When Eliem Therapeutics launched last March, CSO Valérie Morisset said Endpoints News that after being approached to take a leap into biotechnology, she originally intended to “kill her and move on to the next opportunity”. Instead, she joined Seattle biotech in the UK and quickly helped take it public just five months after that sneak exit.
But it looks like Eliem will have to adopt Morisset’s original line of thinking and move on to the next opportunity, as the startup’s lead program failed in a Phase IIa trial in patients with diabetic peripheral neuropathic pain (DPNP). The prodrug, ETX-810, will live in a second indication, with Phase IIa results in lumbosacral, or sciatica, radicular pain slated for the third trimester.
This is just part of the one-two punch leaked Monday morning, sending Eliem’s stock $ELYM down 52% before the opening bell.
The second obstacle to Eliem’s rapid rise: the company is delaying the enrollment of another drug, ETX-155, in phase IIa trials in various indications of depression due to pharmacokinetic data from a trial phase Ib in patients with photosensitive epilepsy.
“The failure of the ETX-810 DPN trial is disappointing, and for ELYM stocks, it removes one of the key potential upside drivers. However, we still believe there is hope for the ELYM’s ongoing ETX-810 LSR/sciatica trial – to read in 2H22 – as sciatica is the only indication where there is the strongest clinical precedent for PEA,” Stifel analysts wrote in a note.
Eliem CEO and Chairman Bob Azelby in a press release called the results “unambiguous”, noting that there is no development path for ETX-810 in DPNP. The active is a prodrug of the bioactive lipid palmitoylethanolamide, or PEA.
“Given previous positive clinical data for the mechanism of action of ETX-810 in multiple neuropathic pain populations, it is unfortunate that we were unable to confirm a benefit in the DPNP patients studied in this trial. We believe that all aspects of this trial were well executed, with appropriate patient selection, well-balanced study arms, and a placebo effect consistent with expectations,” said Azelby.
The flop of DPNP was the result of the prodrug’s inability to separate statistically significantly from placebo on the primary endpoint, which was a change from baseline at week 4 in weekly mean daily pain, as assessed by a rating scale. So Eliem’s hopes are now pinned on the sciatica trial.
“We note that while we believe there was reasonable evidence in the PEA literature supporting efficacy in both indications, there is more direct evidence for efficacy in LSRP. Additionally, it should be noted that Eliem saw a clean overall security profile for [‘810] during the DPNP study, in line with expectations,” the Stifel analysts wrote.
The second half of the double-whammy news fall is that Eliem’s ETX-155 appeared to have “lower than expected drug exposure,” in a Phase Ib study in patients with photosensitive epilepsy, Morisset said in the press release. The discovery led the company to delay enrollment in its Phase IIa studies of the drug in major depressive disorder and perimenopausal depression. So far, three patients have been evaluated in the phase Ib study, showing that drug levels were “significantly lower than expected” following the pharmacokinetic profile seen in two phase I trials.
“[T]The other disappointment, considerably more surprising this morning, is the confounding of data from ELYM’s ph1b photosensitive epilepsy study for ETX-155. We had considered this trial as medium level catalyst (i.e. likely to be positive, but more gradual), but ELYM is delaying further studies (MDD/PMD) for ‘155 as they observed exposures drugs weaker than expected. While we await more information, this situation is difficult to verify,” Stifel analysts wrote in their note.
Eliem is investigating the “potential root causes for the observed difference in exposure compared to previous studies, including assessing any differences between the batches of drug products used in this study and those in previous Phase 1 trials,” said biotech.
Biotech reiterated that it is “well capitalized to fund the business through multiple additional catalysts.” Eliem “does not anticipate any layoffs at this time,” a company spokesperson told Endpoints in an email, noting that the biotech has about 30 full-time employees.