Alto Neuroscience adds third Phase 3 trial for ALTO-207, cites Nature Medicine data

Alto Neuroscience said in its second-quarter 2026 results that in July 2026 it disclosed plans to speed up and broaden clinical development of ALTO-207, adding a new Phase 3 trial to test the drug as monotherapy in treatment-resistant depression (TRD)¹. The company said a monotherapy dataset, combined with the planned adjunctive Phase 3 trial, could support a wider label and larger addressable population for ALTO-207 if approved¹. Alto expects to start this trial, called PACE-3, in the second half of 2027, pending FDA alignment¹.

The two other studies in the program remain on track. The Phase 2b adjunctive TRD trial, PACE-1, is enrolling roughly 178 adults and uses MADRS as its primary endpoint, aligned with FDA standards, with topline data expected in the second half of 2027¹. The Phase 3 adjunctive trial, PACE-2, is set to begin by early 2027 following FDA alignment on design, and will run in parallel with the Phase 2b trial rather than wait for its results¹.

Supporting the mechanism, Alto pointed to an independent Lund University trial called PRIME-PRAXOL, published in Nature Medicine in June 2026, in which pramipexole added to treatment reduced anhedonia significantly more than placebo on the SHAPS scale (mean difference −4.04; p=0.006; Hedges' g=0.62) in patients with depression and anhedonia¹. Nausea occurred in about 60% of the pramipexole arm despite slow titration, the tolerability issue ALTO-207's fixed-dose design is meant to address¹.

On financing, Alto completed a registered direct stock offering in July 2026, selling 3,776,436 shares at $26.48 each for about $100.0 million gross and $94.6 million net¹. Including those proceeds, pro forma cash stood at approximately $338 million¹, which the company said positions it to pursue ALTO-207 in both adjunctive and monotherapy settings, with runway expected through 2030¹.