Aprea AB

Aprea AB 

Aprea develops drugs for the treatment of cancer by induction of apoptosis. The company focuses on bringing compounds through the stages from pre-clinical development to proof of concept in man.

Its primary drug candidate APR-246 is a small molecule anticancer drug which belongs to a new chemical class, which is protected by a thorough patent portfolio. It originates from research at the world-class medical institute Karolinska Institutet (KI) in Sweden. APR-246 has been shown to induce apoptosis (programmed cell death) through the tumor suppressor protein p53 – “the guardian of the genome” and has potential applications in a broad spectrum of cancer indications.

Resistance to existing therapies is one of the major obstacles in curing cancer. APR-246 has unique features as it has shown to induce apoptosis in cancer cells with mutated or otherwise dysfunctional wild type p53, i.e. in cancer cells that are often resistant to conventional therapies. Thus, APR-246 targets “difficult-to-treat” cancer cells over normal cells and, importantly, also shows additive or synergistic effects with conventional chemotherapy. A Phase I/II dose-escalating safety study with APR-246 has recently been completed. A continuation of the study was recently started with the aim to further evaluate safety, pharmacokinetics and to establish the optimum dose and duration of exposure.

The Company currently devotes its resources to building value, first and foremost, in relation to its primary candidate drug APR-246, and secondarily through its oral analog project.

In addition, Aprea owns patent rights for a new drug target, WRAP53. The novel gene WRAP53 has been shown to be involved in cancer cell survival. Interesting recent data show a correlation between WRAP53 protein expression in head and neck cancer cells and survival of patients.

The Challenge

Cancers develop and spread due to the malfunction of the natural growth control mechanisms of cells. Mutations in the tumor suppressor protein p53 are common in many human cancers, and in cancers where the gene itself is not mutated the p53 pathway is often partially inactivated. The result is loss of both p53-dependent cell cycle arrest and apoptosis (programmed cell death).  

Aberrations in p53 or its regulators in cancer cells are also associated with increased resistance to standard chemotherapy and, hence, poor prognosis. Mutations of the p53 gene occur in around 50 percent of cancer tumors and can be found in almost all known human cancer indications. As such, p53 is a prime target for future first-line cancer therapies.   

The Solution 

Restoration of p53 function should eliminate tumor cells by apoptosis. Aprea has identified a new class of small molecules that induce apoptosis through a p53-mediated mode of action. APR-246 has been shown to reduce cell viability, and/or induce apoptosis, in many cancer cell lines with different p53 status.

An antitumor effect of APR-246 has also been shown in ex vivo studies on acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL) cells from patients with wild type or p53-mutated cancer cells. Moreover, in efficacy studies using various cancer cell lines and models, APR-246 has demonstrated a statistically significant anticancer effect.

In a Phase I/II dose-escalating study APR-246 was given as an intravenous two hour infusion to patients with advanced hematological or prostate malignancies. The highest feasible dose achieved was at a level indicating a high therapeutic index.

The back-up program of APR-246 focuses on orally active analogs. Several compounds demonstrating promising results have been identified.

Competitive Advantages 

Due to its unique pharmacological properties and mechanism of action, APR-246 has the potential to be active in a broad range of cancer indications.

• Induces apoptosis in p53 dysfunctional chemo-resistant cancer cells – offering the possibility to provide effective therapy even to patients who are resistant to conventional chemotherapy  
• Demonstrated cancer cell specificity in primary cells from patients, i.e. higher potency in suppressing growth of cancer cells over normal cells, compared to conventional cytostatics
• Synergistic or additive effects with different types of conventional chemotherapy observed in various cell lines and primary cells from patients
• High therapeutic index, based on preclinical as well as clinical studies  
• Promising therapy for combination treatment without adding to the burden of serious side effects associated with current chemotherapy regimens

The Market

Oncology is one of the fastest growing segments in the pharmaceutical market. The value of the market in terms of sales reached USD 70 billion in 2009. Several new cancer drugs have been launched in recent years and have been rapidly adopted. Their success in terms of sales, despite modest clinical benefits, indicates a huge unmet medical need. Improved treatment options to current standard therapy are in great demand.

Status

• A Phase I/II dose-escalating safety study in patients with refractory hematological malignancies or prostate carcinoma has been completed
• APR-246 demonstrated good tolerability in the clinical study with the possibility to administer potentially effective doses
• Continuation clinical study initiated
• Key patents for APR-246 and back-up analogs granted in the US and EU
• Investigational Medicinal Product of high quality and robust product properties has been achieved  

Planned Milestones

• Secure preclinical studies to support clinical Phase II design
• Initiate Phase II proof of concept study
• Secure funding for reaching proof of concept
• Select candidate drug with oral administration properties 

Patent Status

Aprea has filed applications covering six patent families, and have more than 70 granted patents. The patent portfolio provides the company with comprehensive protection of its commercial opportunities.  

Due to its unique pharmacological properties and mechanism of action, APR-246 has a potential to be active in a broad range of cancer indications.  

Updated in January, 2012