In February 2008, Altor entered into a license agreement with Genentech, Inc. for exclusive, worldwide rights to develop and commercialize a class of antibody-based Tissue Factor (“TF”) antagonists.
Inflammation: TF is a membrane protein that initiates the extrinsic coagulation pathway. There is abundant published evidence demonstrating crosstalk between coagulation and inflammation. Coagulation factors activate pro-inflammatory cells and elicit inflammatory responses, while pro-inflammatory cytokines induce TF expression that leads to activation of coagulation factors. In numerous research studies, TF antagonists, including ALT-836, were shown to effectively block coagulation and systemic inflammation. These results provided the foundation for Altor to explore the therapeutic potential of ALT-836in this field, ultimately leading to a Phase I/IIa clinical trial designed to evaluate ALT-836 in patients diagnosed with infection-induced acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), two forms of life-threatening, systemic inflammatory disease with a 40% morality rate. Infection-induced ALI/ARDS represents a major unmet medical need and provides an enormous market opportunity for any licensed therapeutic. The Phase I/IIa study was completed in 2006. The results indicated that ALT-836 exhibits biological activities at a well-tolerated level in this patient population (Morris, et al. 2012 BMC Pulm Med 12:5 - Pubmed Link).
In 2009, Altor initiated a multi-center, randomized, placebo-controlled Phase II clinical trial of ALT-836 in ALI/ARDS patients (Clinical Trials.gov Identifier: NCT00879606). Sixty patients have been enrolled and interim analysis indicates favorable safety and clinical benefits to patients receiving a single-dose of ALT-836.
A second Phase II, 90-patient trial using a multi-dose regimen to further evaluate safety and efficacy of ALT-836 has been completed. A $3 MM Phase II SBIR competing renewal grant was awarded to Altor by the NIH/NHLBI in May 2011 to support this multi-dose trial.
Cancer: TF is over-expressed by all types of cancers and plays pivotal roles in tumor growth, tumor metastasis and tumor angiogenesis. Clinical studies indicate that the amount of TF expressed by cancers is directly related to metastasis rates and indirectly related to survival. In addition, patients with cancer experience a significantly higher than expected incidence of venous thrombo-embolic disorders, commonly referred to as Trousseau’s syndrome. These complications, can be particularly life threatening during chemotherapy, are caused by TF expressed by cancer cells. Inhibition of TF has been shown to reduce tumor growth, metastasis and tumor-induced venous thrombo-embolic events in numerous animal models and represent a novel approach to anticancer therapy.
A Phase I/IIa clinical trial (Clinical Trials.gov Identifier: NCT01325558) to assess safety and antitumor activities of ALT-836 in combination with gemcitabine for locally advanced or metastatic solid tumors failing the standard of care treatment has been concluded. Preliminary results indicate that the treatment regimen provides substantial clinical benefits, including objective responses, to patients with certain cancers.
ALT-836 Fact Sheet (PDF)...