Applying “de-risked” compounds as potential medicines for rare diseases in brain development
AMO Pharma is a private company developing compounds it has found and identified as candidates to treat rare childhood diseases in brain growth and function. The company selects pipeline drugs with sufficient prior research data to indicate their readiness for human clinical trials rather than for a particular drug mechanism or therapeutic platform. Its three lead drugs are now at the clinical stage: the furthest along is AMO-02 (tideglusib), now in Phase 3 for congenital myotonic dystrophy; next is AMO-01 (diazepinomicin), in Phase 2 for Phelan-McDermid syndrome; and AMO-04 (tianeptine), in Phase 2 for Rett syndrome.
WHAT’S AT STAKE
The measure of what a company has at stake is proportional to the newness of its core concept. But the most-often seen novelties in the biopharma industry — innovative mechanisms, compositions of matter, formulations, or technology platforms — may no longer be so novel. Instead, they may have become something we expect, along with their high risk of investment. Perhaps another productive but more risk-free path is possible. AMO Pharma believes it has embarked on one.
When CEO Ibraheem Mahmood and CSO Dr. Michael Snape cofounded the company in 2015 after decades in the clinical trials business, they deliberately aimed to depart from the prevailing model for bio startups. “We were not interested in finding some interesting science, moving it into a later stage, and then selling it to a major pharmaceutical company that might do something with it,” says Mahmood. “We want to actually bring drugs all the way to market, and that’s hard to do, and it’s really risky. The whole philosophy of the company is to bring life-changing medicines to the world and manage the risk at the same time.”
He says the company manages risk in three ways: “First, we don’t believe in developing medicines that haven’t already been in humans to some extent. The No. 1 reason drugs fail is side effects. Second, we only go after rare diseases, which are less risky because the regulator environment is more supportive and most rare diseases worth going after are severe, so it’s easier to have a therapeutic effect. Third, we are entirely focused on diseases impacting the CNS. Historically, people have said CNS has a very high drop-out rate in clinical trials, making it high risk. But our view is that clinical success in CNS diseases is all about getting the clinical trial design right. You can design a trial that can pick up the most meaningful signal in your drug.” (See “AMO Pharma Works With FDA To Advance CNS Trials,” Clinical Leader, November 2020.)
AMO’s central focus now is the development of the brain in children, something that determines movement, behavior, and cognition. Rather than selecting therapeutic compounds through its own invention, however, the company searches out existing drugs with good safety records and therapeutic potential for the rare diseases within its narrowly defined target area. The entire process includes the most advanced tools available, from rational drug design to more detailed mechanistic inquiries, all to understand the full potential of a given drug and its related compounds. Otherwise, the company is agnostic about preferred approaches and pragmatic in its choice of development candidates. Lead drug AMO-02 is based on a former cancer-drug candidate with potential to shift synapse creation to neuron production; it crosses the blood-brain barrier but accumulates where it was ineffective in treating cancer, yet had “stunning” results in patients with congenital myotonic dystrophy.
Some of the mechanisms AMO’s drugs employ have obvious potential for treatment of nonrare diseases, such as autism. For now, though, the company is sticking with orphan indications and letting other possibilities play out over time — another good strategy for limiting development risk by this company to watch.
Employees: 10 Headquarters: London
$60 million private equity
Latest Updates May 2021: Additional Clinical Trial Sites Activated for Pivotal REACH-CDM Study in Congenital Myotonic Dystrophy (CDM1) evaluating efficacy/safety of AMO-02.