PIPELINE

Researchers at OncoArendi study the therapeutic potential of chitinases and chitinase-like-proteins (CLPs) which provide multiple points for therapeutic intervention. OncoArendi currently has a platform of 3 distinct small molecule programs targeting chitinases and CLPs, with potential utility in diverse inflammatory and fibrotic diseases of high unmet medical need.

Further to that, and in close collaboration with several leading academic and clinical institutions and industrial partners, OncoArendi has initiated a program focused on development of small molecule immune-modulators to knock down the ability of tumors to escape immune surveillance.  These unique, proprietary compounds will target a strategic enzyme involved in amino-acid metabolism that allows tumor cells to hamper antitumor immunity and to avoid immune surveillance.

 

 

 

 

OATD-01

Asthma is a chronic inflammatory disease that affects approximately 300 million people worldwide. Despite the availability of bronchodilators and anti-inflammatory drugs, asthma remains an unmet medical need due to complex patient stratification challenges with significant groups demonstrating resistance to current treatments (along with their side effects) and poor patients’ compliance to inhaled drugs.

There is a compelling preclinical and clinical evidence indicating that chitinase family of hydrolases, which includes two enzymes degrading chitin found in humans - acidic mammalian chitinase (AMCase) as well as chitotriosidase-1 (CHIT1) - contribute to the Th2-driven inflammatory responses as well as tissue injury and remodeling associated with asthma.

AMCase has been shown to be produced during inflammatory diseases in several organs. Its increased levels and activity were reported in airway inflammation induced by both chitin-containing (HDM) and chitin-free (papain, ovalbumin) allergens in mice. Humans suffering from allergic diseases, including asthma, have been shown to produce increased amounts of AMCase.

The second enzymatically active protein - CHIT1 is involved in development of lung fibrosis. Patients with interstitial lung diseases have increased CHIT1 activity that correlates with disease severity.

Accumulating evidence indicates that both enzymes are involved in the regulation of pulmonary inflammation and fibrosis-associated airway remodeling during asthma making them attractive therapeutic targets for novel drugs.

Following rational design and synthesis of well over 1000 compounds, OncoArendi has developed a first-in-class therapeutic product for asthma treatment, the clinical candidate OATD-01.

OATD-01 is the first chitinase inhibitor to have entered formal pre-clinical development.

OATD-01 has certain unique features:

  • Novel, efficacious and safe, non-steroidal small molecule inhibitor strategy to treat asthma by targeting the key mechanistic pathways involved in airway inflammation
  • Dual anti-inflammatory and anti-fibrotic activity through inhibiting chitinases with a single NCE in the in vivo model of airway inflammation induced by house dust mite
  • Oral delivery significantly improving patient compliance, once-a-day dosing (supported by animal PK studies in three species)
  • Proprietary IP (two US patents granted, three pending in national validation & PCT phase)

Program is currently at clinical development stage.

CHIT-1 selective inhibitor

Idiopathic pulmonary fibrosis is a fatal and progressive interstitial pneumonia. The disease is characterized by altered cellular composition and activity leading to excessive accumulation of extracellular matrix and loss of lung function. The mortality in IPF within the first 5 years after diagnosis is 50%. No effective treatment exists for the disease, making it a pressing unmet medical need.

Serum chitotriosidase 1 (CHIT1) has been identified as a potential marker of interstitial lung diseases characterized by inflammation and tissue remodeling, including IPF. The increased CHIT1 activity in the bronchoalveolar fluid (BALf) of patients with IPF and in vivo data from studies using transgenic animals indicate that the enzyme is involved in fibrogenesis.

Enabled by crystallography data for key proteins, OncoArendi team designed several highly potent and selective inhibitors. The program is currently at the advanced lead optimization stage.

 

 

OncoArendi Laboratorium

 

 

 

OncoArendi Laboratorium

YKL-40 Program

Development of the YKL-40 antagonist represents an entirely new approach to treat glioblastoma multiforme (GBM) and other cancers. YKL-40 is one of the most differentially expressed proteins in GBM and has been shown to mediate GBM tumorigenesis in multiple ways including increased angiogenesis, tumor cell invasiveness and proliferation. Additionally, it facilitates formation of the tumor-promoting, immunosuppressive environment.
Although YKL-40 belongs to the family of chitinases, it does not have an enzymatic activity and instead functions as a growth factor/cytokine promoting tumorigenesis by binding to receptors and modulating multiple signaling pathways. Two YKL-40 receptors, IL13Ra2 and syndecan-1 are highly expressed in GBM where they promote tumor growth, invasiveness and angiogenesis.
 Almost all targeted therapies involving small molecules rely on inhibition of the enzymatic activity of proteins implicated in tumorigenesis, limiting a number of potentially drugable targets. Successful identification of the YKL-40 inhibitor will confirm a feasibility of targeting a cytokine-like protein and will pave a way for the development of novel small molecule inhibitors for the non-enzymatic targets.
Several compounds with high affinity have already been identified. Structural information on several compounds co-crystallized with YKL-40 is helping to accelerate the hit-to-lead progression.

 

Arginase inhibitor program

Cancer immunotherapy is quickly becoming a major component of combination treatment schedules for patients with multiple types of cancer. Check-point inhibitor-based cancer immunotherapies have shown spectacular antitumor effects, but are effective in less than 30% of cancer patients. Therefore, there is a need to develop alternative therapeutic strategies to activate additional pathways for combination immunotherapies.

OncoArendi program in immuno-oncology is focused on developing small molecule inhibitors of arginases – enzymes involved in L-arginine degradation that generate immunosuppressive microenvironment.

In the absence of L-arginine T lymphocytes cannot be activated due to decreased levels of components of the antigen recognition system.

OncoArendi has discovered a new class of very potent, orally active arginase inhibitors that reverse arginase-mediated T lymphocyte suppression, and show antitumor effects in multiple tumors growing in immunocompetent syngeneic mice. Tumor growth inhibition (TGI) is accompanied by increased L-arginine concentration and robust proliferation of antigen-specific T lymphocytes. It is expected that arginase inhibitors can be combined with other immunotherapeutic approaches including check-point inhibitors, IDO inhibitors or cancer vaccines.

Our compound OATD-02 has been selected as a clinical candidate and has entered formal pre)clinical development in June 2017.

 

 

 

OncoArendi LAboratory

 

Myoglobin

New Exploratory Programs

To ensure a continuous flow of suitable candidate molecules into our development pipeline, we regularly initiate new exploratory drug discovery programs based on the existing targets that will complement or reinforce our pipeline and use our in-house expertise. We are looking for first-in-class or best-in-class opportunities that address diseases of unmet medical need.

DISCOVERY PARTNERSHIPS

OncoArendi Therapeutics has weaved a tight network of collaboration with various world renowned institutions of which:

  • Medical University of Warsaw, Poland
  • Cedars-Sinai Medical Center, CA, USA
  • Rutgers University, NJ, USA
  • Yale University, New Haven, CT, USA
  • Brown University, Providence, RI, USA
  • Nencki Institute of Experimental Biology of the Polish Academy of Sciences, Warsaw, Poland
  • Institute of Biochemistry and Biophysics of the Polish Academy of Sciences, Warsaw, Poland
  • International Institute of Molecular and Cell Biology, Warsaw, Poland
  • University of Oxford, Oxford, UK
  • Flanders Institute for Biotechnology (VIB) / Ghent University, Belgium
  • University of Warsaw, Poland
  • Nanovelos, Warsaw, Poland
  • Scanmed SA, St. Rafael Hospital, Cracow, Poland

OncoArendi is interested in establishing new alliances and partnerships early in the drug development process to leverage its core competencies.

 

 

GRANTS

OncoArendi Therapeutics has weaved a tight network of collaboration with various world renowned institutions of which:

  • POIR.01.01.01-00-0168/15 - Badania przedkliniczne i kliniczne kandydata na innowacyjny lek w terapii astmy i nieswoistych chorób zapalnych jelit
  • POIR.01.01.01-00-0551/15 - Opracowanie kandydata na lek „first-in-class” w terapii idiopatycznego włóknienia płuc w oparciu o substancje czynne blokujące chitotriozydazę
  • POIR.01.01.01-00-0552/16 - Opracowanie kandydata na lek ‘first-in-class’ w terapii przeciwnowotworowej w oparciu o substancje czynne blokujące YKL-40
  • STRATEGMED2/265503/3/NCBR/15 - Opracowanie nowych terapii opartych na stymulacji przeciwnowotworowego działania układu odpornościowego
  • PBS3/A8/36/2015 - Inhibitory MMP-9 jako nowy lek blokujący rozwój padaczki
  • 686089 - Scaling-up biodegradable nanomedicines for multimodal for multimodal precision cancer immunotherapy (PRECIOUS)

 

Finished projects:

 

BUSINESS DEVELOPMENT

Our success lies in our unique ability to identify novel targets across different therapeutic areas and our talent in progressing compounds with novel modes of action quickly through preclinical development up to clinical proof of concept.

OncoArendi is interested in establishing new alliances and partnerships early in the drug development process to leverage its core competencies: identifying novel targets, expanding understanding of the biology of diseases and developing therapeutics with novel modes of action that impact patient care. OncoArendi is planning to advance its programs up to Phase II clinical trials, and intends to out-license or otherwise partner late preclinical and clinical phase drug candidates.