There is considerable room for innovation in neuropsychiatric drug development and Palomar Labs, a venture studio, is hoping to capitalize on that by building companies around drug candidates with prior human validation. As Shlomi Raz, a managing partner at Palomar Labs, explained it, the company’s “mission is to find promising drug candidates with some history of human use” that specifically target “conditions associated with late life.” The goal is to take candidates, which already have some documented evidence of safety and efficacy, through the clinic and through to proof-of-concept.
And now the venture studio, which was formerly called Negev Labs, has made its first move towards those goals by spinning out its first portfolio company, Ariadne Bio, with a lead program already in hand. Raz steps into the role of CEO for the company and Daniel Jeffries, PhD, a partner at Palomar Labs, will take on the role of chief development officer for the company. Ariadne Bio will focus on developing AB-300, a clinical-stage molecule that functions as a non-hallucinogenic serotonin 2A receptor agonist. The company is developing the molecule to treat apathy in people with Parkinson’s disease.
“A significant portion of people with Parkinson’s will lose the drive to do the things that make life worth living, and not a single approved medicine is designed to bring it back,” Raz said. “We built Ariadne Bio around a single question: whether motivation can be restored pharmacologically. AB-300 is how we intend to answer it.”
Ariadne Bio makes a compelling case for targeting apathy. As Jeffries notes, “apathy is among the most disabling non-motor features of Parkinson’s disease.” The condition is defined clinically as a persistent reduction in goal-directed behavior. It is estimated to affect approximately 40% of people with Parkinson’s disease over the course of the illness.
Higher rates of the condition are reported in people in the mid to late stages of the disease. In fact, studies of caregiver burden in Parkinson’s rank neuropsychiatric symptoms like apathy ahead of motor symptoms as drivers of distress. It is important to note here that while apathy and depression have some overlapping features, they are distinct conditions. Selective serotonin reuptake inhibitors (SSRIs) remain the appropriate treatment for Parkinson’s associated depression, but some evidence links their use to emotional blunting and worsening apathy.
In contrast, there are currently no approved therapies for apathy in any indication. If AB-300 successfully makes its way through clinical trials and clears regulatory approval, it could be one of the first. And Raz and his team are driven to accomplish that goal. In fact, this is the second neuropsychiatry-focused company that Raz is launching. Previously, he founded Eleusis, which claims to be the first company that was dedicated to developing medicines derived from psychedelic compounds. Eleusis was acquired by Beckley Psytech in 2022. That company combined Atai Life Sciences to form AtaiBeckley in 2025. As of July, 2026, Eli Lilly entered into a definitive agreement to acquire AtaiBeckley.
A non-hallucinogenic history
Raz moved to Palomar Labs after a stint at Beckley Psytech because of what he saw as a “significant opportunity” with similar themes to psychedelics—drugs with demonstrated therapeutic potential that never translated into U.S. Food and Drug Administration-approved therapies. There are several drugs that could fall into this category but Raz admits he is a bit biased towards serotonin therapies because of his background in psychedelics. “Coming out of the psychedelic space, the way I view it is that the first generation of that drug class were these very potent classical psychedelics like psilocybin and LSD,” he said during the conversation. The second generation featured drugs with formulation changes that altered their pharmacodynamics in different ways.
Raz and his team are most interested in what he categorized as the third-generation. These are potential therapies that activate the same receptors as psychedelic drugs without the corresponding hallucinogenic effects, making them ideal for use in older adults. AB-300 is one such compound. For some of its back story, the compound is based on one that was previously tested in the 1970s and documented to lack hallucinogenic effects, Jefferies told GEN. Since then, several groups have dug into why this particular molecule does not cause hallucinations like other serotonin agonists.
Earlier this year, scientists published a paper in January in Nature that pointed to signaling bias as the likely reason. “When you activate serotonin 2A, there’s multiple intracellular pathways that can be engaged,” Jeffries said. According to the paper’s findings in a preclinical model, the parent compound that AB-300 is based on “preferentially activated the non-hallucinogenic pathway” without removing any therapeutic benefit.
The fact that this compound does not act on dopamine receptors is crucial. “Classically, mental stimulation comes through a variety of drugs that either block the re-uptake of dopamine or activate dopamine receptors directly,” Raz notes. “The problem of course is that they aren’t necessarily well tolerated by older adults. And so we saw the promise of developing a therapy that indirectly modulates motivation through serotonin receptor activation” without the hallucinogenic effects. Apathy in Parkinson’s disease cases is the immediate target but Raz acknowledged that there are other diseases of aging that involve unaddressed apathy. And Ariadne Bio is actively exploring ways to address those conditions in future. “The more research we did, the more we realized how profound the unmet need there was.”
Building up to Phase Ib
In May 2026, at the American Society of Clinical Psychopharmacology, (ASCP) Ariadne Bio presented results from tests of its lead candidate in a preclinical model of tetrabenazine (TBZ)-induced motivational deficit, assessed by progressive-ratio lever pressing. In this model of effort-based motivated behavior, AB-300 plus TBZ increased motivational behavior by 89% relative to the TBZ only group, which is a statistically significant improvement.
The company claims that AB-300 is the first serotonin 2A receptor agonist drug candidate shown to restore motivated behavior in a dopamine-depleted model. They also claim that in off-target screening, AB-300 shows no measurable activity at dopamine receptors or the dopamine transporter, which indicates that it engages motivational circuitry through a mechanism independent of dopaminergic signaling.
Raz and Jeffries dug into the details of the study using the tetrabenazine-induced model in more detail during their conversation with GEN. “One of the interesting things about developing apathy, is that this indication has an in vivo model that’s arguably more translatable than some of the other more mainstream neuropsychiatric indications,” Jeffries explained. Tetrabenazine is an FDA-approved drug used in Huntington’s disease with detailed data on its ability to induce a low motivational apathetic phenotype in clinical and preclinical models. Part of what makes the drug so interesting is that it depletes the levels of circulating dopamine in the brain, similar to what is seen in Parkinson’s cases.
That is an important point, Jefferies emphasized. Because “essentially what that allows developers to do is to test their investigative agent in a motivational model with the background of dopamine depletion,” he said. In terms of the results, the team saw positive effects at doses that are predicted to be within a therapeutic range in the clinic. Furthermore, the team also observed some of the negative effects of using SSRIs to treat apathy in their model. These results mirrored clinical observations of patients, whose apathy was treated with SSRIs and saw their symptoms worsen. These results show the efficacy of AB-300 and “it’s giving us a lot of motivation … to move forward,” he added.
That next step is a Phase Ib clinical trial that will test AB-300 in healthy volunteers and Parkinson’s patients, most of whom will be receiving the current standard of care treatments and potentially on antidepressants for their apathy. In addition to assessing safety and efficacy of the treatment, Ariadne’s team and their partners will also assess potential interactions between their compound and those other drugs.
The trial will begin likely at the end of Q3 or the beginning of Q4 at centers in Austria and Israel. Ariadne Bio has already had a Type B pre-IND meeting with the FDA regarding the development of AB-300 for Parkinson’s disease-associated apathy.
The planned trial will be a three-part study, Jeffries told GEN. The first part will be a single ascending dose in healthy patients followed by a single ascending dose in Parkinson’s disease patients. In both parts, the scientist will explore “a variety of biomarkers [and a] range of doses” to identify the maximally efficacious dose. “We have the preclinical data [that] tells us generally where we should be looking, but we need to really see that in patients who are on Parkinson’s disease medications to confirm that in fact that is the right range for what we anticipate to be a clinically effective dose or at least to evaluate that potential,” Raz added. The third part of the trial will be a 28-day placebo-controlled double-blind of AB-300 against placebo in patients with clinically relevant apathy.
Ariadne Bio’s launch is backed by funding from Palomar Labs as well as from The Michael J. Fox Foundation through its Parkinson’s disease therapeutics pipeline program. That program supports preclinical and translation research aimed at evaluating promising therapeutic approaches and helping to support their clinical development. While Ariadne officials declined to disclose exactly how much it has received in funding, Raz told GEN that the company has enough in house to complete the proposed clinical trial at this time.
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