axs-07 and the acute treatment of migraine
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NASDAQ: AXSM
AXS-07 and the Acute Treatment of Migraine
R&D Day Conference Call
November 25, 2019
© Axsome Therapeutics, Inc.
Certain information contained in this presentation may include “forward-looking statements” within the meaning of the Private
Securities Litigation Reform Act of 1995. We may, in some cases, use terms such as “predicts,” “believes,” “potential,”
“continue,” “estimates,” “anticipates,” “expects,” “plans,” “intends,” “may,” “could,” “might,” “will,” “should” or other words that
convey uncertainty of future events or outcomes to identify these forward-looking statements. In particular, the Company’s
statements regarding trends and potential future results are examples of such forward-looking statements. The forward-
looking statements include risks and uncertainties, including, but not limited to, the success, timing and cost of our ongoing
clinical trials and anticipated clinical trials for our current product candidates, including statements regarding the timing of
initiation and completion of the trials, interim analyses and receipt of interim results; the timing of and our ability to obtain and
maintain U.S. Food and Drug Administration or other regulatory authority approval of, or other action with respect to, our
product candidates; the Company’s ability to obtain additional capital necessary to fund its operations; the Company’s ability
to generate revenues in the future; the Company’s ability to successfully defend its intellectual property or obtain the
necessary licenses at a cost acceptable to the Company, if at all; the successful implementation of the Company’s research
and development programs; the enforceability of the Company’s license agreements; the acceptance by the market of the
Company’s product candidates, if approved; and other factors, including general economic conditions and regulatory
developments, not within the Company’s control. These factors could cause actual results and developments to be materially
different from those expressed in or implied by such statements. Forward-looking statements are not guarantees of future
performance, and actual results may differ materially from those projected. The forward-looking statements are made only as
of the date of this presentation and the Company undertakes no obligation to publicly update such forward-looking statements
to reflect subsequent events or circumstance.
This presentation also contains estimates and other statistical data made by independent parties and by us relating to market
size and other data about our industry. This data involves a number of assumptions and limitations, and you are cautioned not
to give undue weight to such estimates. Neither we nor any other person makes any representation as to the accuracy or
completeness of such data or undertakes any obligation to update such data after the date of this presentation. In addition,
these projections, assumptions and estimates are necessarily subject to a high degree of uncertainty and risk.
2
Forward-Looking Statements & Safe Harbor
© Axsome Therapeutics, Inc.
FLS
3
AXS-07 andUnmet Needs in the Acute Treatment of Migraine
© Axsome Therapeutics, Inc.
Overview
Topic Discussant
Introductions Mark JacobsonSENIOR VICE PRESIDENT, OPERATIONS
Welcome Herriot Tabuteau, MDCHIEF EXECUTIVE OFFICER
Migraine: Multiple Mechanisms of Disease, Treatment Targets and the Potential for AXS-07
Stewart J. Tepper, MDPROFESSOR OF NEUROLOGY,GEISEL SCHOOL OF MEDICINEAT DARTMOUTH UNIVERSITY
Inadequate Response to Acute Migraine TreatmentRichard B. Lipton, MDPROFESSOR OF NEUROLOGYPAST PRESIDENT OF THE AMERICAN HEADACHE SOCIETY
Update on the Clinical Development of AXS-07Cedric O’Gorman, MDSENIOR VICE PRESIDENT,CLINICAL DEVELOPMENT & MEDICAL AFFAIRS
MINDSET Physician Survey Informs Market Opportunity Dave MarekCHIEF COMMERCIAL OFFICER
Panel Discussion and General Q&A Presenters
Welcome
4© Axsome Therapeutics, Inc.
Herriot Tabuteau, MD
CHIEF EXECUTIVE OFFICERAXSOME THERAPEUTICS, INC.
Migraine: Multiple Mechanisms of Disease, Treatment Targetsand the Potential for AXS-07
5© Axsome Therapeutics, Inc.
Stewart J. Tepper, MD
PROFESSOR OF NEUROLOGYGEISEL SCHOOL OF MEDICINE AT DARTMOUTH
• The World Health Organization classifies severe migraine attacks as among the most
disabling illnesses, comparable to dementia, quadriplegia and active psychosis1,2
• Debilitating pain, and the often constant fear of the next migraine attack, damage family
life, social life and employment3
• Depression and anxiety are twice as common in people with migraine than in healthy
individuals4
• Widespread misperception of the seriousness of migraine contributes to its under-
recognition and under-treatment3
• More than 70% of patients are not fully satisfied with their current treatment5
6
Migraine:Disabling Disease in Need of New Treatments
© Axsome Therapeutics, Inc.
AXS-07
There is an urgent need for new treatments that provideimproved efficacy for this serious neurological disease
1Menken et al. Arch Neurol. 2000;57:418-420.2Shapiro and Goadsby. Cephalalgia. 2007;27:991-4.3Global Burden of Disease Study. Lancet. 2017;390:1211-12594Antonaci et al. J Headache Pain. 2011;12:115–125. 5Lipton and Stewart. Headache. 1999;39(suppl 2):S20-S26.
• Emerging therapies are expected to increase treatment options for migraine sufferers:
– Anti-CGRP antibodies for prevention
– AXS-07 for acute treatment
– Oral anti-CGRPs (gepants) and lasmiditan for acute treatment
• Anti-CGRP antibodies for prevention:
– May increase the addressable market for acute treatments by increasing disease
awareness, and leading patients to seek therapy
– Most appropriate for chronic migraine (about 10% of patients)
– Reduction of about 2 migraine days per month compared to placebo
7
Migraine:Emerging Treatment Landscape
© Axsome Therapeutics, Inc.
AXS-07
100% of migraine patients, including those on preventive therapy, need acute treatment
9© Axsome Therapeutics, Inc.
AXS-07
• AXS-07 is a novel, oral, investigational medicine consisting of MoSEIC™
meloxicam and rizatriptan under development for the acute treatment of migraine
• Meloxicam is a COX-2 preferential non-steroidal anti-inflammatory drug
• Rizatriptan is a 5-HT1B/1D agonist
• AXS-07 is designed to provide rapid absorption, enhanced and consistent relief
of migraine, and reduced symptom recurrence
AXS-07 (MoSEIC™ Meloxicam/Rizatriptan) Multi-Mechanistic Treatment for Migraine
AXS-07
Migraine Process Mechanism / Action Component
CGRP Mediated✓ Inhibition of CGRP release
✓Reversal of CGRP-mediated vasodilationRizatriptan
Neuroinflammation✓Cyclooxygenase inhibition
✓PGE2 synthesis inhibition
MoSEIC™
meloxicam
Pain Signal Transmission✓Decrease passage of pain signals
to trigeminal nucleus caudalis Rizatriptan
Central Sensitization ✓Reversal of central sensitizationMoSEIC™
meloxicam
10
AXS-07 (MoSEIC™ Meloxicam/Rizatriptan) Multi-Mechanistic Treatment for Migraine
© Axsome Therapeutics, Inc.
AXS-07
Mechanisms of AXS-07 address multiple disorderedphysiological processes observed during migraine attacks
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AXS-07 (MoSEIC™ Meloxicam/Rizatriptan) Pharmacokinetic Profile – Phase 1 Results
© Axsome Therapeutics, Inc.
AXS-07
• Therapeutic AXS-07 MoSEIC™ meloxicam concentrations reached in 17 minutes
• Maximum concentrations of AXS-07 rizatriptan reached in 38 minutes
• MoSEIC™ meloxicam terminal half-life of 18.2 hours
O’Gorman C et al. Presented at the 19th Congress of the International Headache Society, 5-8 September 2019, Dublin, Ireland.
Mean Meloxicam Concentrations Mean Rizatriptan Concentrations
AXS-07 (20 mg meloxicam/10 mg rizatriptan)
Mobic® (15 mg meloxicam)
AXS-07 (20 mg meloxicam/10 mg rizatriptan)
Maxalt® (10 mg rizatriptan)
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Temporal Alignment: AXS-07 PK versus CGRP and PGE2 Increases
© Axsome Therapeutics, Inc.
AXS-07
Sarchielli et al. Cephalalgia. 2000;20:907-18.
Abbreviations: CGRP, Calcitonin gene-related peptide; PGE2, Prostaglandin E2.
Time (hrs)
Me
an
Mo
SE
IC™
me
loxic
am
co
nce
ntra
tion
(ng
/mL
)M
ea
n r
iza
trip
tan c
on
ce
ntr
atio
n (
pg
/mL
)
CGRP PGE2
CGRP (mean peak 76.7 pmol/L)
Peaks at 1 hr; decreases over 6 hrs
PGE2 (mean peak 6.38-6.62 pmol/L)
Peaks at 2 hrs; maintained through 6 hrs
• Migraine is a highly disabling neurological disease, characterized by debilitating pain, that
damages family life, social life and employment
• There is an urgent need for new treatments that provide improved efficacy for this serious
neurological disease
• Physiological changes during a migraine attack include CGRP-mediated vasodilation, and
neuroinflammation leading to initiation and maintenance of pain; and central sensitization
(allodynia) contributing to difficult-to-treat pain
• The mechanisms of AXS-07 address the multiple disordered physiological processes
observed during migraine attacks
• AXS-07 is rapidly absorbed resulting in a PK profile which aligns temporally with the
increases in CGRP and inflammatory markers observed during migraine attacks
• The multiple mechanisms of action of AXS-07 combined with a favorable PK profile may
result in improved efficacy in the acute treatment of migraine
13
Migraine: Summary
© Axsome Therapeutics, Inc.
AXS-07
Inadequate Response toAcute Migraine Treatment
14© Axsome Therapeutics, Inc.
Richard B. Lipton, MD
PROFESSOR OF NEUROLOGYPAST PRESIDENT OF THE AMERICAN HEADACHE SOCIETY
• New acute treatments for migraine must address unmet needs
• Unmet needs for efficacy can be measured using the Migraine Treatment Optimization
Questionnaire (mTOQ)
• Unmet needs are consequential
• Combining a fast-acting NSAID and a fast-acting triptan is a rational approach for
addressing unmet efficacy needs
• The MOMENTUM study enrolls patients with a history of inadequate response to their
prior acute treatments, assessed using the mTOQ-4
15
Overview
© Axsome Therapeutics, Inc.
AXS-07
• The mTOQ-4 is a patient-reported
outcome (PRO) developed to:
– Identify patients with an inadequate
treatment response
– Identify patients who require a change
of their current acute treatment
16
Determining Success with Acute Treatments: Migraine
Treatment Optimization Questionnaire (mTOQ-4)
© Axsome Therapeutics, Inc.
AXS-07
Lipton et al. Neurology. 2015;84:688-95.
• The mTOQ-4 is a patient-reported
outcome (PRO) developed to:
– Identify patients with an inadequate
treatment response
– Identify patients who require a change
of their current acute treatment
17
Determining Success with Acute Treatments: Migraine
Treatment Optimization Questionnaire (mTOQ-4)
© Axsome Therapeutics, Inc.
AXS-07
Lipton et al. Neurology. 2015;84:688-95.
IMPACTAfter taking your medication, do you feel in control enough to feel no disruption to daily activities?
GLOBAL ASSESSMENTAfter taking your medication, are you pain free within 2 hours of most attacks?
EMOTIONAL RESPONSEAre you comfortable enough with your medication to be able to plan daily activities?
CONSISTENCY OF RESPONSEDoes one dose of medication relieve your headache and keep it away for at least 24 hours?
American Migraine Prevalence and Prevention Study (AMPP)
• 8,233 respondents with episodic migraine
• 56.0% reported Inadequate 2-hour Pain Freedom response to usual acute treatment
• 53.7% reported Inadequate 24-hour Pain Relief
• Of those who achieved Adequate 2-hour Pain Freedom, 25.7% reported
Inadequate 24-hour Sustained Pain Relief or recurrence
18
Inadequate Response to Acute Migraine Treatments
AMPP Study
© Axsome Therapeutics, Inc.
AXS-07
Lipton RB et al. Headache. 2016 Nov;56(10):1635-1648.
56.0%53.7%
44.0%
0%
10%
20%
30%
40%
50%
60%
Inadequate 2 hour Pain Freedom Inadequate 24 hour Pain Relief Adequate 2 hour Pain Freedom
Pro
po
rtio
n o
f p
atie
nts
25.7%
had Inadequate
Sustained Pain
Relief
19
Inadequate Response to Acute Treatment is Consequential
© Axsome Therapeutics, Inc.
AXS-07
Progression from Episodic to Chronic Migraine by Acute Treatment Efficacy Category
6.8%
4.4%
2.7%
1.9%
0%
1%
2%
3%
4%
5%
6%
7%
8%
Very poor Poor Moderate Maximum
% P
rog
res
sin
g f
rom
EM
to
CM
8
7
6
5
4
3
2
1
0
Abbreviations: OR: Odds Ratio; CI: Confidence Index; EM: Episodic Migraine; CM: Chronic Migraine.1American Migraine Prevalence and Prevention (AMPP) Study. Lipton et al. Neurology. 2015;84:688-95.
OR = 2.55; 95% Cl 1.42–4.61
OR = 1.69; 95% Cl 1.02–2.81
OR = 1.26; 95% Cl 0.81–1.97
Degree of Treatment Optimization
Total N of group 369 1,007 2,657 1,648
Inadequate initial treatment of episodic migraine can lead to chronic migraine
Strongest predictors of Inadequate Response, based on 2-hour pain freedom,
ranked in order of strength of association:
20
Strongest Predictors of Inadequate Response AMPP Study
© Axsome Therapeutics, Inc.
AXS-07
Greater Pain Intensity
Presence of Cutaneous Allodynia
Meeting criteria for Depression
Higher body mass index
Higher average monthly headache day frequency
Lipton RB et al. Headache. 2016 Nov;56(10):1635-1648.
21
Allodynia and Inadequate ResponseAMPP Study
© Axsome Therapeutics, Inc.
AXS-07
Inadequate 24-hour Pain Response by Drug Class and Allodynia Status
Allodynia was associated with inadequate outcomesfor all medication groups (n=5,236)1
1American Migraine Prevalence and Prevention (AMPP) Study. Lipton et al. Headache. 2017;57:1026-1040.
40.7
64.268.3
57.9
29.5
50.053.4
43.7
0
10
20
30
40
50
60
70
Triptans NSAIDs Opioids Barbituates
Allodynia No Allodynia
Pe
rce
nta
ge
P<0.001
P<0.001 P<0.001
P<0.001
• MOMENTUM is enrolling only patients with a history of inadequate response to their prior
acute treatments, assessed using the mTOQ-4:
– Targets patient population at greatest clinical need
– To date majority of patients screened also exhibit cutaneous allodynia
– Enriches for population of patients with difficult-to-treat migraine
• The multiple mechanisms of AXS-07 may address the two strongest predictors of inadequate
treatment response:
– Higher pain intensity: AXS-07’s multiple mechanisms may synergize to enhance pain relief
– Cutaneous allodynia: The MoSEIC™ meloxicam component of AXS-07 may reverse
central sensitization which manifests clinically as allodynia
22
Implications for AXS-07 MOMENTUM Phase 3 TrialEvaluating Patients with Inadequate Response
© Axsome Therapeutics, Inc.
AXS-07
• MOMENTUM incorporates active comparator rizatriptan:
– Rizatriptan is considered one of the most effective and fastest acting acute migraine
therapies
– Comparative efficacy data with AXS-07 vs. rizatriptan will be generated
23
Implications for AXS-07 MOMENTUM Phase 3 TrialEvaluating Patients with Inadequate Response
© Axsome Therapeutics, Inc.
AXS-07
• New acute treatments for migraine must address unmet needs, and unmet needs for
efficacy can be measured using the mTOQ-4
• Ineffective acute treatment results in medication overuse, chronification of migraine and
poor long-term outcomes
• More than half of migraine patients report inadequate response to their usual acute
migraine treatment
• AXS-07, by combining a fast-acting NSAID and a fast-acting triptan, may address the two
strongest predictors of inadequate treatment response, which are greater pain intensity and
the presence of cutaneous allodynia
• By enrolling only patients with a history of inadequate response, the MOMENTUM study is
targeting the population where AXS-07 may have the greatest clinical utility
• Inclusion of the active comparator rizatriptan in the MOMENTUM study will generate
important comparative data
24
Summary
© Axsome Therapeutics, Inc.
AXS-07
Update on theClinical Developmentof AXS-07
25© Axsome Therapeutics, Inc.
Cedric O’Gorman MD, MBA
SENIOR VICE PRESIDENT,CLINICAL DEVELOPMENT & MEDICAL AFFAIRSAXSOME THERAPEUTICS, INC.
Patient Population
• Adult subjects with established diagnosis of migraine with or without aura
• History of inadequate response as assessed by the mTOQ-4
Co-Primary Endpoints (AXS-07 vs placebo)
• Pain Freedom at 2 hours
• Freedom from MBS at 2 hours
Key Secondary Endpoint (AXS-07 vs rizatriptan and MoSEIC™ meloxicam)
• Superiority of AXS-07 to individual components (component contribution) based on
sustained pain freedom 2-24 hours after dosing
26
MOMENTUM Study of AXS-07For the Acute Treatment of Migraine
© Axsome Therapeutics, Inc.
AXS-07
MOMENTUM: Maximizing OutcoMEs iN Treating acUte MigrainePhase 3 study of AXS-07 for the acute treatment of migraine in adults
with history of inadequate response to prior treatment
2:2:2:1
randomization
Single dose, following a qualifying migraineScreening
Rizatriptan
AXS-07
MoSEIC™ meloxicam
Placebo
✓ Study being conducted
pursuant to FDA Special
Protocol Assessment (SPA)
✓ MOMENTUM study is fully
enrolled
✓ On track to report topline
results: Q4’19
n=875
Abbreviations: MBS, most bothersome migraine-associated symptom; mTOQ-4, Migraine Treatment Optimization Questionnaire.
27
INTERCEPT Study of AXS-07For the Acute Treatment of Migraine
© Axsome Therapeutics, Inc.
AXS-07
INTERCEPT: INiTiating EaRly Control of MigrainE Pain & Associated SympToms
Phase 3 trial of AXS-07 for the acute treatment of migraine
1:1
randomization
Single dose, immediately following migraine pain onsetScreening
Placebo
AXS-07n=300
Patient Population
• Adult subjects with an established diagnosis of migraine with or without aura
• Will initiate treatment at the first sign of migraine pain onset
Co-Primary Endpoints (AXS-07 vs placebo)
• Pain Freedom at 2 hours
• Freedom from MBS at 2 hours
Abbreviations: MBS, most bothersome migraine-associated symptom.
✓ On track to report
topline results: Q1’20
MINDSET Physician Survey Informs Market Opportunity
28© Axsome Therapeutics, Inc.
Dave Marek
CHIEF COMMERCIAL OFFICERAXSOME THERAPEUTICS, INC.
42%Neurologists,HA Specialists
35%Neurologists,
Other
24%Primary Care Physicians
Primary Survey Objectives
• Understand physicians’ views of the unmet
needs in the acute treatment of migraine
• Understand physicians’ receptivity to the
potential AXS-07 product profile
29
Migraine Treatment Needs and Physician Receptivity (MINDSET) Survey
© Axsome Therapeutics, Inc.
AXS-07
Physicians Surveyed (N=106)1
Treat >50,000 migraine patients annually
1Defined as personally treating at least 100 patients with migraine at least once per year.
The MINDSET Survey was commissioned by Axsome Therapeutics and conducted by MEDACorp® in October 2019
42%
34%
21%
3% 1%
30
The Survey Highlighted Physicians’ Concerns for Patients with Difficult-to-Treat Migraine Attacks
© Axsome Therapeutics, Inc.
AXS-07
Half of patients with difficult-to-treat migraines have a history of inadequate response to prior acute migraine treatments
Three-quarters of physicians are significantly-to-moderately concerned about patients progressing to chronic migraine if they have a suboptimal response to one or more acute therapies
31%of patients have difficult-to-treatmigraine attacks
Source: MINDSET Survey conducted by MEDACorp® with Neurologists and Primary Care Physicians in October 2019; n=106.
50
39
24 2320 19
0
25
50
1
History of inadequateresponse to migrainetreatment(s)
Pain intensity (severe)
Inability to toleratecurrent treatment(s)
Migraine associatedwith allodynia
Menstrual-associatedmigraine
Morning migraine ormigraine upon awakening
Significantly concerned
Moderately concerned
Somewhat concerned
Slightly concerned
Not at all concerned
Pe
rcen
tage o
f D
ifficult-t
o-T
reat
Pa
tie
nts
(%
)
Characteristics of Difficult-to-TreatMigraine Patients
Percentage of Physicians Concerned about Progression to Chronic Migraine
31
The Survey Strongly Confirmed the Greatest Unmet Need in Migraine Remains Efficacy
© Axsome Therapeutics, Inc.
AXS-07
Patients switch acute treatments predominantly due to efficacy
Physicians believe, overwhelmingly, efficacy is the most significant unmet need in the acute treatment of migraine
Source: MINDSET Survey conducted by MEDACorp® with Neurologists and Primary Care Physicians in October 2019; n=106.
62
26
108
0
25
50
75
1
Efficacy
Tolerability
Mode of administration
Safety
Efficacy
Tolerability
Mode of administration
Safety
Pe
rcen
tage o
f P
atie
nts
(%
)
Reasons for Switching
Most Significant Unmet Need in Migraine
85%
7% 3%
1%
16%
40%
35%
7%
1% 2%
18%
38%
31%
8%
4%
2%
32
Physician Receptivity to AXS-07Potential Product Profile
© Axsome Therapeutics, Inc.
AXS-07
87%
Prescribe AXS-07
over currently available treatmentsPrescribe AXS-07
over drugs in development1
91%
Physicians’ likelihood to prescribe AXS-07 if it is shown to be superior to rizatriptan on 2-24hr sustained pain freedom in a difficult-to-treat population
with a history of inadequate response to prior acute migraine treatments:
1Including oral CGRPs.
Source: MINDSET Survey conducted by MEDACorp® with Neurologists and Primary Care Physicians in October 2019; n=106.
Significantly greater
Moderately greater
Slightly greater
Same
Slightly less
Significantly less
Percentage of Physicians
33
Physician Receptivity to AXS-07Informs Product Positioning
© Axsome Therapeutics, Inc.
AXS-07
Physicians’ likelihood to prescribe AXS-07 if shown to be superior to the current standard of care on 2-24 hour sustained pain freedom in a difficult-to-treat
population, with a similar safety profile, and no additional access/payer barriers
*Including oral CGRPs.
Source: MINDSET Survey conducted by MEDACorp® with Neurologists and Primary Care Physicians in October 2019; n=106.
Percent of patients to whom physicians would prescribe AXS-07
Initial target patient population
22
35
41
49
0
25
50
Category 1 Category 2 Category 3 Category 4
Pe
rcen
tage o
f P
atie
nts
(%
)
Treatment naive
1 priorfailure
2 priorfailures
3 or more prior failures
• Migraine-treating physicians have a significant percentage of their patients who have
difficult-to-treat migraine
• Physicians are highly concerned about difficult-to-treat migraine patients advancing to
chronic migraine
• Improved efficacy remains the greatest unmet need in the acute treatment of migraine
• If AXS-07 achieves superiority vs. rizatriptan in the MOMENTUM trial, approximately
9 out of 10 physicians would prescribe it more often than current standard-of-care and
more than other emerging therapies without demonstrating similar superiority
• AXS-07 target population expected to be patients with prior suboptimal response to
acute therapy
34
MINDSET Survey: Summary
© Axsome Therapeutics, Inc.
AXS-07
35
Q&A
© Axsome Therapeutics, Inc.
Closing Remarks
36© Axsome Therapeutics, Inc.
Herriot Tabuteau, MD
CHIEF EXECUTIVE OFFICERAXSOME THERAPEUTICS, INC.
axsome.com
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