ADXS-HER2 Clinical Program

Advaxis is developing ADXS-HER2 to target human epidermal growth factor receptor 2 (HER2)-expressing cancers. HER2 is expressed in certain solid-tumor cancers, including some breast, gastric, and esophageal cancers and osteosarcoma. ADXS-HER2 has received orphan drug designation from the FDA and EMA for the treatment of osteosarcoma. In April 2016 ADXS-HER2 was granted Fast Track Designation by the FDA for treatment of patients with newly diagnosed, non-metastatic, surgically-resectable osteosarcoma.

ADXS-HER2 is being evaluated in a first-in-human Phase 1b dose-escalation clinical study for the treatment of patients with metastatic HER2-expressing solid tumors. The dose escalation portion of the study will investigate the safety and tolerability of ADXS-HER2 as a monotherapy in patients diagnosed with metastatic HER2-expressing solid tumors. Results from the study will be used to determine the future clinical development program of ADXS-HER2.

Advaxis plans to conduct a pivotal trial in pediatric osteosarcoma in collaboration with Children’s Oncology Group (COG).

HER2

Canine Osteosarcoma

Advaxis is developing ADXS-HER2 in both human and animal health, and has seen encouraging data in canine osteosarcoma, which is considered a model for human osteosarcoma. Advaxis has licensed ADXS-HER2 and three other immunotherapy constructs to Aratana Therapeutics, Inc. for the development of animal therapeutics.

Preliminary data have demonstrated ADXS-HER2, in combination with palliative radiation, delayed tumor progression and prolonged overall survival in pet dogs with treatment-naïve spontaneous canine osteosarcoma. Repeat doses of ADXS-HER2 were well tolerated with no systemic or cardiac toxicity.

Osteosarcoma as a Therapeutic Target

Osteosarcoma is the most common primary bone tumor in dogs, accounting for roughly 85 percent of tumors on the canine skeleton.1 More than 10,000 dogs per year (predominately middle- to older-aged dogs and larger breeds) are diagnosed with osteosarcoma in the United States.1,2

HER2 is expressed in approximately 40-60 percent of pediatric and canine osteosarcoma and in pulmonary metastatic disease, suggesting that immune targeting of HER2 might delay or eliminate metastatic disease.3,4 The hypothesis warrants investigation and will be tested in a pivotal pediatric osteosarcoma trial. HER2 expression is associated with more aggressive disease, increased risk of relapse and decreased overall survival.4

References

1 Mullins, M.N., Lana, S.E., Dernell, W.S., Ogilvie, G.K., Withrow, S.J., & Ehrhart, E.J. (2004). Cyclooxygenase-2 Expression in Canine Appendicular Osteosarcomas. J Vet Intern Med;18:859–865.

2 Modiano, J.F. (2010) Bone Cancer in Dogs–What is the State of Practice and New Research? Retrieved December 18, 2015 from http://www.modianolab.org/cancer/cancer_osteosarcoma.shtml.

3 McCleese, J.K., Bear, M.D., Fossey, S.L., Mihalek, R.M., Foley, K.P., Ying, W., Barsoum, J., & London, C.A. (2009). The novel HSP90 inhibitor STA-1474 exhibits biologic activity against osteosarcoma cell lines. International Journal of Cancer, 125:12, 2792-2801. Retrieved December 18, 2015 from: http://onlinelibrary.wiley.com/doi/10.1002/ijc.24660/full.

4 Zhou, H., Randall, R.L., Brothman, A.R., Maxwell, T., Coffin, C.M., & Goldsby R.E. (2003). Her-2/neu expression in osteosarcoma increases risk of lung metastasis and can be associated with gene amplification. Journal of Pediatric Hematology and Oncology, 25:, 27-32.