Neumora readies three PhIII trials for depression drug under new CEO

The wheels are rolling fast at Neumora as the “Really Big Neuroscience Company” nears three Phase III trials for its investigational depression drug, readies a slate of other clinical studies and woos a new CEO from Big Pharma.

Neumora said Tuesday morning it hired Henry Gosebruch as president and CEO. Gosebruch, AbbVie’s former chief strategy officer, joined July 3 and takes the place of Paul Berns, who transitioned to executive chair.

It also unveiled plans for three late-stage studies for its major depressive disorder candidate navacaprant, beginning with a US trial this quarter and a pair of global studies set to start by year’s end and in the first quarter of 2024.

With about $400 million on the balance sheet at the end of 2022, finance chief Joshua Pinto told Endpoints News that Neumora has plenty of cash to take it into 2025, the year it anticipates requesting navacaprant’s approval as a monotherapy.

Paul Berns

By that point, Neumora expects to be well along with multiple drug programs. Berns said in an interview that the company plans to move a V1aR antagonist for anxiety disorders into mid-stage testing next year; investigate a CK1δ asset in an early-stage trial for amyotrophic lateral sclerosis and then likely certain Alzheimer’s patients; and enter a muscarinic receptor 4 molecule into a Phase I for schizophrenia. (Karuna and Cerevel are developing similar treatments for schizophrenia.)

The 125-employee startup is expecting to hire a chief commercial officer, Berns said. Neumora can run all its programs in-house, but biopharmas have expressed interest in its pipeline, which Berns doesn’t see letting up as he hands the keys to Gosebruch.

The new CEO brings experience in MDD drug approvals. He departed AbbVie in February after seeing the Chicago-area drugmaker nab FDA approval for Vraylar as an adjunctive to antidepressants in adults with MDD last December.

In a prepared statement, Gosebruch said Neumora is “at the forefront of a new era in neuroscience” and is poised to take on the “global brain disease crisis” with new approaches.

A Phase III push into depression

In MDD, Neumora has an oral kappa-opioid receptor antagonist. While Johnson & Johnson’s Janssen is already investigating such a drug in Phase III, Neumora is eyeing a monotherapy label as compared to the Big Pharma’s adjunctive approach.

The kappa-opioid receptor is involved in a system that impacts stress.

“The idea of selective targeting of that system [is it] can improve function in stress-related circuits that are important in motivation and reward,” Sanjay Mathew, a Neumora consultant and psychiatry and behavioral sciences professor at Baylor College of Medicine, said in an interview.

Neumora’s expansive Phase III studies, dubbed KOASTAL-1, -2 and -3, will test 80 mg of the once-daily oral drug in adults with moderate-to-severe MDD. At week six, researchers will assess change from baseline on a measure known as the Montgomery-Asberg Depression Rating Scale (MADRS). Janssen is employing the same primary endpoint scale in its Phase III studies, which are slated for completion in 2024.

Sanjay Mathew

Patients’ MADRS total score must be at least 25 at baseline to gain entry into Neumora’s trials. About 350 patients will be enrolled in each of the trials, chief development officer Bill Aurora said in an interview.

In Phase II, investigators tested for shifts in depression on a different scale, known as the 17-item Hamilton Rating Scale for Depression. Neumora’s navacaprant reported drops of 3.0 at week four and 2.8 at week eight, coming in at p-values of 0.015 and 0.037, respectively, for moderate-to-severe patients.

But when looking at the entire study population, which included mildly depressed people, the study did not achieve statistical significance compared to placebo on the primary endpoint at week eight, coming in at a p-value of 0.121. The Phase III trials will not include mildly depressed patients.

The drug comes from BlackThorn Therapeutics, which designed the mid-stage study. ARCH founded both companies, with the South San Francisco-based BlackThorn reeling in $54 million in Series A funds from the VC firm, GV and others.

Neumora completed a successful end-of-Phase II meeting with the FDA last month, Aurora said, emphasizing the company hopes to replicate mid-stage results showing patients had no weight gain or sexual dysfunction, which are common concerns for other depression drugs.

Bill Aurora

Changes in anhedonia, when a person experiences a major lull in pleasure, will be a key secondary measure in the sweeping Phase III program. About 70% of people with MDD report anhedonia, Aurora said.

What’s next for navacaprant — and MDD

Patients in the studies can move into an open-label extension so Neumora can provide regulators with long-term safety data. Eventually, Neumora or investigator-initiated studies could explore navacaprant’s potential in people with substance use disorder, bipolar depression, PTSD and other indications, Aurora said.

By the time Neumora’s KOASTAL program sets sail, Sage Therapeutics and partner Biogen may know whether the FDA has approved their MDD and postpartum depression drug zuranolone. The oral, rapid-acting drug has a PDUFA date of Aug. 5. Meanwhile, Axsome Therapeutics secured an FDA green light last August for Auvelity.

“The field has been plagued by a lot of high placebo responses and negative studies, or inconclusive studies,” said Mathew, the Baylor professor who has helped design Neumora’s studies.

For the new trials, “first and foremost, you want successful replication of a reasonably large effect size with the primary endpoint,” he said. “The safety data from Phase II was quite reassuring.”

If the trials pan out, it will be really big, just as ARCH managing director Bob Nelsen and Neumora’s founders intended.

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