Staff Writer

Biotech start-up Arteaus Therapeutics LLC raised $18 million in a Series A financing from Atlas Venture, of Cambridge, Mass., and OrbiMed Advisors, of New York, to advance a migraine headache antibody technology licensed from Eli Lilly and Co.

The calcitonin gene-related peptide (CGRP) antibody could become the first antibody therapy to prevent migraine headaches. Cambridge, Mass.-based Arteaus licensed global rights to develop the technology from Lilly, of Indianapolis, in a collaboration that leverages the pharma company's development experience with the biotech's capital-efficient business model to pursue clinical proof of concept.

Positive data from a Phase I single-ascending dose study supported the decision to move forward with the antibody's development and met the criteria to proceed with a multidose cohort expansion to determine safety, pharmacokinetics and pharmacodynamics, according to David Grayzel, CEO of Arteaus and managing director of Atlas Venture Development Corp. (AVDC).

Arteaus – whose name harkens to 2nd Century Greek physician Aretaeus, who first described the hallmark symptoms of migraine – plans to begin the multidose portion of the study at the end of this year and is on track to begin a Phase II proof-of-concept study in mid-2012, Grayzel said. He estimated that study will take 12 months to 15 months to complete.

"At that point, we'll have a very good handle on whether or not the drug is active, and we're hoping to see a robust proof-of-concept signal," Grayzel told BioWorld Today.

The collaboration between Arteaus and Lilly is the first in the AVDC portfolio, created to "increase the velocity of capital" and "make more discreet asset-centric shots on goal," explained Grayzel, who joined AVDC when it was launched by Atlas 18 months ago. AVDC's goal is to partner with pharmaceutical and biotech companies to develop entities that can take late preclinical and clinical-stage programs to key "value inflection points," enabling larger players to expand their development pipelines without building programs internally.

AVDC examined nearly 200 therapeutic programs that met its criteria – high-value assets that could achieve proof of concept on $12 million to $18 million – when it settled on the CGRP antibody as its first licensing deal and launched Arteaus in June.

Twenty years of clinical evidence suggests that CGRP plays an important role in the pathophysiology of migraine, Grayzel explained, noting that several small-molecule receptor antagonists have shown efficacy in small Phase II studies even though none has succeeded to approval.

The antibody under development by Arteaus seeks to block CGRP from binding to its ligand, preventing the vasodilation and pain transmission in the brain that characterize migraine and, thus, preventing the debilitating headaches themselves.

"We're excited to test that hypothesis in a Phase II trial looking at patients who are frequent migraineurs – who have more than four and sometimes up to 10 migraine headaches per month – to see whether we can make a significant reduction in the frequency of migraines and the number of headache days they experience per month," Grayzel said.

The antibody approach also may allow the development of a monthly subcutaneous injection, comparable to other antibody formulations. Although designed as a prophylactic, an injectable could have some advantages for migraine patients, since the nausea and vomiting that often accompany migraine episodes tend to limit the effectiveness of oral therapies.

With an investigational new drug application filed, Arteaus is relying principally on its virtual team of researchers and consultants to manage the program through Phase II. However, the company has the option to collaborate with Lilly's Chorus – an autonomous unit that focuses on early drug development through proof of concept – to maintain continuity and leverage the team's knowledge of the antibody and the migraine market, Grayzel said.

The Series A round will provide sufficient capital to move the compound through Phase II, he added.

At that point, Lilly will have the option to take back responsibility to develop the CGRP antibody through late-stage clinical trials at prenegotiated milestones and royalties, which Grayzel declined to specify. Both partners view that outcome as optimal, he said, with a successful Phase II likely serving as the exit for Arteaus.

"The goal here is to create an entity that is able to very quickly move this asset from its IND filing to its POC," Grayzel said.

If Lilly declines to reclaim the migraine compound, Arteaus has the option to pursue another buyer or fund the company for additional clinical trials.

The market opportunity is significant, with more than one in 10 Americans suffering from migraines and nearly one-third of migraineurs reporting three or more attacks per month, according to a study sponsored by the National Headache Foundation. Although some progress has been made in treating migraines with triptans and other acute migraine medications, "there hasn't been nearly as much success in trying to find ways to prevent migraines," Grayzel said.

In fact, the triptan market is increasingly crowded, with more than half a dozen branded products sold in the U.S. for the treatment of acute migraine, led by GlaxoSmithKline plc's Imitrex, which in 2007 had sales of about $1.2 billion in the U.S. and $1.6 billion worldwide, according to data published by IMS Health. (See BioWorld Today, Aug. 7, 2009.)

Some biotechs are seeking to enter the acute migraine market using other approaches. For example, MAP Pharmaceuticals Inc., of Mountain View, Calif., is developing Levadex, a self-administered, orally inhaled therapy for acute migraine in adults. MAP is in a marketing deal for Levadex with Allergan Inc., of Irvine, Calif., which markets Botox to headache specialists for the treatment of chronic migraine. (See BioWorld Today, Feb. 1, 2011.)

Nevertheless, Arteaus has few competitors in the prophylactic migraine space – particularly following the Phase IIb failure of gabapentin enacarbil (XenoPort Inc., GlaxoSmithKline) for migraine prevention. (See BioWorld Today, July 8, 2010.)

AVDC hopes to lead that class while forging a new business paradigm to develop promising therapeutic candidates.

"This is a very interesting model for us, and we'll be actively pursuing other collaborations and looking for other assets to place into similar structures," Grayzel said. "The key is that the actual structure is flexible and can meet the needs of the pharma/biotech partners as well as the venture capital syndicate."