# Using in-vivo Real-time Biosensor to Evaluate Prodrugs Designed to Prolong Therapeutic Effects for Smoking Cessation.

> **NIH NIH R41** · SPACERX LLC · 2024 · $55,000

## Abstract

Abstract
We propose to iden0fy an op0mal smoking cessa0on drug candidate by monitoring how our newly synthesized
varenicline prodrugs alter real-0me brain dopamine responses to nico0ne. Varenicline (CHANTIX®) is currently the
leading FDA-approved oral medica0on for smoking cessa0on. However, only 22% of pa0ents maintain abs0nence for 52
weeks aNer varenicline treatment. Addi0onally, more than 67% of pa0ents prematurely discon0nue treatment,
indica0ng a need for therapies that improve pa0ent compliance. To address this, we have developed extended-release
prodrugs that aim to enhance the pharmacokine0c proper0es of varenicline. Varenicline works by reducing nico0ne
craving and use by increasing dopamine levels transiently and then blocking the dopamine response to nico0ne. These
changes stabilize dopamine signaling in the brain, reducing the side effects of temporary dopamine increases and
prolonging the drug's ability to reduce the reward value of nico0ne.
In our STTR Phase I grant, we will use an in vivo dopamine biosensor to evaluate real-0me dopamine levels in the
striatum aNer administering our novel prodrugs. We will establish a rela0onship between brain efficacy and drug levels in
vivo. These studies will allow us to screen for prodrugs that have op0mal efficacy in altering both the level and dura0on
of dopamine response, which serves as a biomarker for predic0ng the effec0veness of smoking cessa0on drugs. Our
ini0al pilot data show that, compared to varenicline, our prodrugs posi0vely alter the dopamine release profile in the
striatum.
As the developers of a novel drug for smoking cessa0on, we are seeking mentorship to gain a beZer understanding of
the market forces that will determine the success or failure of our approach to this significant health challenge. The I-
Corps™ program will guide and enable us to reach out to relevant stakeholders, such as prospec0ve pa0ents, physicians,
insurers, regulators, and pharmaceu0cal companies. Through this effort, we aim to iden0fy the unique value proposi0on
that sets our product apart from exis0ng solu0ons and use this knowledge to develop a robust strategy for our
commercializa0on plan in a subsequent SBIR Phase 2 grant.

## Key facts

- **NIH application ID:** 10987756
- **Project number:** 3R41DA056334-01A1S1
- **Recipient organization:** SPACERX LLC
- **Principal Investigator:** John Nicholas Betley
- **Activity code:** R41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $55,000
- **Award type:** 3
- **Project period:** 2024-02-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10987756

## Citation

> US National Institutes of Health, RePORTER application 10987756, Using in-vivo Real-time Biosensor to Evaluate Prodrugs Designed to Prolong Therapeutic Effects for Smoking Cessation. (3R41DA056334-01A1S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10987756. Licensed CC0.

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