Novartis Joins Ensemble To Develop An Oral IL-17 Blocker
This article was originally published in The Pink Sheet Daily
Executive Summary
Novartis is the latest big pharma to partner with Ensemble to develop oral small molecules against traditional biologic targets. Novartis will develop Ensemble’s synthetic macrocycle drug targeting IL-17, a pathway the big pharma knows well.
Ensemble Therapeutics Corp. has partnered its most advanced internal program, a novel oral small molecule targeting the inflammatory cytokine interleukin-17, with Novartis AG. The discovery-stage deal is early compared to a partnership for a clinical asset, but for Ensemble it reflects a valuable partnership at an important inflection point for the technology.
The deal, announced Aug. 5, is different from the many other pharma partners Ensemble has signed in that it is the first time the biotech has partnered its own internally-developed candidate. The company has signed several earlier-stage deals in which a pharma partner has come to Ensemble with a target of interest and the company has used its macrocyle discovery platform to identify leads.
The upfront value of the deal with Novartis, while undisclosed, is the most significant upfront cash the company has brought in through deal-making, CEO Michael Taylor said.
“With the kind of programs and targets we are involved in, these protein-protein interactions tend to be undruggable to small molecules with other platforms, so we build a lot of value into these programs very early in the discovery/development timeline,” he said. “As we look at the deal with Novartis around IL-17, it’s a program that demonstrated a unique orally active small molecule approach to what is otherwise a clinically validated and very valuable target. It allows us to get a deal that is more valuable to us.”
Drugs blocking IL-17, for example, have already demonstrated proof-of-concept in the treatment of autoimmune disease. But those products are biologics that are administered by injection. The value of Ensemble’s discovery platform then is in the creation of an oral molecule that targets that pathway.
Ensemble will receive an undisclosed upfront payment from Novartis and is eligible to receive potential development and sales milestones, as well as tiered royalties on sales of any products that arise from the collaboration. Novartis will also provide research funding under the terms of the collaboration.
The structure is similar to the other partnerships the privately-held company has signed. Those too have included an upfront payment, milestones and R&D funding. The company’s other partners are Pfizer Inc., Bristol-Myers Squibb Co., Genentech Inc., Boehringer Ingelheim GMBH and, most recently, Alexion Pharmaceuticals Inc.[See Deal]. Ensemble has disclosed financial terms for only one deal, signed in 2009 with Bristol, which paid $5 million upfront and $7.5 million in research funding plus milestones in a deal covering up to eight targets [See Deal].
Ensemble’s discovery platform has resulted in a library of more than five million synthetic macrocycle compounds, which it calls Ensemblins. Those compounds are orally available and can permeate cells like small molecules do, and, like biologics, also bind to protein targets. The drugs are designed to reach targets, like protein-protein interactions, that are difficult to drug using traditional methods (Also see "Ensemble Therapeutics Corp." - Scrip, 1 Mar, 2011.).
An Oral In A Crowded Field Of Biologics
Novartis’ interest in an oral IL-17 blocker is straightforward. The company is one of the leaders in the area of research and has a biologic drug that blocks IL-17, secukinumab, poised for a near-term regulatory filing. In July, Novartis reported that secukinumab demonstrated superior efficacy to Amgen Inc.’s Enbrel (etanercept) in treating psoriasis in a Phase III clinical trial. But the field is stacking up to be fiercely competitive with two other IL-17 blockers in Phase III development for psoriasis, Amgen/ AstraZeneca PL’s brodalumab and Eli Lilly & Co.’s ixekizumab (Also see "Psoriasis Market Snapshot: An Area Drug Makers Are Itching To Get Into" - Pink Sheet, 23 Jul, 2012.). An oral drug with a similar safety and efficacy profile to the injectable biologics would stand out from the pack.
“We expect the molecules to perform from a biochemical and clinical perspective very similar to the biologics because they have exactly the same mechanism,” Taylor said.
Il-17 blockers are also being studied to treat other immune-mediated diseases including arthritis and multiple sclerosis. Novartis has the option to study the drug across multiple autoimmune indications, Taylor said.
A molecule could be ready to enter the clinic soon. “When we were working on this independently, we were targeting a development candidate by the end of this year,” he said, though now Novartis will control the timing and will probably need additional time to absorb the program.
Ensemble will work collaboratively with Novartis but will transition the bulk of the research work to the big pharma. Ensemble plans to focus on its three active discovery collaborations and will redeploy resources to discovering another internal candidate that it will eventually partner at around the same phase of development as the IL-17 blocker.