Aileron raises $30m to advance second stapled peptide
This article was originally published in Scrip
Aileron Therapeutics will use $30m from a Series E venture funding round to take its second stapled peptide into the clinic after the Cambridge, Massachusetts-based company collected its first set of clinical data from another therapeutic candidate earlier this year.
Aileron has raised almost $100m to date to develop stapled peptides, including $12m in January to fund a Phase I clinical trial for the long-acting growth hormone-releasing factor (GRF) agonist ALRN-5281 (scripintelligence.com, 15 January 2013). The company's second therapeutic candidate ALRN-6924 is designed to reactivate the tumor suppressor protein p53 in solid and liquid tumors by modulating the MDM2 protein, which is activated by other p53-targeting small molecules, and by modulating the harder-to-reach MDMX protein.
Stapled peptides – peptides that are locked into stable, biologically-active shapes so that they can permeate cell membranes – target intracellular protein-protein interactions that can't be modulated with currently available protein therapeutics.
Aileron president and CEO Joseph Yanchik told Scrip that ALRN-6924's ability to modulate both MDM2 and MDMX should give the company's stapled peptide an advantage over drugs investigated by Roche, Merck, Johnson & Johnson, Novartis and other companies that target MDM2 alone. The only approved cancer therapy targeting p53 is Teva Pharmaceutical's Treanda (bendamustine hydrochloride), but Sagient Research's BioMedTracker counts at least 10 other Phase I and II candidates.
Use of proceeds
Most of Aileron's Series E round will fund a Phase I clinical trial for ALRN-6924, which is expected to enter the clinic in mid-2014. The company also will start a Phase Ib trial for ALRN-5281 in the second quarter of next year and it may advance a third compound in late 2015 to treat endocrine and metabolic disorders.
All of Aileron's existing investors backed the company's Series E round, including four corporate venture capital funds. Roche Venture Fund, Novartis Venture Funds, Lilly Ventures and GlaxoSmithKline's SR One invested alongside the private venture capital firms Apple Tree Partners and Excel Venture Management.
"We've had really terrific [investor] interest and participation throughout the life of the company," Mr Yanchik said, noting that Aileron's latest funding round was oversubscribed with investors willing to make cash commitments that exceeded the company's goal.
"Our story has remained compelling for our investors. In this fundraising environment, that's a testament to the value of the platform," Mr Yanchik added.
Life science venture capital investment has been in a herky-jerky pattern in 2013 with first and third quarter totals in the US falling below the same periods in 2012 while second quarter fundraising surged higher on a year-over-year basis (scripintelligence.com, 23 October 2013).
In addition to its venture capital fundraising activities, Aileron continues to speak with potential partners for its stapled peptide platform and individual dug candidates. The company has a partnership worth up to $1.1bn in upfront and milestone fees plus royalties with Roche for development of stapled peptides to treat cancer and inflammation (scripintelligence.com, 21 November 2011).
"We're always having talks with partners and evaluating whether to take things forward with partners or on own," Mr Yanchik said.
Future studies
The Phase Ia study for ALRN-5281 tested single ascending doses in healthy volunteers. There were no serious adverse events, dose-limiting toxicities or drug-related discontinuations. The Phase Ib study will identify potential once-weekly subcutaneous doses for further testing in patients with rare endocrine disorders, including growth hormone deficiency and HIV lipodystrophy.
The Phase I clinical trial for ALRN-6924 will enroll about 100 patients with solid tumors and hematological malignancies. The drug candidate is focused on wild type p53, which is implicated in about 50% of all cancers.
The ALRN-6924 trial will help Aileron identify subpopulations for mid-stage clinical trials and determine whether the drug can overcome toxicity concerns that kept other p53-targeting therapies from moving into Phase II studies, including negative effects on bone marrow.
MDMX modulation appeared to reduce toxicities associated with p53 activation in preclinical studies at the University of California, San Francisco. Aileron's drug candidate will be the first clinical test of the UCSF findings.