Alto Neuroscience : Corporate Presentation

Published: 2026-05-13 09:04:11 ET ANRO

Published on 05/13/2026 at 09:04 am EDT

NYSE: ANRO

for the Brain is Here.

Precision Medicine

OUR MISSION

Redefining psychiatry by leveraging individuals' neurobiology to develop personalized and highly effective medicines, helping patients get better faster.

Alto by the numbers

Advancing

a leading, clinical-stage precision medicine portfolio for the brain

Patients Dosed

Across studies with Alto's novel product candidates and precision approach

MILLION

Patient Impact

Opportunity across the portfolio

Late-Stage Data Readouts

In next ~3 years

Through

Expected Cash

Runway

Unmet needs pervade mental health disorders

Depression and schizophrenia are leading causes of disability worldwide

Lancet, 2017

13% of U.S.

adults take antidepressants

Brody, 2020

$280bn spent on mental health services in 2020

SAMHSA

Alto's strategy addresses a core problem in psychiatry

Characterizing drug activity and identifying responsive patient populations before advancing

Current approach

Unguided trial-and-error treatments in heterogeneous populations work poorly

Alto precision approach

Differentiated drug profile in stratified patient populations

No human target engagement

Uncontrolled and unmeasured patient heterogeneity

Broad utilization of pharmacodynamic biomarkers

Discover and prospectively replicate objective biomarkers for patient selection

First biomarker-driven pipeline for mental health conditions

Multiple independent programs leveraging our biomarker strategy to systematically reduce development risk; all programs remain on track to achieve upcoming milestones

Product Candidate (MOA/Target)

Phase 1

Effects

Lead Indication Safety s Brain

Phase 2

Clinical Effect in Biomarker Positive

Phase 3

Registration Trial(s)

Next Anticipated Milestone

ALTO-207

(D3/D2 C 5-HT3)

TRD Potentially Pivotal Study*/Phase 2b ongoing & Ph. 3 Planned

Ph. 2b Topline data 2H 2027

Ph. 3 Initiation planned by early '27

ALTO-300

(MT1/2 C 5HT2C)

MDD

Phase 2b Ongoing

Topline Data 1H 2027

ALTO-100

(BDNF)

ALTO-101

(PDE4)

ALTO-203

(H3)

ALTO-202

(NMDA NR2B)

ALTO-208

(D3/D2 C NK-1)

Bipolar Depression Phase 2b Ongoing

Cognitive Disorders^

MDD

Parkinson's Disease

Topline Data Mid 2027

^Fast Track Designation in CIAS 77

*Study qualifying as pivotal is subject to FDA feedback and review of data

A potential best-in-disease treatment for TRD

ALTO-207: combining a dopamine D3-preferring D3/D2 agonist with demonstrated antidepressant effects and 5-HT3 antagonist designed to reduce dose-limiting AEs

ALTO-207

(D3/D2 agonist C 5HT3 antagonist)

pramipexole ondansetron

Dopamine

Neuron

D2 receptor (similar effects in prefrontal and limbic areas)

Novel antagonistic combination:

D2/D3

Gut input

5-HT3 receptor

Nucleus accumbens

Striatal Neuron

D3 receptor

Akt MAPK

Transcription (CREB)

Plasticity Reward

↑ D3/D2 agonism for

antidepressant effects

↓ 5-HT3 activity to reduce dose-limiting AEs

CTZ

Vomiting center

Nausea/Vomiting

CTZ: chemoreceptor trigger zone

Midbrain

ALTO-207 is a novel, clinically validated, and differentiated product candidate for a high-need patient population

Pramipexole has shown robust antidepressant effects across numerous clinical

studies; but is limited by significant tolerability issues

ALTO-207 improved the tolerability of pramipexole, thus achieving higher doses

with 5x faster titration, resulting in large antidepressant effects

A potentially pivotal Phase 2b* is ongoing with topline results expected in 2H 2027. Phase 3 launch is planned for early 2027

Combination products in psychiatry have been validated commercially, and

ALTO-207 has strong patent protection

*Study qualifying as pivotal is subject to FDA feedback and review of data 10

Pramipexole shows one of the largest antidepressant effect sizes reported in TRD (d=0.87) in the peer-reviewed PAX-D publication

Alto meta-analysis, including nearly 500 patients, demonstrates robust antidepressant effect and significant dose-response of pramipexole across clinical trials in mood disorders

Meta-analytic results support pramipexole having the largest antidepressant response

ALTO-207 Phase 2a (4.1mg)

Cohen's d effect size (drug - placebo)

1.1

0.9

Consistent clinical efficacy

PAX-D TRD study (n=150): striking and sustained efficacy

ǪIDS-SR1Cchange converts to a

MADRS Δ of 7. 4 points

0.8

0.7

0.6

0.5

0.4

Pramipexole

(2.08mg avg)

Current SOC

psychedelic

Clear dose-response for pramipexole (p=0.027)

d=0.87

0.3

0.2

0.1

clinical significance (d=0.25-0.3)

Browning et al., Lancet Psychiatry, 2025

Interactive meta-analysis of pramipexole in depression results available here

Note: Effect sizes esketamine and aripiprazole from Wang et al., Medicine, 2023; Jawad et al., Exp Op Drug Saf, 2022; efficacy of other adjunctive antipsychotics is similar to

aripiprazole (Wang et al). Effect size from the two COMP3c0 Phase 3 studies estimated from available information. The results above are not based on head-to-head trials 11

between the products or product candidates. Study designs and protocols differed, and results may not be comparable.

Pramipexole has exhibited field-leading effects on anhedonia, demonstrating potential to address a critical unmet need in depression

0.7

0.6

0.62 0.63

Comparative Effect Sizes on Anhedonia

Cohen's D on Anhedonia (SHAPS unless noted)

0.5

0.4

0.42

0.44

0.31

0.3

0.2

0.1

0.07 0.05 0.05

PAX-D PRIME-PRAXOL

Pramipexole

X-NOVA (Ph. 2) Murrough IIT

XEN1101

Phase 2 PoC

(Nat. Medicine)

Phase 2

(NPP)

Ventura 1 (Ph. 3) -

DARS (no SHAPS)

Aticaprant

Ventura 2 (Ph. 3) -

DARS (no SHAPS)

KOASTAL (Ph. 3)

Navacaprant

Note: The results shown above are not based on head-to-head trials between the products or product candidates. Study designs and protocols differed, and results may not be comparable.

Clear C consistent effects on anhedonia provide strong differentiation and support for ALTO-207

Sources: Browning M. et al., Lancet Psychiatry (2025); Lindqvist D. et al., PRIME-PRAXOL Preprint (2025); Butterfield N. N. et al., JAMA Netw Open (2025) - azetukalner, K7 opener

in MDD.; Fremont et al. ASCP poster 2025; Krystal A. D. et al., Nat Med (2020), Schmidt M E et al., Neuropsychopharmacology ( 2024); Popova et al. 2025 ASCP Ventura-1/2 Poster; 12

company reports

Pramipexole off-label use in depression is limited by slow titration and significant dose-limiting nausea and vomiting

Clear dose-related nausea/vomiting prohibit achieving effective dose-levels of pramipexole FDA label requires slow titration in attempt to mitigate nausea

Real-world (EMR-linked AllofUs N=633,547) prescribing data demonstrate pramipexole dose escalation is done more slowly than approved titration schedule*

MDD

% of patients increasing dose slower than label- guided titration schedule

78%

70%

% of patients requiring a dose reduction

< 14 days following a dose escalation

16%

30%

Mean maximum daily dose achieved (mg)

0.71

1.38

Mean days to reach 1mg

658

592

PBO-Adj. Nausea PBO-Adj. Vomiting Total Dropout

70%

60%

50%

55%

58%

40%

30%

25%

34%

26%

30%

20%

10%

1mg (target)

Corrigan et al.

5mg (target)

Corrigan et al.

17%

2.3mg (mean)

Browning et al.

Average max doses are low

The vast majority of patients are titrated much slower than the label (quantified as % >1.5x slower)

Even with extremely slow titration, intolerance is substantial (i.e. de-escalation <14d after escalation)

* Only patients with >1 dose levels included (single dose averages: 0.24 [MDD] -0.5 [PD]). 13

PD = Parkinson's disease

ALTO-207 combination approach achieved higher pramipexole doses faster and more consistently

≥2.5x increase in pramipexole tolerability*

Until ALTO-207, all pramipexole depression trials followed the FDA-approved titration schedule

Proportion tolerating dose (%)

100

pramipexole

ALTO-207

0 2 4 6

Pramipexole daily dose (mg)

6 Nearly 2x higher dose achieved vs. PAX-D

Maximum tolerated dose (mg)

4 4.2mg

2.3mg PAX-D

avg. dose with 28-day titration

1.7mg

pramipexole ALTO-207

Total daily pramipexole dose (mg)

ALTO-207 enabled >5x faster

dosing and to a higher target

2 FDA label

PAX-D

Cusin

1 Corrigan 1mg

Chase Ph 1

Chase Ph 2a

Achieved a ≥2.5-fold higher max dose vs. pramipexole alone, titrated at

5x the FDA-approved schedule for pramipexole

60% of patients tolerated max dose of ALTO-207 (6mg pramipexole), in 12 days

0 10 20 30 40

Day

*Chase Therapeutics sponsored trial 14

ALTO-207 Phase 2a results are consistent with the robust antidepressant effects reported for pramipexole in the literature, with improved tolerability

Phase 2a: MDD randomized, placebo-controlled trial (N=32)*

Rapid titration to avg of 4.1mg/d pramipexole in 8 days (together with 16mg ondansetron) - 5x faster than pramipexole label

Moderate-severe MDD (baseline MADRS ALTO-207: 28.8; placebo: 28.2)

ALTO-207 demonstrated significantly greater reduction

in depressive symptoms compared to placebo

ALTO-207 demonstrated significantly greater

reduction in illness severity compared to placebo

Week 8 MADRS

∆ = 8.2 pts

*Chase Therapeutics sponsored trial

ALTO-207 (n=16)

Placebo (n=16)

ALTO-207 (n=16)

Placebo (n=16)

Phase 2a trial of ALTO-207 in MDD confirmed favorable safety and tolerability profile

Nausea and vomiting were the most common AEs - all were mild to moderate

Post-titration AEs*

ALTO-207 (N=13)

Placebo (N=15)

Unrelated

Nausea

2 (15%)

0 (0%)

2 (13%)

Vomiting

1 (8%)

3 (23%)

0 (0%)

2 (13%)

Headache

1 (8%)

0 (0%)

Sleepiness

0 (0%)

Titration AEs are related to Chase's maximum tolerated dose-based titration schedule, which Alto aims to further optimize in planned future trials

*Chase Therapeutics sponsored trial 16

ALTO-207 Phase 2b design - topline data 2H 2027

Adjunctive to an existing antidepressant with an insufficient response, mirroring PAX-D

Screening Period 8-Week Double-Blind Treatment

Period Including Titration

Key inclusion/exclusion criteria:

TRD with 2-5 treatment failures

On stable antidepressants with insufficient response (which continues unchanged)

No antipsychotics allowed

MADRS ≥ 25

Sponsor eligibility review with medical C pharmacy records required, urine antidepressant testing

Exclude impulse control disorders

U.S. and UK (PAX-D) sites

Placebo

3.2mg pramipexole/ 15mg ondansetron*

1:1 Randomization

N=178

PRIMARY OUTCOME: MADRS change from baseline

Total pramipexole dose selected to optimize efficacy and limit side effects based on PAX-D, Chase, clinical practice

Proprietary modified release formulation better PK-matches ondansetron (shorter half-life) to pramipexole

Custom titration schedule to top dose by day 13

Starter pack to make titration straightforward and mirror ultimate commercial approach

Central raters to reduce variability, with interview monitoring by Alto's proprietary LLM-based MADRS scoring system

* Total daily dose divided twice daily (BID) 17

Novel ALTO-207 product attributes and substantial patient risk deters off-label generic substitution

Key attributes of ALTO-207 that mitigate likelihood of generic substitution

Strong IP portfolio covering formulation, use, and titration protects from generic combination entry

Simple dosing C titration regimen (starter pack)

Single pill for ease of administration

Clear evidence of effect of combined product, if approved

Commercial strategies can mitigate patient out-of-pocket

costs and improve access

Prescribing off-label generic components introduces substantial patient s prescriber risk

Complex regimen of generic pills with different timing and half-lives likely to lead to dosing errors C severe adverse events

Unproven dose levels with non-standard combinations

Lack of formulation consistency/quality

Off-label prescribing creates liability for physicians

Lack of payer coverage for off-label Rx

Real-world treatment demonstrates lack of generic substitution

Auvelity (combination of bupropion and

dextromethorphan) provides clear evidence that off-

label combination generic substitution does not impede significant commercial success

Recent success in psychiatry, and TRD specifically, strongly supports combination approach and novel mechanism

Innovation

Clinical Benefit Projected/Est.

Antagonistic combination to mitigate AEs in schizophrenia (SCZ)

Novel MoA in SZ with

Cohen's d > 0.5

Synergistic combination of two generic medications

Novel combination in MDD, but with similar effect size to existing Tx (d=0.35)

Intranasal ketamine spray -drug-device combo Approved in TRD

Approved in TRD but with similar effect size to antipsychotics

Recent combination analogs

demonstrate…

improved tolerability,

larger effect size,

more convenient dosing,

and novel MoA in disease…

can result in significant adoption by physicians and substantial

Peak Revenue* ~$6bn

~$4bn+*

~$4bn

commercial success

Karuna acquired for $14bn

based on Cobenfy alone

Axsome market cap ~ $11bn^

primarily based on Auvelity

Despite 2-hour monitoring requirement, controlled substance, substantial AEs, dissociation etc.

If clinical effects and tolerability profile remain consistent with observed data, we expect ALTO-207, as a novel combination with a differentiated mechanism in depression, has blockbuster potential

*Source: Bloomberg consensus estimates or company reports - Auvelity reflects depression portions 19

^Consensus and market cap data accessed May 12, 202c

Phase 2b development as adjunctive for MDD

Disclaimer

Alto Neuroscience Inc. published this content on May 13, 2026, and is solely responsible for the information contained herein. Distributed via Public Technologies (PUBT), unedited and unaltered, on May 13, 2026 at 13:03 UTC.