Clinical Development

The Company currently has the following three products in clinical trials:

ALT-801: Altor’s long-term clinical objective is to develop ALT-801, a p53-specific scTCR/IL-2 fusion protein, as a targeted immunotherapeutic with better antitumor potency, a lower toxicity profile and more convenient dosing schedule compared to that of human recombinant IL-2. The Company has completed an open-label, dose-escalating Phase I/IIa clinical trial (Clinical Trials.gov Identifier: NCT00496860). Twenty-six patients with various metastatic, refractory malignancies were enrolled and infused with at least one dose of ALT-801. Data indicate that ALT-801 is well tolerated at the maximum tolerated dose level and exhibits clinical benefit to cancer patients with various advanced diseases with 40% of the patients having stable disease, several with tumor shrinkage and one complete response. This trial was partially supported by an Orphan Products Development Grant from the US FDA.

A Phase Ib/II trial (Clinical Trials.gov Identifier: NCT01029873) using ALT-801 in combination with cisplatin in patients with metastatic melanoma started enrolling patients in Q1-2010. The objectives of this trial are to further assess safety and antitumor activities of ALT-801+cisplatin therapy against melanoma.

Another Phase Ib/II trial (Clinical Trials.gov Identifier: NCT01326871) using ALT-801 in combination with cisplatin and gemcitibine in patients with locally advanced or metastatic urothelial cancer started enrolling patients in June 2011. The objectives of this trial are to further assess safety and antitumor activities of ALT-801+cisplatin+gemcitabine therapy against muscle-invasive or metastatic bladder cancer.

Additional Phase II clinical trials in other cancer indications including prostate, head & neck and renal cell carcinoma will follow. A $3 MM NCI-SBIR Bridge Grant awarded to Altor in September 2009 supports some of these Phase II clinical trials.

The Company also has an active IND for a clinical trial using ALT-801 in an adoptive cell therapy setting for treatment of cancer. This trial is in progress. The outcome of this study may provide a rapid preliminary assessment comparing antitumor efficacy of ALT-801-targeted cellular therapy verses non-targeted approaches.

ALT-801 Fact Sheet...

ALT-836 (a recombinant chimeric anti-tissue factor antibody): 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 an abundance of 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 a TF antagonist in 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.

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 is underway using a multi-dose regimen to further evaluate safety and efficacy of ALT-836. The trial is projected to conclude in early 2012. A Phase II SBIR competing renewal grant was awarded to Altor by the NIH/NHLBI in May 2011 and is funding the cost of 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 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 been initiated.

ALT-836 Fact Sheet...

Product Development

STAR™ Agents for Cancer

ALT-802: In addition to the clinical development of ALT-801, Altor is advancing its second STAR™ cancer product, ALT-802, a fusion of the p53-specific scTCR to the heavy chain constant domain of human IgG1, providing the Fc domain to invoke ADCC against p53+ cancer cells. In mouse xenograft models, this product shows good efficacy against NSCLC and synergistic anti-tumor activity when used in combination with cisplatin, the first-line, standard-of-care treatment for NSCLC. An IND submission is planned for 2011.

ALT-802 Fact Sheet...

ALT-804: This is a fusion of the p53-specific scTCR to the IL-15 super-agonist mutein complexed with IL-15Ra-Fc and is undergoing pre-clinical studies.

Nanoparticles: The p53-specific scTCR has also been linked to cytokine/drug-encapsulated nanoparticles. These nanoparticles show considerable activity in animal models at a level substantially lower that the current therapeutic dose.

Cancer Therapeutics – other (non-p53) targeted agents: Altor has several additional non-p53 scTCRs targeting tumor-associated antigens, including MAGE A3, gp100 and MART-1. The scTCRs have been generated, enhanced for affinity, configured into various formats and have entered pre-clinical evaluation.

STAR™ Fusion Agents for Viral Infections

Altor is developing a large portfolio of human-derived STAR™ molecules against viral antigens from HIV, hepatitis C (HCV), and cytomegalovirus (CMV). These STAR™ molecules are being engineered into various formats as fusion proteins and drug or radioisotope conjugates to deliver viral therapies to diseased tissues. The Company intends to continue preclinical development of these STAR™ molecules and seek partnership opportunities for these and other targets.

Altor Antiviral TCR Platform...

IL-15 Super Agonists/Antagonists

ALT-803 an IL-15 super agonist complex between an IL-15 mutein and an IL-15Ra-Fc fusion protein. The IL-15 super-agonist mutein is proprietary to Altor and exhibits 4-5x higher activity compared to wild type IL-15. Plans are to develop this complex for treatment of solid and hematological malignancies. The complex is in cGMP manufacturing process and Altor is targeting early 2012 for IND submission. Wild-type IL-15 is currently the top priority for NIH/NCI as an anti-cancer therapeutic.

Antagonists: Altor has also isolated potent IL-15 antagonists as potential, new class agents for treatment of systemic inflammations and autoimmune diseases.

Adjuvant: The IL-15 super-agonist mutein is also available for licensing as a vaccine adjuvant.

Altor IL-15 Platform...

STAR™ Multimers Reagents

Altor has launched an exciting new class of innovative products based on its proprietary STAR™ technology. These products enable the detection of novel disease targets presented on the surface of cells and tissues. Altor continues to expand the reagent product portfolio.

Research Reagents...

Literature and Publications...

Back

© Altor BioScience Corporation, 2011