Potential to Transform the Treatment Paradigm for Migraine Prevention - August 2019
←
→
Page content transcription
If your browser does not render page correctly, please read the page content below
June 14, 2018
Potential to Transform the Treatment
Paradigm for Migraine Prevention
August 2019
Investor Presentation
Forward-Looking Statements
This presentation and the accompanying commentary contains certain forward-looking statements within the
meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities
Exchange Act of 1934, as amended. Forward-looking statements include all statements that are not historical
facts and typically contain words such as “believe,” “will,” “may,” “estimate,” “continue,” “anticipate,” “intend,”
“should,” “plan,” “approximately,” “expect,” “predict,” “could,” “support,” “potential,” “opportunity,” “positive,”
“significant,” “unique,” “strong,” “unmet,” “need,” “design,” “strategy,” “advance,” “options,” “robust,” “path,”
“milestones,” “upcoming,” “enable,” “ensure,” “maintain,” “achieve,” “sufficient,” “projected,” “forecasted,”
“new,” “sets,” “establishes,” “on track,” “freedom” or the negative of these terms or other similar expressions.
You should consider forward-looking statements carefully because they discuss future expectations, contain
projections of future results of operations or financial condition, or state other “forward-looking” information.
These statements relate to our possible and future results of operations, financial condition, business
strategies, development plans, regulatory activities, competitive position, commercial plans, potential growth
opportunities and effects of competition and the assumptions that underlie these statements. These forward-
looking statements are subject to certain risks and uncertainties that could cause actual results to differ
materially from those anticipated in the forward-looking statements. Factors that might cause such a
difference include, but are not limited to, the risks outlined under the caption “Risk Factors” set forth in Alder’s
Quarterly Report on Form 10-Q for the quarter ended June 30, 2019, which was filed with the Securities and
Exchange Commission (SEC) on August 6, 2019 and is available on the SEC’s website at www.sec.gov, and
in other reports and filings we will make with the SEC from time to time. Forward-looking statements are
based on our management’s beliefs and assumptions and on information currently available to our
management. These statements, like all statements in this presentation, speak only as of the date of this
presentation (or an earlier date, where specifically noted), and except as required by law, we undertake no
obligation to update or revise these statements in light of future developments.
For investor audiences only.
2
Investor Presentation
Alder BioPharmaceuticals
Compelling Value Proposition
Potential to Transform the Treatment
Paradigm for Migraine Prevention
LARGE
EXPANSION
UNDERSERVED EPTINEZUMAB
OPPORTUNITIES
PATIENT POPULATION EPTINEZUMAB WELL POSITIONED TO
IN EPTINEZUMAB
AND MARKET DIFFERENTIATED GAIN SIGNIFICANT
ACUTE STUDY AND
OPPORTUNITY CLINICAL PROFILE MARKET SHARE
ALD1910
Investor Presentation - Eptinezumab and ALD1910 are investigational products and have not been approved by the FDA or any other regulatory body. 3
Migraine is a Serious Debilitating
Neurological Disease
Economic loss due
to migraines
Most disabling
disease during ~$36B per year2
the most
productive years Lost work days
of people’s lives1 113M per year2
9/10 people with migraine
can’t “function
Attacks usually last
normally” and 3/10
4-72 hours2 require bed rest during
Symptoms include migraine strikes3
extreme pain, nausea,
vomiting, extreme Chronic migraine often
sensitivities to light and leads to depression,
sound, gastrointestinal anxiety, and sleep
issues disturbances2
1Steiner, TJ, Stovner, LJ, & Vos, T. The Journal of Headache and Pain (2018) 19:17 .”Most disabling disease of people under 50 years old.”
2Migraine Research Foundation. Migraine Facts. Available at: https://migraineresearchfoundation.org/about-migraine/migraine-facts/. Accessed January 2, 2019.
3National Headache Foundation, AMPP Fact Sheet. Available at: https://headaches.org/2007/08/11/ampp-fact-sheet/. Accessed May 16, 2019.
Investor Presentation - Eptinezumab is an investigational product and has not been approved by the FDA or any other regulatory body. 4
Patients are Suffering & Need Preventive
Medications that Work, and Work Faster1
Migraine profoundly affects patients’ lives…
% %
34 %
63 66
Say migraine attacks have
Say migraine affects
Have lost a job due their ability to maintain affected their professional
to migraine2 relationships1 advancement1
…And patients value efficacy and speed regardless of the mode of administration
% rate effectiveness rate fast acting as an
%
87 as important in determining
whether they accept
79 important treatment feature
when considering migraine
treatment (highest-rated)1 prevention1
90 % Say “I will never give up fighting to find a solution”1
1 Alder proprietary patient market research, 2017 (N=250).
2 Chronic Migraine in America Survey Results, 2013. Presented by migraine.com.
Investor Presentation - Eptinezumab is an investigational product and has not been approved by the FDA or any other regulatory body. 5
U.S. Anti-CGRP Migraine Prevention
Market Forecasted To Be >$5 Billion1
14M patient candidates suffer from 4+ headache days per month1
only 27% receive some form of preventive treatment
Oral preventives fail to meet Up to 80% of patients discontinue
needs of many patients: use of oral preventives within 6-12
adherence, safety, tolerability
of Eligible months due to lack of efficacy
issues3 Patients on and/or tolerability4,5
Migraine
Prevention3
Newly-launched subQ anti-CGRPs: Q2’19 NBRx Share2
~383K NBRx since launch2 Aimovig 40.1%
Commoditized market with similar Ajovy 21.9%
clinical profile. Emgality 38.0%
1 DRG 2018 Migraine Market report.
2 IQVIA NPA Weekly through July 19, 2019
3 Parsekyan D. Migraine prophylaxis in adult patients. West J Med. 2000;173(5):341-345.
4 Lipton RB, Bigal ME, Diamond M, et al. Migraine prevalence, disease burden, and the need for preventive therapy. Neurology. 2007;68(5):343-349.
5 Hepp Z, Dodick DW, Varon SF, et al. Adherence to oral migraine-preventive medications among patients with chronic migraine. Cephalalgia. 2015;35(6):477-488.
Investor Presentation - Eptinezumab is an investigational product and has not been approved by the FDA or any other regulatory body. 6
Alder BioPharmaceuticals
Compelling Value Proposition
Potential to Transform the Treatment
Paradigm for Migraine Prevention
LARGE
EXPANSION
UNDERSERVED EPTINEZUMAB
OPPORTUNITIES
PATIENT POPULATION EPTINEZUMAB WELL POSITIONED TO
IN EPTINEZUMAB
AND MARKET DIFFERENTIATED GAIN SIGNIFICANT
ACUTE STUDY AND
OPPORTUNITY CLINICAL PROFILE MARKET SHARE
ALD1910
Investor Presentation - Eptinezumab and ALD1910 are investigational products and have not been approved by the FDA or any other regulatory body. 7
Eptinezumab Differentiation Designed Into the
Molecule Enabling Delivery To Meet Patient Needs
Eptinezumab mAb Quarterly 30-Minute
Infusion
Eptinezumab’s
highly
competitive
High specificity with Total administered clinical profile
potent binding affinity dose is immediately
to the ligand for rapid active to inhibit
suppression of CGRP with 100%
CGRP biology1 bioavailability1,2
1. Baker B, Schaeffler B, Cady R, et al; Rational design of a monoclonal antibody (mAb) inhibiting calcitonin gene-related peptide, ALD403 (eptinezumab), intended for the prevention of migraine. Poster presented at the American
Academy of Neurology (AAN) 2017 Annual Meeting.
2. As compared to 50% -70% for subcutaneous anti-CGRPs; Vu et.al., Pharm Res. 2017 Sep; 34(9):1784-1795; Vermeersch, et al., J Pharmacol Exp Ther 354:350–357, September 2015.
Investor Presentation - Eptinezumab is an investigational product and has not been approved by the FDA or any other regulatory body. 8Completed Pivotal Studies Demonstrate
Eptinezumab’s Unique Profile
FAST
PROMISE 1 in Episodic Migraine Patients1 onset of prevention
Day 1 post-infusion
(N=888; baseline ~9 migraine days/month)
• Met primary and key secondary endpoints
• Safety and tolerability similar to placebo POWERFUL
≥50%, ≥75% and
100% reductions in
migraine days
PROMISE 2 in Chronic Migraine Patients2
(N=1,072; baseline ~16 migraine days/month) SUSTAINED
for 3 months following
• Met primary and all key secondary endpoints
a single administration
• Safety and tolerability similar to placebo and sustained or
further increased with
subsequent infusions
1. Saper J et al. Neurology. 2018;90(suppl 15):S20. Scientific Platform Presentation by Silberstein S at the American Academy of Neurology (AAN) 2018 Annual Meeting, April 21-27, 2018; Los Angeles, CA; Silberstein, S et al. Eptinezumab Results for the
Prevention of Episodic Migraine Over 1 Year in the PROMISE-1 (PRevention Of Migraine via Intravenous eptinezumab Safety and Efficacy-1) Trial. Poster Presentation at the American Headache Society (AHS) 2018 Annual Scientific Meeting. June 28 –
July 1, 2018; San Francisco, CA.
2. Lipton R et al. A Phase 3 Study to Evaluate Eptinezumab for Preventive Treatment of Chronic Migraine: Results of PROMISE-2 (PRevention Of Migraine via Intravenous eptinezumab Safety and Efficacy-2) Trial. Poster Presentation at the American
Headache Society (AHS) 2018 Annual Meeting. June 28 – July 1, 2018; San Francisco, CA..
Investor Presentation - Eptinezumab is an investigational product and has not been approved by the FDA or any other regulatory body. 9Fast: Statistically Significant Day 1
Onset of Prevention Demonstrated
PROMISE 2: Chronic Migraine
% of Patients with Migraine, Days 1-28
60% Infusion 1
Day 1 Reduction in Migraine Prevalence
Eptinezumab, 300mg, 52% reduction+
Eptinezumab, 100mg, 50% reduction+
Patients with Migraine, %
50%
Average Daily Placebo 27% reduction
Baseline
Prevalence of
Migraine: ~58%
40%
30%
20%
Day 0 Day 1 Day 7 Day 14 Day 21 Day 28
+ statistically significant; Day 1 prevalence rate comparison between eptinezumab vs. placebo
Lipton R et al. A Phase 3 Study to Evaluate Eptinezumab for Preventive Treatment of Chronic Migraine: Results of PROMISE-2 (PRevention Of Migraine via Intravenous eptinezumab Safety and Efficacy-2) Trial. Poster Presentation at the
American Headache Society (AHS) 2018 Annual Meeting. June 28 – July 1, 2018; San Francisco, CA.
Investor Presentation - Eptinezumab is an investigational product and has not been approved by the FDA or any other regulatory body. 10Powerful and Sustained: ≥50% Responder Rate by
Month 1 and Sustained or Further Increased Efficacy
with Subsequent Infusion
PROMISE 2: Chronic Migraine
≥50% Migraine Responder Rates
Eptinezumab 100 mg Eptinezumab 300 mg Placebo
70
64.0
60.6 61.4 + 61.0
60 57.6 +
54.5
50
44.0
39.3
Patients, %*
40 36.1
30
20
10
0
INFUSION 1 INFUSION 1 INFUSION 2
Month 1 Months 1-3 Months 4-6
+ statistically significant
Lipton R et al. Eptinezumab for Prevention of Chronic Migraine: Results of 2 Quarterly Intravenous Infusions in the Phase 3 PROMISE-2 (PRevention Of Migraine via Intravenous eptinezumab Safety and
Efficacy-2) Trial. Scientific Presentation at the American Headache Society (AHS) 2018 Annual Meeting. June 28 – July 1, 2018; San Francisco, CA.
Investor Presentation - Eptinezumab is an investigational product and has not been approved by the FDA or any other regulatory body. 11Powerful and Sustained: ≥75% Responder Rate
by Month 1 and Sustained or Further Increased
Efficacy with Subsequent Infusion
PROMISE 2: Chronic Migraine
≥75% Migraine Responder Rates
Eptinezumab 100 mg Eptinezumab 300 mg Placebo
50
43.1
40
39.3
36.9 +
+
33.1 +
30.9
30
Patients, %*
26.7 +
23.8
20
15.6 15.0
10
0
INFUSION 1 INFUSION 1 INFUSION 2
Month 1 Months 1-3 Months 4-6
+ statistically significant
Lipton R et al. Eptinezumab for Prevention of Chronic Migraine: Results of 2 Quarterly Intravenous Infusions in the Phase 3 PROMISE-2 (PRevention Of Migraine via Intravenous eptinezumab Safety and
Efficacy-2) Trial. Scientific Presentation at the American Headache Society (AHS) 2018 Annual Meeting. June 28 – July 1, 2018; San Francisco, CA.
Investor Presentation - Eptinezumab is an investigational product and has not been approved by the FDA or any other regulatory body. 12Powerful and Sustained: 100% Responder Rate
14.0% (100mg) and 19.1% (300mg) of epti-treated patients
experienced no migraines for at least half of the study period (≥3
months) compared with 4.9% of those on placebo
90%
PROMISE 2: Chronic Migraine
Number of Migraine-Free Study Months*
80% Over 6 Months of Treatment
70%
Percent of Patients
60%
50%
Eptinezumab 100 mg (n=356)
40% Eptinezumab 300 mg (n=350)
Placebo (n=366)
30%
20%
10%
0%
0 ≥1 ≥2 ≥3 ≥4 ≥5 6
Number of Migraine-Free Study Months
*Defined as 28 consecutive days without migraine during a study month, with the first day of dosing used as the reference point.
Winner P. et. al., Migraine-Free Months in Patients With Episodic or Chronic Migraine Treated With Eptinezumab: Results From the PROMISE-1 and PROMISE-2 Trials. Poster Presentation at the American Headache
Society (AHS) 2019 Annual Meeting. July 11-14, 2019; Philadelphia, PA.
Investor Presentation - Eptinezumab is an investigational product and has not been approved by the FDA or any other regulatory body. 13Patient Reported Outcomes: HIT-6
Clinically Meaningful Changes as Early as Month 1
in Chronic Migraine Patients (PROMISE 2)
Baseline score:
~66.7 Dose 1 Dose 1 Dose 2
Month 1 Month 3 Month 6
0
-1
Mean Change from Baseline*
-2
-3
-4
-5
-5.1 -4.9
-6
-6.1
-7 -6.7
-7.2
-8
-7.9
-9
-8.3
-9.0
-10
-9.3
Eptinezumab 100 mg (n=223) Eptinezumab 300 mg (n=230) Placebo (n=241)
Clinically meaningful change
*Clinically meaningful change in HIT-6 total score was defined as a ≥6-point decrease.
Nagy A.J. et. al., Treatment With Eptinezumab Demonstrated Meaningful Improvements in Patients With Chronic Migraine Experiencing a High Frequency of Severe Migraines. Poster Presentation at the American
Headache Society (AHS) 2019 Annual Meeting. July 11-14, 2019; Philadelphia, PA.
14
Investor Presentation - Eptinezumab is an investigational product and has not been approved by the FDA or any other regulatory body.Safety Data – Integrated Summary of
Pivotal Studies
Adverse reactions occurring with an incidence of ≥2% for either dose of
Eptinezumab and ≥2% greater than placebo for PROMISE 1 & PROMISE 2
Eptinezumab Eptinezumab Placebo every
100 mg every 300 mg every 3 months
Adverse Reactions
3 months 3 months
N=579 N=574 N=588
Nasopharyngitis 6% 8% 6%
Source: Data on file
Investor Presentation - Eptinezumab is an investigational product and has not been approved by the FDA or any other regulatory body. 15Alder BioPharmaceuticals
Compelling Value Proposition
Potential to Transform the Treatment
Paradigm for Migraine Prevention
LARGE
EXPANSION
UNDERSERVED EPTINEZUMAB
OPPORTUNITIES
PATIENT POPULATION EPTINEZUMAB WELL POSITIONED TO
IN EPTINEZUMAB
AND MARKET DIFFERENTIATED GAIN SIGNIFICANT
ACUTE STUDY AND
OPPORTUNITY CLINICAL PROFILE MARKET SHARE
ALD1910
Investor Presentation - Eptinezumab and ALD1910 are investigational products and have not been approved by the FDA or any other regulatory body. 16Concentrated Marketplace
Top 11% or ~2,000 Accounts Prescribe 80%
of Anti-CGRP subQ Treatments
Alder To Target Top 2,000 Accounts, driving 80%1 of subQ Anti-CGRP volume
Academic, 5%
Q1’19 Rx/ Q1’19 v Q4’18
Group
80% 80%
Acct Growth
% of Business
Community,
Alder Medical 29%
150 Rx 20 Rx / acct
Targets Groups,
66%
Others 6 Rx 2 Rx / acct
20%
~2,000 •See an average of 150-200 95% 75% 70%
Headache / Pain migraine patients per month1 Have IV access Have prescribed Have prescribed
Centers, Neurology
Practices, and •Often see patients at a 70% have an IV to their Botox to their
quarterly cadence1 in-office patients patients for
Hospitals
access1 for migraine1 migraine1
Our specialty-sized
sales force will have 75-100 reps
1 IQVIA Xponent & claims data – March 2019
17
Investor Presentation - Eptinezumab is an investigational product and has not been approved by the FDA or any other regulatory body.Concentrated Marketplace
Top 3% or ~500 Accounts Prescribe 50%
of Anti-CGRP subQ Treatments
Alder Target To Include Top 500 Accounts, driving 50%1 of subQ Anti-CGRP volume
Academic,
5%
Q1’19 Rx/ Q1’19 v Q4’18
Group
80% 50%
Acct Growth
% of Business
Alder Medical Community,
346 Rx 33 Rx / acct Groups, 65% 30%
Targets
50% Others 13 Rx 3 Rx / acct
~500 •See an average of 200-300 95% 80% 83%
Headache/ Pain migraine patients per month1 Have IV access Have prescribed Have prescribed
Centers, Neurology
Practices, and •Often see patients at a 80% have an IV to their Botox to their
quarterly cadence1 in-office patients patients for
Hospitals
access1 for migraine1 migraine1
Our specialty-sized
sales force will have 75-100 reps
1 IQVIA Xponent & claims data – March 2019
18
Investor Presentation - Eptinezumab is an investigational product and has not been approved by the FDA or any other regulatory body.Market Research Suggests 83% of Neurologists and
Headache Specialists Plan to Prescribe Eptinezumab
HCP perceptions of Advantages2
Anticipated Eptinezumab
Prescribing1 Efficacy, Day 1 & Sustained Response:
• Rapid noticeable improvement is very
100% welcome; “these patients are suffering”
• Efficacy present throughout the injection
90% cycle
83% Do not plan to
80% Efficacy Response Rate ≥75%:
prescribe • In Both Episodic and Chronic
70% eptinezumab • Data perceived better than other anti-CGRPs
• Efficacy does not wear-off before next
60% quarterly IV dose
50%
IV Administration:
40% • 100% Bioavailable
• MD knows if patient complies with treatment
30% Will prescribe
eptinezumab
20%
MOA:
10% • Some speculate eptinezumab’s binding to
alpha/beta forms may yield better efficacy
0%
1RealTime Dynamix Migraine Prevention Survey Q2 2019, Spherix Global Insights.
For those patients for whom you would consider using eptinezumab, are you likely to give the infusion in your office or refer to another site of care? (n=104)
2Benefit Ladder Qualitative Research May-June 2019; Techniclarity. When assessing IV infusion, providers segment: 1) those who already administer IVs at
their practice; 2) those who have the potential to; and 3) those who can’t offer IVs because of limited space and/or staff (n=20).
Investor Presentation - Eptinezumab is an investigational product and has not been approved by the FDA or any other
19regulatory body. 19Market Research Suggests Eptinezumab
Well-Positioned for Adoption
HCP feedback on potential eptinezumab share of
~20-30% anti-CGRP market based on clinical profile2
Procedure-Oriented
Headache Specialists,
Neurologists, Pain 3 in 5 physicians believe less frequent administration and rapid onset of effect are
Specialists and PCPs1 important to prescribing migraine prevention2
% % %
52 74 64
14 MILLION would choose a quarterly believe IV medications would always choose the
PATIENTS3 IV with eptinezumab’s work the fastest when most effective option
profile over a monthly compared to other regardless of
SubQ preventive injection forms of administration method4
therapy4 administration4
1 Alder proprietary physician market research, 2017.
2 Alder proprietary ATU physician market research, 2018.
3 DRG 2018 Migraine Market report.
4 Alder proprietary patient market research, 2017 (N=250)
20
Investor Presentation - Eptinezumab is an investigational product and has not been approved by the FDA or any other regulatory body.Alder is Uniquely Positioned to
Capture High-Value Market Opportunity
Migraine is a Serious Eptinezumab’s
Debilitating Disease Differentiated ~ 2,000 accounts
Characteristics2 driving 80%
of anti-CGRP subQ Rx4
FAST
onset of prevention Day 1
post-infusion3 ~20-30% potential
eptinezumab share of anti-
CGRP prevention market5
US Anti-CGRP
✓ POWERFUL
>50%, >75% and
Migraine Prevention 100% reductions in ~ 14M
Forecasted to be a migraine days patients who are
>$5 Billion Market1 candidates for prevention
SUSTAINED Only 27% are treated 6,8
for 3 months following
a single administration and
sustained or further
52%
$ increased with subsequent of patients would choose
infusions eptinezumab over a
subcutaneous therapy7
1 6 DRG 2018 Migraine Market report.
DRG 2018 Migraine Market report
2 Eptinezumab 7 Alder proprietary patient market research, 2017 (N=250)
PROMISE 1 and PROMISE 2 studies
3 Benefit observed within the first infusion period 8 American Headache Society Position Statement. Headache 2018 0:1-18.
4 IQVIA Xponent & claims data – March 2019
5 Alder proprietary market research ATU 2018
Investor Presentation. - Eptinezumab is an investigational product and has not been approved by the FDA or any other regulatory body. 21Alder BioPharmaceuticals
Compelling Value Proposition
Potential to Transform the Treatment
Paradigm for Migraine Prevention
LARGE
EXPANSION
UNDERSERVED EPTINEZUMAB
OPPORTUNITIES
PATIENT POPULATION EPTINEZUMAB WELL POSITIONED TO
IN EPTINEZUMAB
AND MARKET DIFFERENTIATED GAIN SIGNIFICANT
ACUTE STUDY AND
OPPORTUNITY CLINICAL PROFILE MARKET SHARE
ALD1910
Investor Presentation - Eptinezumab and ALD1910 are investigational products and have not been approved by the FDA or any other regulatory body. 22Phase 3 Acute Trial
Planned to Begin 2H19
Co-Primary Endpoints
100 mg eptinezumab Measured 2 hours post-treatment
vs.
• Patients achieving freedom from pain
Placebo • Absence of most bothersome symptom
Post hoc analysis of time-to-migraine resolution in patients entering 3 prior
eptinezumab clinical trials with active migraine:
• 2-hour resolution rates observed – demonstrating clear trend
• Supported design of well-powered Phase 3 trial to detect meaningful
difference vs. placebo in acute setting
Investor Presentation - Eptinezumab is an investigational product and has not been approved by the FDA or any other regulatory body. 23Acute Trial
Potential “Treat and Prevent” Label to Drive Brand Choice
~5M chronic migraine patients1
Prevention >50% chance of having a migraine the day of a physician visit2
Market
~9M episodic migraine patients1
~1/3 have a migraine the day of a physician visit2
14M patients with 1-3 migraines per month1
Opportunity to treat their migraines acutely with preventive
benefit, further expanding market potential
FirstWord Therapy Trends indicate that a CGRP mAb with a “treat and prevent” label
would be a strong driver of brand choice3
KOLs demand treatments that are The ability to treat an acute migraine
rapid in action, capable of sustaining with effective and sustained
effect without burdensome side prevention for three months is a
effects, with the ideal treatment also paradigm shift in the treatment
preventing future attacks.3 armamentarium3
1DRG 2018 Migraine Market report.
2Based on mathematic likelihood of chronic (≥15 migraine attacks/month) and episodic (4-14 migraine attacks/month) patients presenting with headache.
3FirstWord Therapy Trends: Migraine Feb ’19
24
Investor Presentation - Eptinezumab is an investigational product and has not been approved by the FDA or any other regulatory body.ALD1910 Aims to Expand Migraine
Prevention with Anti-PACAP Antibody
PACAP inhibition offers a differentiated approach to migraine prevention
2
ALD1910
• Like CGRP, infusion of PACAP has been
shown to induce migraine attacks in migraine
patients1
• Preclinical data indicate
~75%
that
Estimated to respond well to PACAP and
CGRP may have non-redundant
eptinezumab (anti-CGRP) 2 pharmacology
with respect to migraine-associated symptoms3
5M
ALD1910 is an anti-PACAP antibody
• Highly potent and selective humanized antibody4
• Ligand approach allows inhibition of binding with multiple PACAP receptors (PAC1, VPAC1 and VPAC2)4
• GMP manufacturing and IND-enabling studies underway to enable Phase 1 initiation by the end of 2019
and subsequently support IND
1 Schytz et al., Neurotherapeutics 2010; 7(2): 191–196
2 Modified from Kaiser & Russo, Neuropeptides 2013;47(6):1-24 (Refers to multiple PACAP receptors)
3 Alder unpublished research demonstrating that PACAP-driven migraine symptoms in rodents are not inhibited by anti-CGRP antibodies
4J Pharmacol Exp Ther 369:26–36, April 2019
25
Investor Presentation - ALD1910 is an investigational product and has not been approved by the FDA or any other regulatory body.Observation Time (min)
Pre-clinical Model Supports ALD1910 Inhibits
PACAP-Driven Photophobia, but an Anti-PAC1R
Antibody Does Not1
Tx2: Ab - scatter plot mAb
Anti-PAC1R
200
Average Time in Light (sec)
Vehicle + Con Ab n=10
150
Vehicle + PAC1 Ab n=8
PACAP + Con Ab n=6 Anti-PACAP ALD1910
PACAP + PAC1 Ab n=9
100
50
0
30mgs/kg
Average Time in Light (sec)
250
Vehicle + Con Ab n=9
200 Vehicle + PAC1 Ab n=9
30mgs/kg
PACAP + Con Ab n=7
150 PACAP + PAC1 Ab n=7
100
50
0
Observation Time (min)
100mgs/kg
Differential inhibition of photophobia in a predictive
pre-clinical model for migraine symptoms in humans
1 Alder unpublished research results
26
Investor Presentation - ALD1910 is an investigational product and has not been approved by the FDA or any other regulatory body.ALD1910 Inhibits PACAP-driven Vasodilation
in Cynomolgus Monkeys
1
ALD1910 led to inhibition of PACAP-driven
vasodilation under these conditions
Pre ALD1910 Post ALD1910
Degree of Vasodilation
high
Injection site 1 – Saline Solution
Injection site 2 – PACAP
Injection site 3 – PACAP
Injection site 4 – PACAP
low
Vasodilation post PACAP challenge (no ALD1910 led to inhibition of PACAP-driven
ALD1910) vasodilation under these conditions
1 DPBS is Dulbecco’s Phosphate Buffered Saline 27
Investor Presentation - ALD1910 is an investigational product and has not been approved by the FDA or any other regulatory body.Recent Execution and Key Upcoming
Milestones
Eptinezumab Anticipated Launch
Eptinezumab PDUFA Date
ALD1910 First in Human Study Q1 2020
Eptinezumab Phase 3 Acute Study Initiation Feb. 21,
2020
2H 2019
BLA Acceptance – April 22, 2019
2H 2019
BLA Submission – Feb. 21, 2019
PK Comparability Study Data
Open Label Safety Study Data
PROMISE 2 Chronic Migraine
PROMISE 1
Data
✓ Met all key milestones to
Episodic Migraine
Data
date and on track to meet
upcoming milestones for
eptinezumab and ALD1910
in 2019 & 2020
Investor Presentation - Eptinezumab and ALD1910 are investigational products and have not been approved by the FDA or any other regulatory body. 282Q19 Financial Results
and 2019 Financial Outlook*
• 2Q19 Cash Position
‒ Cash position of $440.7M1 as of June 30, 2019
• 2019 Outlook
‒ Total 2019 cash investment2 in the range of $285M and $315M
• Sufficient cash to meet projected operating requirements through the
anticipated launch of eptinezumab and into the latter part of 2020, with
key activities including:
‒ Advancing eptinezumab’s supply chain
‒ Building commercial inventory
‒ Continued build out of Alder’s commercial footprint
(e.g., marketing, sales, medical affairs, payer access, IT)
‒ Pre-launch market readiness
1 Includes cash, cash equivalents, investments and restricted cash
2 Net cash used in operating activities plus purchases of property and equipment, as defined under U.S. Generally Accepted Accounting Principles.
*Outlook as of Aug 6, 2019
29
Investor Presentation - Eptinezumab and ALD1910 are investigational products and have not been approved by the FDA or any other regulatory body.Appendix
Investor Presentation 30Fast: Statistically Significant Day 1
Onset of Prevention Demonstrated
PROMISE 1: Episodic Migraine
% of Patients with Migraine, Days 1-28
35%
Day 1 Reduction in Migraine Prevalence
Infusion 1 Eptinezumab, 300mg, 55% reduction+
Eptinezumab, 100mg, 52% reduction+
30%
Placebo 24% reduction
Percent of Patients with Migraine
Average (28 day)
Baseline
25% Prevalence of
Migraine: ~ 30%
20%
15%
10%
Day 0 Day 1 Day 7 Day 14 Day 21 Day 28
+ Statistically significant (unadjusted)
Silberstein, S et al. Eptinezumab Results for the Prevention of Episodic Migraine Over 1 Year in the PROMISE-1 (PRevention Of Migraine via Intravenous eptinezumab Safety and Efficacy-1) Trial. Poster
Presentation at the American Headache Society (AHS) 2018 Annual Scientific Meeting. June 28 – July 1, 2018; San Francisco, CA.
Investor Presentation - Eptinezumab is an investigational product and has not been approved by the FDA or any other regulatory body. 31Powerful and Sustained: ≥50% Responder Rate by
Month 1 and Sustained or Further Increased Efficacy
with Subsequent Infusions
Baseline: ~8.6 PROMISE 1: Episodic Migraine
Migraine Days
≥50% Migraine Responder Rates
Eptinezumab 100 mg Eptinezumab 300 mg Placebo
80
69.8§
70
64.7§
59.3
60 56.3 56.3++ 55.4
49.8+
50
Patients, %*
40.5
40 37.4
30
20
10
0
INFUSION 1 INFUSION 1 INFUSION 4
Month 1 Months 1-3 Months 10-12
++ statistically significant; + statistically significant (unadjusted); §statistically significant (post-hoc)
Saper J et al. Neurology. 2018;90(suppl 15):S20. Scientific Platform Presentation by Silberstein S at the American Academy of Neurology (AAN) 2018 Annual Meeting, April 21-27, 2018; Los Angeles, CA
Silberstein, S et al. Eptinezumab Results for the Prevention of Episodic Migraine Over 1 Year in the PROMISE-1 (PRevention Of Migraine via Intravenous eptinezumab Safety and Efficacy-1) Trial. Poster
Presentation at the American Headache Society (AHS) 2018 Annual Scientific Meeting. June 28 – July 1, 2018; San Francisco, CA.
Investor Presentation - Eptinezumab is an investigational product and has not been approved by the FDA or any other regulatory body. 32Powerful and Sustained: ≥75% Responder Rate
by Month 1 and Sustained or Further Increased
Efficacy with Subsequent Infusions
Baseline: ~8.6 PROMISE 1: Episodic Migraine
Migraine Days
≥75% Migraine Responder Rates
Eptinezumab 100 mg Eptinezumab 300 mg Placebo
60
54.1§
50
39.4 39.6
40
Patients, %*
++
30.8 ++ 31.5 29.7 ++
30
22.2 NS
20.3
20
16.2
10
0
INFUSION 1 INFUSION 1 INFUSION 4
Month 1 Months 1-3 Months 10-12
++ statistically significant; §statistically significant (post-hoc); NS, not significant
Saper J et al. Neurology. 2018;90(suppl 15):S20. Scientific Platform Presentation by Silberstein S at the American Academy of Neurology (AAN) 2018 Annual Meeting, April 21-27, 2018; Los Angeles, CA
Silberstein, S et al. Eptinezumab Results for the Prevention of Episodic Migraine Over 1 Year in the PROMISE-1 (PRevention Of Migraine via Intravenous eptinezumab Safety and Efficacy-1) Trial. Poster
Presentation at the American Headache Society (AHS) 2018 Annual Scientific Meeting. June 28 – July 1, 2018; San Francisco, CA.
Investor Presentation - Eptinezumab is an investigational product and has not been approved by the FDA or any other regulatory body. 33Powerful and Sustained: 100% Responder Rate
18.1% (100mg) and 25.2% (300mg) of epti-treated patients experienced
no migraines for at least half of the study period (≥6 months) compared
with 12.6% of those on placebo
70% PROMISE 1: Episodic Migraine
Number of Migraine-Free Study Months*
Over 12 Months of Treatment
60%
50%
Percent of Patients
40%
Eptinezumab 100 mg (n=221)
30% Eptinezumab 300 mg (n=222)
Placebo (n=222)
20%
10%
0%
0 ≥1 ≥2 ≥3 ≥4 ≥5 ≥6 ≥7 ≥8 ≥9 ≥10 ≥11 12
Number of Migraine-Free Study Months
*Defined as 28 consecutive days without migraine during a study month, with the first day of dosing used as the reference point.
Winner P. et. al., Migraine-Free Months in Patients With Episodic or Chronic Migraine Treated With Eptinezumab: Results From the PROMISE-1 and PROMISE-2 Trials. Poster Presentation at the American Headache
Society (AHS) 2019 Annual Meeting. July 11-14, 2019; Philadelphia, PA.
Investor Presentation - Eptinezumab is an investigational product and has not been approved by the FDA or any other regulatory body. 34You can also read
