Alder Reports Phase 2b Trial of ALD403 Meets Primary and Secondary Endpoints Demonstrating Migraine Prevention in Patients with Chronic Migraine 

Key Points

• The 300 mg and 100 mg dose levels of ALD403 met the primary efficacy endpoint of the study, a 75% reduction in migraine days over the entire 12 weeks in 33% and 31% of patients, respectively (p < 0.05).

*(p= < 0.05)   **(p= < 0.01)

• A single administration of ALD403 resulted in an immediate and durable mean reduction in migraine days from baseline throughout the 12 weeks at the 300 mg (p < 0.01), 100 mg (p < 0.01) and 30 mg (p < 0.05) dose levels, meeting the secondary efficacy endpoint.
• A single administration of ALD403 at 300mg, 100mg or 30mg dose levels demonstrated a durable reduction in migraine days for the entire 12 weeks, supporting a quarterly dosing strategy.
• The 10 mg dose of ALD403 was identified as sub-therapeutic.
• The safety profile was consistent with earlier ALD403 clinical trials.

Phase 1 Clinical Trial Evaluating Multiple Doses of ALD403 in Healthy Volunteers

The Phase 1 clinical trial is a placebo-controlled, randomized, multi-dose, double dummy, quarterly-dosing study comparing the intravenous, subcutaneous and intramuscular routes of administration in healthy volunteers. Sixty healthy volunteers, 12 in each group, were randomized as follows:

• 100 mg ALD403 IM, placebo SC, placebo IV

• 100 mg ALD403 SC, placebo IM, placebo IV

• 100 mg ALD403 IV, placebo IM, placebo SC

• 300 mg ALD403 IM, placebo SC, placebo IV

• Placebo IM, placebo SC, placebo IV

Individuals were dosed on Day 1 and at Week 12.

The study evaluated pharmacokinetic and pharmacodynamic endpoints for the administration of ALD403 delivered via each of the three routes of administration.

Key Points

• ALD403 provided a comparable level of suppression of peripheral CGRP biology for a full 3 months when administered via a single intravenous (100 mg), subcutaneous (100 mg) or intramuscular injection (100 mg or 300 mg).
• ALD403 administered via subcutaneous or intramuscular routes of administration had an approximately 80% bioavailability relative to an intravenous infusion.
• Local tolerability via all modes of administration was excellent.
• The safety profile was consistent with earlier ALD403 clinical trials.
• The data support a quarterly dosing strategy as a single injection by all modes of administration.
   

The results of this study provide an important bridge between pharmacodynamic monitoring via peripheral CGRP blockade and migraine prevention: doses (100mg and 300mg) that provided for a full 3 months of migraine prevention in the Phase 2b study of chronic migraine patients also provided 3 months of suppression of peripheral CGRP biology independent of route of administration.

Additional results, including future analysis of additional secondary endpoints, from both of these trials are expected to be presented at upcoming medical meetings and published in peer-reviewed medical journals.

Conference Call and Webcast

Alder will host a conference call at 8:30 a.m. ET today to discuss these clinical trial results. The live call may be accessed by dialing 877-430-4657 for domestic callers or 484-756-4339 for international callers and by providing conference ID number 80096426.

A simultaneous webcast with slides will be broadcast live on the investors section of Alder’s website at www.alderbio.com and will be available for replay following the call for 30 days.

About ALD403

ALD403 is a genetically engineered monoclonal antibody that inhibits calcitonin gene-related peptide, or CGRP, for prevention of migraine. CGRP is a small protein with a well-established role in the initiation, mediation, transmission and heightened sensitivity to pain experienced in migraine. ALD403 was discovered by Alder scientists and has been evaluated in multiple clinical trials evaluating approximately 800 patients. In a proof-of-concept clinical trial evaluating patients with frequent episodic migraine, ALD403 demonstrated significant prevention of migraines, including complete migraine relief (100% suppression of migraine occurrence) in 27% to 41% of patients in any given month. Migraines were completely prevented in 16% of patients for the entire three-month study period. ALD403 also has a favorable emerging safety profile, demonstrating a similar level of safety to placebo, and has been well-tolerated in studies to date. Alder initiated its late-stage clinical trial program in October 2015 with PRevention Of Migraine via Intravenous ALD403 Safety andEfficacy 1 (PROMISE 1), a pivotal clinical trial evaluating patients with frequent episodic migraine. Alder plans to initiate a second pivotal clinical trial, PRevention Of Migraine via Intravenous ALD403Safety and Efficacy 2 (PROMISE 2), in patients with chronic migraine in the second half of 2016. Also in 2016, Alder further plans to enter late-stage clinical development of a self-injected formulation of ALD403 to complement the infusion formulations evaluated in the PROMISE 1 and 2 trials.

About Migraine

Migraine is a common neurological disorder that results in suffering caused by intense sharp or throbbing pain in the head, commonly accompanied by nausea, vomiting and high sensitivity to light and sound.  Over time, patients may be subject to an increasing frequency and severity of migraine attacks, potentially leading to significant disability.

The Migraine Research Foundation estimates that 36 million American adults and children suffer from migraines. According to the American Migraine Foundation, migraine is three times more common in women than men and affects 30% of women over a lifetime. Migraines can severely restrict normal activities and often make holding a job or maintaining a normal lifestyle difficult. The Migraine Research Foundation estimates U.S. employers lose more than $13 billion each year as a result of 113 million lost work days due to migraine.

Currently, preventive medications approved for migraine include beta blockers (such as propranolol), topiramate, sodium valproate and botulinum toxin, or Botox. Medication side-effects, such as cognitive impairment, nausea, fatigue and sleep disturbance, often limit the use of migraine medications, according to the American Migraine Foundation. The U.S. Agency for Healthcare Research and Quality reports that only about 12% of adults with frequent episodic or chronic migraine take preventive medications. Alder believes this creates a significant unmet medical need for new treatments with improved safety and efficacy that can either prevent migraines completely or reduce the frequency to a level where patients can find adequate relief from existing abortive medications.

About Alder BioPharmaceuticals

Alder BioPharmaceuticals, Inc. is a clinical-stage biopharmaceutical company that discovers, develops and seeks to commercialize therapeutic antibodies with the potential to meaningfully transform current treatment paradigms. ALD403, Alder’s lead pivotal-stage product candidate being evaluated for migraine prevention, is a genetically engineered monoclonal antibody that inhibits calcitonin gene-related peptide (CGRP). CGRP is a small protein with a well-established role in the initiation, transmission and heightened sensitivity to migraine pain. Alder’s second program, ALD1613, targets adrenocorticotropic hormone (ACTH) and is intended for the treatment of Congenital Adrenal Hyperplasia or Cushing’s disease. ALD1613 is undergoing Investigational New Drug (IND)-enabling preclinical studies and an IND submission is planned for 2016. Additionally, Alder’s clazakizumab, is designed to block the pro-inflammatory cytokine IL-6 and has completed two successful Phase 2b clinical trials. Alder is seeking strategic opportunities for clazakizumab. For more information, please visit http://www.alderbio.com. 

Forward-Looking Statements

This press release contains forward-looking statements, including, without limitation, statements relating to: the continued development and clinical, therapeutic and commercial potential of ALD403, ALD1613 and clazakizumab; the availability of clinical trial data; future regulatory filings and the anticipated commercialization of ALD403; the initiation of future clinical trials and studies; and the pursuit of strategic alternatives for clazakizumab.  Words such as “support,” “continues,” “potential,” “strategy,” “commitment,” “look forward,” “seeking,” “advancing,” “marketing,” “expected,” “plans,” “initiate,” “further,” “enter,” “believes,” “submit,” “intended,” “designed,” or other similar words or expressions, identify forward-looking statements, but the absence of these words or expressions does not necessarily mean that a statement is not forward-looking.  In addition, any statements that refer to expectations, projections or other characterizations of future events or circumstances are forward-looking statements. The forward-looking statements in this press release are based upon Alder's current plans, assumptions, beliefs, expectations, estimates and projections, and involve substantial risks and uncertainties.  Actual results and the timing of events could differ materially from those anticipated in the forward-looking statements due to these risks and uncertainties as well as other factors, which include, without limitation: risks related to the potential failure of ALD403, ALD1613 and clazakizumab to demonstrate safety and efficacy in clinical testing; the availability of data at the expected times; the clinical, therapeutic and commercial value of ALD403, ALD1613 and clazakizumab; risks and uncertainties related to regulatory review and approval processes and Alder's compliance with applicable legal and regulatory requirements; the uncertain timing and level of expenses associated with the development of ALD403, ALD1613 and clazakizumab; the sufficiency of Alder's capital and other resources; market competition; changes in economic and business conditions; and other factors discussed under the caption "Risk Factors" in Alder’s Annual Report on Form 10-K for the fiscal year ended December 31, 2015, which was filed with the Securities and Exchange Commission (SEC) on February 23, 2016 and is available on the SEC's website at www.sec.gov.  Additional information will also be set forth in Alder’s other reports and filings it makes with the SEC from time to time.  The forward-looking statements made in this press release speak only as of the date of this press release.  Alder expressly disclaims any duty, obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in Alder's expectations with regard thereto or any change in events, conditions or circumstances on which any such statements are based.

Media Contacts:			
David Schull or Lena Evans		
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Investor Relations Contact:
David Walsey
Alder Biopharmaceuticals Inc.
(425) 408-8032
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