Aprea’s first-in-class lead candidate drug APR-246 reactivates the tumor suppressor protein p53 which is deficient in around 50% of all human tumors, mainly due to mutations of its DNA-binding domain. The mutations result in loss of p53-dependent cell cycle arrest and apoptosis which is an important growth control mechanism that protects against tumor growth. In addition, mutations in p53 or its regulators are associated with increased resistance to standard chemotherapy and hence poor prognosis.
Aprea’s Phase Ib/II PiSARRO trial investigates the safety and efficacy of APR-246 in combination with carboplatin and doxorubicin in second-line treatment of patients with high grade serous ovarian cancer. The poster presented at the AACR Annual Meeting shows preliminary results for the first dosing cohort with three patients in the Phase Ib part of the study.
“The data on the first three patients in the PiSARRO study indicates that APR-246 can be used in this combination regimen for the intended patient group and we have not seen any new safety concerns. Also, early indications of activity have been observed with partial RECIST responses from all three patients. However, while these data are encouraging, we are also careful not to draw any conclusions from these first patients in the dose escalation part of the study that does not have a control arm. We are now awaiting the full Phase Ib results,” comments Ulf Björklund, CEO of Aprea.
In addition, Aprea will also present two posters today at the AACR Annual Meeting with preclinical data of APR-246, showing strong synergistic response with APR-246 and chemotherapy in ex vivo cancer cells from ovarian cancer and lung cancer cells respectively. The two posters regarding ovarian cancer are attached to this press release. Upon its presentation later today (Eastern Daylight Time) at the AACR Annual Meeting, the lung cancer poster will be available on Aprea’s website (www.aprea.com) together with the other two posters presented at the conference.
For further information, please contact:
Ulf Björklund, CEO, Aprea AB
Phone: +46 (0) 8 508 845 04, e-mail: ulf.bjorklund@aprea.com
Jim Van heusden, CEO, Karolinska Development AB
Phone: +46 (0) 72 245 9892, e-mail: jim.van.heusden@karolinskadevelopment.com
TO THE EDITORS
About Aprea AB
Aprea AB is a Swedish biotech company focusing on discovery and development of novel anticancer compounds targeting the tumor suppressor protein p53. The main owner of Aprea is KDev Investments AB, part of Karolinska Development AB (publ). The other main owners are Östersjöstiftelsen, Praktikerinvest and KCIF Co-Investment Fund KB. For more information, please visit www.aprea.com
About APR-246
APR-246 has been developed based on results from researchers at Karolinska Institutet, and has been shown to reactivate non-functional tumor suppressor protein p53 and induce programmed cell death in many human cancer cells. Preclinical studies have confirmed that APR-246 can activate mutated p53 and demonstrated single agent efficacy and very strong synergy with conventional anti-cancer agents in vitro and in vivo. A clinical Phase Ib/II study in hematological malignancies and prostate cancer has been completed, demonstrating a favorable safety profile and both biological and clinical responses. A Phase Ib/II proof-of-concept study in ovarian cancer patients carrying mutant p53 is currently ongoing.
About the PiSARRO trial
The Phase Ib/II trial is designed to evaluate the safety, efficacy, pharmacokinetics and pharmacodynamics of APR-246 in combination with carboplatin (AUC 5) and pegylated doxorubicin (30 mg/m2), a second line standard of care chemotherapy for relapsed platinum sensitive high grade serous ovarian cancer. The Phase Ib/II trial is a two-part study that will enroll approximately 180 patients. Part A is an open-label, multiple ascending dose study. The primary objectives of Phase Ib are to evaluate the safety and tolerability of APR-246 in combination with carboplatin and pegylated doxorubicin, and to confirm the dose of APR-246. Pending successful completion of this phase, Aprea expects to initiate Part B of the trial, which will be a randomized, controlled study investigating the safety and antitumor activity of APR-246 administered in combination with carboplatin and pegylated doxorubicin, compared with carboplatin and pegylated doxorubicin alone. Primary end point of Phase II will be Progression Free Survival (PFS). For details on the PiSARRO trial please visit: www.ClinicalTrials.gov.
About Karolinska Development AB
Karolinska Development aims to create value for patients, researchers, investors and society by developing innovations from world class science into differentiated products that can be partnered. The business model is to: SELECT the most commercially attractive medical innovations that can potentially satisfy unmet medical needs; DEVELOP innovations to the stage where the greatest return on investment can be achieved; and COMMERCIALIZE the innovations through the sale of companies or out-licensing of products. An exclusive deal flow agreement with Karolinska Institutet Innovations AB, along with other cooperation agreements with leading universities, delivers a continuous flow of innovations. For more information, please visit www.karolinskadevelopment.com.
Karolinska Development is listed on NASDAQ OMX (KDEV). Karolinska Development may be required to disclose the information provided herein pursuant to the Securities Markets Act.
