AR-67

Target: Recurrent Glioblastoma Multiforme (reGBM), Colorectal, Ovarian, Pancreatic Cancer and Non-Small Cell Lung Carcinoma (NSCLC)

third-generation, completely synthetic Camptothecin-based compound

Target: Recurrent Glioblastoma Multiforme (reGBM), Colorectal, Ovarian, Pancreatic Cancer and Non-Small Cell Lung Carcinoma (NSCLC)

Vivacitas’ lead development candidate (AR-67) is a third-generation, completely synthetic Camptothecin-based compound. Employing a proprietary synthesis method, AR-67 is a novel lipophilic compound which targets improved efficacy, tolerability, and stability.

New generation of treatment

AR-67 is a silatecan-based, 3rd generation camptothecin with chemical modifications that enhance blood stability and increase the likelihood of cell penetration.

Increased potency

AR-67 is highly lipophilic, meaning that it is readily taken up by the hydrophobic environment of cellular membranes, thus providing significant protection from the extracellular milieu where it would otherwise be broken down to its inactive form.

AR-67 has also demonstrated evidence of crossing the brain-blood barrier, in preclinical and Phase II clinical studies.

Creating a new path forward

AR-67 has shown promise in in vitro, Phase I, and Phase II studies for multiple tumor types and has demonstrated the potential for progression-free survival in patients with recurrent glioblastoma of 6-29 months while significantly reducing severe side effects normally associated with this drug class (e.g., grade 4 diarrhea).

Our Difference

  • Potential Increase in bioavailability
  • Potential for Increased potency
  • Suggestive efficacy signals in initial clinical studies
  • Potential improvement in side effect profile
  • Potential increase in purity
  • Potential for more consistent/reliable supply
  • Potential for reduced steps/time/cost to manufacture
  • Potential for Quality of life improvement
AR-67 has the potential to deliver the efficacy of Camptothecins with significantly less gastrointestinal and hematological toxicity than Irinotecan. That could be a game changer for patients with gastrointestinal cancers.
Dr. Gerard Blobe, MD, PhD.Duke University School of Medicine.
AR–67 is a next generation camptothecin optimized for fewer side effects and blood-brain-barrier penetration. In glioblastoma patients treated with AR-67 on a clinical trial at our center, we saw encouraging outcomes and tumor shrinkage. AR-67 was extremely well tolerated. I believe AR-67 represents a novel approach in treating this devastating disease.
Dr. Jai Grewal, MD.NSPC Brain and Spine Surgery, NY

References

1. Novel silatecan displays high lipophilicity, improved blood stability and potent
anticancer activity. Bom D, et al J Med Chem 2000; 43:3970-3980

2. Silatecan DB-67 is a novel DNA Topo-1 targeted radiation sensitizer: Chen AY. Mol
Cancer Ther 2005; 4(2): 317-24.

3. Phase I study publication: Arnold SM, et al. Clin Cancer Res. 2010;6:673-680

4. Phase II study publication (abstract): Kumthekar P, et al. SNO 2019. Poster ACTR-40,
published in Neuro-Oncology(https://academic.oup.com/neuro-oncology)

5. Ubiquitin-dependent Destruction of Topoisomerase I Is
Stimulated by the Antitumor Drug Camptothecin*, Desai et al. The Journal of Biological Chemistry, Vol. 272, No. 39, Issue of September 26, pp. 24159–24164, 1997.  https://www.jbc.org

6. Metabolic Pathways of the Camptothecin Analog AR-67, Horn et al. Drug Metabolism and Disposition, Vol. 39, No. 4, 37390/3672838, 2011. https://dmd.aspetjournals.org