demonstrates the
safety of MN-221.
•
In summary, we have not seen clinically significant safety concerns with
MN-221 and it has been tested in ~300 subject to date.
•
In the ongoing CL-007 trial our Data Safety Monitoring Board has reviewed
safety data for 148 patients with no concerns for continued enrollment.
•
According to interviews of emergency room physicians, less-selective
injectable
beta
agonists
such
as
epinephrine
and
terbutaline
are
not
commonly used to treat acute asthma.
The main reason they are not used
more often is due to safety concerns, particularly cardiovascular side
effects.
MN-221 Safety Review
34
©
MediciNova, Inc. 2012 |
 Safety Data:
MN-221-CL-006 Mean Heart Rate -
Change from Baseline
35
* All patients received Standard of Care including inhaled
albuterol, inhaled ipratropium, and steroids.
Note: Baseline heart rate: 90 bpm for placebo, 95 bpm for 240µg, 103 bpm
for 450µg, and 119 bpm for 1000-1080 µg Source: Draft Clinical
Study Report No. MN-221-CL-006 ©
MediciNova, Inc. 2012 |
 ©
MediciNova, Inc. 2012
36
Human
-Adrenergic Receptor
Selectivity
Test Drug
1
IC
50
(M)
2
IC
50
(M)
2
-Adrenoceptor Selectivity
(IC
50
for
1
/ IC
50
for
2
)
Levalbuterol
7.40E-06
1.40E-06
5.3
Albuterol
9.40E-06
1.60E-06
5.9
Terbutaline
6.00E-05
6.50E-06
9.2
MN-221
5.90E-06
1.40E-07
42.4 |
 ©
MediciNova, Inc. 2012
•
MN-221-CL-004:
Evaluation
of
MN-221
(bedoradrine),
a
Novel,
Highly
Selective
Beta2-Adrenergic
Receptor Agonist in Mild to Moderate Asthma via Intravenous Infusion (Poster
#145) •
MN-221-CL-005:
Comparison
of
Administration
Rates
of
MN-221
(bedoradrine),
a
Novel,
Highly
Selective Beta2 Receptor Agonist in Patients with Stable Moderate to Severe Asthma
(Poster #143) •
MN-221-CL-006:
Reduced
Hospital
Admission
and
Improved
Pulmonary
Function
Following
Intravenous MN-221 (bedoradrine), a Novel Highly Selective Beta2-Adrenergic
Receptor Agonist, Adjunctive to Standard of Care in Severe Acute Exacerbation
of Asthma (Poster #144) •
Pharmacokinetic (PK) and Pharmacodynamic (PD)
Modeling
and
Simulation
Support
the
Novelty
of
MN-221, a Highly-Selective Beta2-Adrenergic Agonist for Treatment of Acute
Asthma (Poster #146) •
MN-221 FY08-065:
Cardiovascular
Effects
of
i.v.
MN-221
(bedoradrine)
Administered
with
Nebulized
Albuterol in Dogs (Poster #147)
•
Pharmacokinetics and Pharmacodynamics of MN-221,
a Novel
Highly-Selective
Beta2-Adrenergic
Agonist for Treatment of Acute Chronic Obstructive Pulmonary Disease (Poster
#685) •
MN-221-CL-010:
Intravenous
MN-221,
a
Novel,
Highly
Selective
Beta2
Adrenergic
Receptor
Agonist,
Improves Lung Function in Stable Moderate to Severe Chronic Obstructive Pulmonary
Disease (COPD) Patients (Poster #686)
*Posters available on MediciNova website at
www.medicinova.com MN-221: CHEST Posters (Nov.
2010)* 37 |
 Ibudilast
(MN-166/AV411): Data from Completed Trials
Multiple Sclerosis Program
Neuropathic Pain Program
Drug Abuse/Addiction Program
Safety Review |
 ©
MediciNova, Inc. 2012
Placebo-controlled, Randomized, Double-blind Phase II Study:
•
Year 1 -
Placebo, 30 mg/day, 60mg/day
•
Year 2 -
30 mg/day, 60mg/day
•
297 patients (~100 patients/group) @ 25 sites in Serbia, Ukraine, Belarus,
Bulgaria and Romania
Key Inclusion Criteria:
•
Males or females aged 18 to 55 years, with relapsing remitting (RR) and/or
secondary progressive (SP) Multiple Sclerosis with continued relapses;
•
One MRI scan taken two weeks prior to treatment start using a standardized MRI
protocol with at least one Gd-enhancing lesion;
•
An Expanded Disability Status Scale (EDSS) score of 5.5 or less at the screening
and baseline visits.
Safety Profile:
•
89% (264 of 297) of subjects completed the first 12 months of the study
•
82.5% (245 of 297) of subjects completed the full 24 months of the study
•
Adverse effects reported more frequently in MN-166-treated than
placebo-treated subjects: GI effects & depression
Multiple Sclerosis Clinical Study:
Multiple Sclerosis Clinical Study:
MN-166-CL-001
MN-166-CL-001
39 |
 40
P-Value:
0.04
P-Value: 0.035
MN-166-CL-001 Study Results
P-Value:
0.026
P-Value: 0.004
P-Value: 0.09
P-Value: 0.08
Note: P-values listed on this slide compare placebo group to 60mg/day
group of MN-166 Indicative of Potential Neuroprotective Effect:
•
Reduced brain volume loss
•
Reduced conversion of acute lesions to persistent black holes
•
Sustained disability progression was significantly less likely (~50%)
Acute Clinical Benefit:
•
Prolong time to relapse (by 127 days.)
•
Annualized relapse rate
Protocol-Defined Primary Endpoint (Surrogate Endpoint):
•
No significant reduction in the cumulative number of active (gadolinium-enhancing
(T1) and non-enhancing new/enlarging (T2)) lesions on cranial MRI scans
over 12 months of treatment was observed
•
Positive trends were observed in volume of
gadolinium-enhancing (T1) lesions
©
MediciNova, Inc. 2012 |
 41
MN-166-CL-001:
Efficacy Review (One Year)
Endpoints Indicative of Disease Modifying Effect (Chronic aspects of MS):
Endpoints Relating to Acute Clinical Benefit:
Brain Volume Loss
Progression to PBH
EDSS progression
0
0.4
0.8
1.2
1.6
2
0
20
40
60
80
100
Dose (mg/d)
0
0.1
0.2
0.3
0.4
0
20
40
60
80
100
Dose (mg/d)
0
2
4
6
8
10
0
20
40
60
80
100
Dose (mg/d)
0
20
40
60
80
100
Dose (mg/d)
Time to 1st Relapse
20
30
40
50
60
70
80
90
0
20
40
60
80
100
Dose (mg/d)
% Relapse Free After One Year
:
Statistically
significant
0
100
200
300
400
500
600
700
©
MediciNova, Inc. 2012 |
 ©
MediciNova, Inc. 2012
42
Secondary Progressive MS –
Subset Analysis
Treatment Group (patient n)
Subset of
MS Patients:
Placebo
30 mg/day
Low Dose Group
60 mg/day
High Dose Group
% Brain
Volume
Change
% Brain
Volume
Change
Magnitude of
Effect
% Brain
Volume
Change
Magnitude of
Effect
RRMS
-1.2 (81)
-1.1 (69)
8% less
-0.8 (75)
33% less
SPMS
-1.0 (3)
-0.7 (4)
30% less
-0.4 (2)
60% less
Next Steps for Progressive MS:
Two-year Phase 2 in Progressive MS - month 12 data. Potential
first-in-class, once- or twice-daily oral well-tolerated
drugs with established endpoints. Draft protocols, costs, and trial operations
completed.
|
 ©
MediciNova, Inc. 2012
43
Diabetic Peripheral Neuropathic
Pain Study: AV411-010
Design: Two-center (Australian), Phase 1b/2a, randomized, double-blind,
placebo-controlled, parallel-group study.
Subjects:
•
Patients, aged 18 to 75
years, with painful diabetic peripheral neuropathy (DPN) or complex
regional pain syndrome (CRPS) of
6 months duration and screening VAS score
4
cm on a
10 cm scale
•
29 subjects: 19 active, 10 placebo
Dosing:
•
20 mg BID (n=4), 20 mg TID (n=4), 40 mg BID (n=11)
•
AV411 added
to patients’
standard medication regimen for DM and pain
Study objectives:
•
Establish safety/tolerability & PK in intended patient population
•
Explore potential efficacy endpoints |
 ©
MediciNova, Inc. 2012
Reduction Observed in Opioid Usage
44 |
 ©
MediciNova, Inc. 2012
45
Greater % of “Responders”
Above
Ibudilast Plasma Thresholds
Plasma Ibudilast Parameter
VAS ‘Responder’
%
AUC
0-24h
> 1000 ng*hr/mL
60%
< 1000 ng*hr/mL
25%
C
max
> 60 ng/mL
64%
< 60 ng/mL
14%
C
min
> 27 ng/mL
55%
< 27 ng/mL
29%
Next Steps for Neuropathic Pain:
Twelve
week
Phase
2
DPN
trial.
Potential
first-in-class,
once-
or
twice-daily
oral
well-tolerated
drug with established endpoints. Draft protocols, costs and trial operations
completed. |
 ©
MediciNova, Inc. 2012
•
Recent validation of CNS action in opioid withdrawal & analgesia
•
Ongoing Methamphetamine interaction Phase 1b
•
Opioid self-administration Phase 2a initiating
•
Ongoing Phase 2a Medication Overuse Headache Pain trial
•
Randomized, double-blind, placebo-controlled, investigator-initiated (Dr.
Pail Rolan at Univ. of Adelaide, Australia; reduced headache index, acute
medication (codeine) use and headache impact on Quality of Life (QOL);
8-week trial + follow-up; n = 20 patients each at placebo vs. 80 mg/day
of MN-166 •
Acquired rights to treatment of
post-traumatic brain injury (TBI)
•
Led by the research of Daniel Barth, Ph.D., Professor of Neuroscience and
Psychology at CU-Boulder, ibudilast demonstrated significant efficacy in a model
of post-TBI anxiety, one of the most common disorders caused by TBI.
Investigator-Led Development
46 |
 Ibudilast
- References
47
©
MediciNova, Inc. 2012 |