GRK2-biased β₂-adrenergic modulators

Where muscle
becomes medicinefor muscle wasting

First-in-class oral compounds that switch on muscle's metabolic machinery without the signaling liabilities that have blocked conventional β₂-drugs for nearly six decades.

Class 1 / 5Balanced full agonist
β₂AR signaling profile · isoprenaline
Subjects dosed
Phase I complete, CV safety confirmed
Mechanism published
Motso et al., 2025
Granted patents
Thousands of compounds
Oral, once daily
Phase II-ready
Why muscle matters

Muscle is at the centre of health.

Muscle does far more than move us. It shapes metabolic, skeletal, immune and cognitive health, and our capacity to recover.

higher risk of death from any cause for every 5 kg lower grip strength. It predicted death better than systolic blood pressure.

PURE study, 139,691 adults in 17 countries · Leong DP et al. Lancet 2015
Muscle
Metabolic healthGlucose control and obesity risk
LongevityAll-cause mortality risk
IndependenceDaily activities and care burden
Immune resilienceReserve through illness and surgery
Cognition & moodNeuromuscular cross-talk
Recovery capacityResilience after illness and disuse
Bone healthLoading sustains bone density
Mobility & fallsBalance, gait and fall risk
The problem

Muscle is being lost. And power goes first.

The incretin era

Weight loss on GLP-1 therapy includes muscle loss.

of the weight lost on semaglutide is lean mass

Highest risk: low muscle reserveOlder adults and people with sarcopenic obesity have least to lose.
Function is the real endpointWhether lean loss harms function is debated, so strength and power, not mass alone, must be protected.
What the weight lost is made of
Share of total weight lost, DXA body-composition substudies (approx.)
Lean massFat mass
What the weight lost is made of
Lean mass (%)Fat mass (%)
Semaglutide 2.4 mg (STEP 1)4060
Tirzepatide (SURMOUNT-1)2575
Wilding NEJM 2021 (STEP 1) · Look Diabetes Obes Metab 2025 (SURMOUNT-1) · Conte, Hall, Klein JAMA 2024 · Prokopidis J Nutr Health Aging 2025
Sarcopenia

Sarcopenia is common, and it raises the odds of death.

of adults aged 60 and over have sarcopenia

Up to 51% in nursing homesVersus 9–11% of older adults living at home. Pooled from 41 studies.
~1% of muscle mass a yearLost in later life, while strength falls 2–5× faster.
Pooled odds ratio vs. people without sarcopenia
1.0× = no difference
Pooled odds ratio vs. people without sarcopenia
Pooled odds ratio vs. people without sarcopenia
Mortality3.6×
Functional decline3.0×
Falls1.9×
Fractures1.7×
Petermann-Rocha 2022 · Papadopoulou 2020 · Mitchell 2012 · Beaudart PLoS One 2017 · Yeung 2019
Powerpenia

Power fails first, and fastest.

of leg power lost each year in healthy adults aged 65–89, from a decline that starts around 40

  1. 01Power declines
  2. 02Strength and mobility fall
  3. 03Falls, frailty, dependence
  4. 04Morbidity and mortality rise
Estimated annual decline in later life
% per year
Estimated annual decline in later life
Annual decline
Muscle mass1.0%
Muscle strength1.5%
Muscle power3.5%

Low power carries 5.9–6.9× the mortality risk; low strength 1.6–1.7× (CLINIMEX, n = 3,889).

Skelton 1994 · Mitchell 2012 · Alcazar 2020 · Araújo Mayo Clin Proc 2025. Rates vary by study and age; in each, power falls fastest.

Protecting muscle power helps protect life.

Our answer

Eight pathways. We keep two.

Classical β₂ agonists switch on every pathway, including the ones that strain the heart and wear the receptor out. The Atrogi class keeps glucose uptake and GRK2 and leaves the rest near zero.

Atrogi classIsoprenaline
Glucose UptakeGRK2cAMPGsInternalizationβ-Arrestin2Ca²⁺G15
Mechanism

Fuels muscle. Builds muscle.

Like exercise, one GRK2-biased signal does both. It drives glucose into muscle without insulin, and it preserves and builds muscle mass in preclinical models.

ATR-258
Oral ligand
β₂AR
GRK2-biased binding
GRK2
Non-canonical complex
mTORC2
Signaling hub
GLUT4
Glucose uptake, without insulin
Muscle mass ↑
Preserved and built in preclinical models
Pipeline

Four programs. One platform.

ATR-258
Skeletal Muscle Health, Sarcopenia
DiscoveryPreclinicalPhase IPhase IIPhase III
Next: ATTRACTIVE 3 proof-of-concept
ATR-258
Obesity / GLP-1 Add-on
DiscoveryPreclinicalPhase IPhase IIPhase III
Next: ATTRACTIVE 4
ATR-339
Obesity
DiscoveryPreclinicalPhase IPhase IIPhase III
Next: Toxicology studies
Next-Gen
Muscle Wasting, DMD, FSHD
DiscoveryPreclinicalPhase IPhase IIPhase III
Investors and partners

Phase II-ready.
Let's talk.