Charge. Channel. Change.

Selectively silencing activated sensory neurons via a
first-of-its-kind mechanism

Nocion is developing a new class of small molecules, nocions™, designed to selectively silence activated sensory neurons that drive disease in conditions such as cough, pain, itch, and neurogenic inflammation. Our platform is built on a simple but powerful insight: many chronic conditions are driven by hyperexcitable sensory neurons that continue to fire long after the original triggers have passed. By directly targeting how these neurons signal to the central nervous system rather than blocking upstream triggers or broadly suppressing the nervous system, Nocion aims to deliver precise, durable symptom control with disease modification, while maintaining a favorable safety profile.

Redefining sensory neuron modulation from upstream blockade to downstream signal control

Sensory neurons, or nociceptors, detect environmental and inflammatory stimuli through a variety of receptors and ion channels. When activated, these neurons generate action potentials that signal to the central nervous system and are perceived as cough, pain, or itch. Many existing approaches to treating these conditions attempt to:

  • Block a single receptor or channel, or
  • Broadly dampen neuronal activity, often at the cost of tolerability.

How nocions work

Designed to enter only activated sensory neurons
1

Stimulus activates sensory neurons

In disease states, airway, skin, or visceral sensory neurons become hypersensitive and are easily activated.
2

Large pore channels open

Activation opens large pore ion channels (LPCs) that allow sodium and calcium cations to enter the neuron. Entry of these positively charged ions elicits a generator potential that triggers the activation of voltage-gated sodium channels (Naᵥ channels).
3

Nocions selectively gain access

Nocions are positively charged small molecules designed to enter nociceptors only when LPCs are open.
4

Downstream sodium channel inhibition

Once inside, nocions inhibit Naᵥ channels that are required for action potential propagation – silencing the neuron from within.
5

Signal stops at the source

The abnormal signal does not reach the central nervous system, reducing symptoms such as cough, pain, or itch, and inhibiting neurogenic inflammation.

Key implication

Neurons without large pore channels (e.g. mechanoreceptors and motor neurons) are unaffected, preserving normal sensation and function.
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Why charge matters:

Selectivity, localization, and durability by design

The permanent positive charge of nocions is central to their behavior:

  • Selectivity: Entry is favored in activated sensory neurons, not resting sensory neurons or neurons which lack large pore channels
  • Localization: Charged molecules do not readily cross cell membranes or the blood–brain barrier
  • Low systemic exposure: Supports local delivery and minimizes off-target effects
  • Durability: Once inside activated neurons, nocions demonstrate prolonged residence, supporting sustained activity

Together, these features enable a therapeutic profile designed to balance potency with precision.

One core platform, multiple therapeutic opportunities

Nocion’s platform enables:

  • Multiple molecules optimized for different tissues and indications
  • Multiple delivery routes, including inhaled, dermal, and oral formulations
  • Multiple disease areas, including cough, pain, itch, gastrointestinal disorders, and inflammatory conditions

Each program is designed with:

  • A molecule tuned to the target tissue
  • A formulation matched to the route of delivery
  • A disease-specific development strategy
  • It’s own specific intellectual property
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