Aprea presents preliminary clinical Phase Ib/II results in ovarian cancer with APR-246 – a 'first-in-class' compound reconverting mutant to wild-type p53 protein

STOCKHOLM – October 23, 2015. Aprea AB, a Karolinska Development AB (Nasdaq Stockholm: KDEV) portfolio company, announces updated preliminary data from its ongoing Phase Ib/II clinical study in collaboration with The European Network for Translational Research in Ovarian Cancer (EUTROC).  The data will be presented on Saturday, October 24, at the European Society of Gynaecological Oncology (ESGO) International Meeting in Nice, France and reinforces the indicative conclusions presented from the study on April 20, 2015; that APR-246 can be combined with standard of care chemotherapy and that preliminary efficacy data of the combination regimen show activity in treatment of recurrent ovarian cancer.

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. Today, preliminary results for the first 24 patients in the Phase Ib part of the study are announced of which 8 patients have completed all 6 cycles of combination therapy with APR-246.

At cut-off, all patients treated in the study have stable disease or better according to RECIST criteria. In addition, 13 out of 14 evaluable patients have GCIG CA-125 (tumor antigen biomarker) response after 3 treatment cycles. Hence the preliminary efficacy data indicate that APR-246 in combination with chemotherapy has activity in patients with partially platinum sensitive as well as patients with platinum sensitive disease.

APR-246 showed linear pharmacokinetics with no accumulation and low intra patient variability and no indication of interaction between APR-246 and chemotherapy was seen. This indicates that APR-246 can be combined with carboplatin and doxorubicin at relevant doses.

No new safety concerns have emerged in the study. The main treatment-emergent adverse events have been low grade gastrointestinal and central nervous system related events. One dose limiting toxicity (DLT) of ruptured diverticulum occurred at the second dose level leading to expansion of this cohort to 6 patients. A possible increase in hematological side effects over those expected with the chemotherapy alone cannot be ruled out at this stage.

Mikael von Euler, CMO of Aprea comments: "We continue to be encouraged by the preliminary results emerging from the Phase Ib part of the study. Firstly, the safety and pharmacokinetic data indicate that APR-246 can be combined with chemotherapy at full dose in the ovarian cancer setting. Secondly, the early efficacy data from the evaluable patients indicate that the combination regimen with APR-246 has activity in ovarian cancer patients that are either partially or platinum sensitive. While we are careful not to draw definite conclusions from these preliminary results, we are encouraged by the data indicating that APR-246 has the potential to improve treatment for ovarian cancer patients."

The poster Preliminary Results from EUTROC PiSARRO: a Phase Ib Study Combining APR-246 with Standard Chemotherapy in Platinum Sensitive Relapsed High Grade Serous Ovarian Carcinoma (HGSOC) will be presented at the ESGO on Saturday, October 24, in an e-poster session that will start at 07.00 CEST and the poster is also attached to this press release and available at Aprea's website www.aprea.com

Download poster

For further information, please contact:
Ulf Björklund, CEO, Aprea AB
Phone: +46 (0) 8 508 845 04, e-mail: [email protected]

Jim Van heusden, CEO, Karolinska Development AB
Phone: +46 (0) 72 858 32 09, e-mail: [email protected]



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 Professor Klas Wiman and colleagues 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.

The European Network for Translational Research in Ovarian Cancer (EUTROC) was established to improve the current and future management in ovarian cancer and to bring the complex matrix into a single multidisciplinary, transnational framework for ovarian cancer. EUTROC aims to define and give direction to the clinical, scientific, and technological unmet needs by performing activities such as a European-wide tumour bank and technological platforms which will provide a roadmap for the identification and prioritisation of suitable biomarkers. EUTROC's network includes institutions with broad experience in clinical and scientific work in ovarian cancer that are dedicated to improving the long-term clinical outcome of patients within an integrated collaboration across Europe.

About Karolinska Development AB
Karolinska Development AB is an investment company focused on identifying medical innovation and investing in the creation and growth of companies developing these assets into differentiated products that will make a difference to patients' lives and provide an attractive return on investment.

Karolinska Development has access to world-class medical innovations at the Karolinska Institutet and other leading universities and research institutes in the Nordic region. The Company aims to build companies around scientists who are leaders in their fields, supported by experienced management teams and advisers, and co-funded by specialist international investors, to provide the greatest chance of success.

Karolinska Development has established a portfolio of 12 companies targeting opportunities in innovative treatment for life-threatening or serious debilitating diseases.

The Company is led by a team including investment professionals with strong venture capital backgrounds, experienced company builders and entrepreneurs, with access to a strong global network.

For more information, please visit www.karolinskadevelopment.com