Pipeline

ACT Biotech is developing a portfolio of oral small molecule kinase inhibitors as anti-cancer drugs.

The pipeline includes drugs with mechanisms of action in several high-value areas such as signal transduction and anti-angiogenesis. The most advanced candidate, Telatinib, is on track for NDA/MAA filing in first line gastric cancer by 2014, having recently completed a phase 2 trial in previously untreated patients. The next candidate, ACTB1003, is a first in class inhibitor of both the PI3K pathway and all four FGF receptors that will enter Phase 1 clinical trials in 2011. Other pipeline products address specific unmet needs in both solid and hematological tumors.

Telatinib: Phase 3-ready anti-angiogenic for gastric and other solid tumors

ACT Biotech’s highly promising lead program is Telatinib, a selective, potent and orally available inhibitor of VEGFR, PDGFR and KIT tyrosine kinases. Telatinib is the most selective kinase inhibitor ever developed, based on the Ambit KINOMEscan screen (Ambit Biosciences, Inc.).

Telatinib hits only its intended receptors, thus eliminating off-target side effects. Telatinib is therefore well-tolerated at high, continuous doses and exhibits no overlapping toxicities with chemotherapy. As a result, Telatinib is both highly effective as a single agent, having shown confirmed tumor regressions in multiple tumor types, and is combinable at the full monotherapy dose level with chemotherapy, without adding toxicity. ACT Biotech believes that Telatinib’s unique ability to combine tolerably at full dose level with chemotherapy sets it apart from the competition in target indications. A Phase 2 trial in combination with standard-of-care chemotherapy in first-line gastric cancer was recently completed. Results will be presented in mid 2011. Based on the phase 2 results ACT Biotech is currently preparing for pivotal trials in first-line gastric cancer and is on track for NDA/MAA filing by 2014. Telatinib was previously studied in two Phase 1 monotherapy and four Phase 1b combination therapy trials in a total of over 250 patients. In those studies Telatinib showed strong efficacy signals, including monotherapy tumor regressions in five different solid tumor types, coupled with superior safety and combinability compared to other VEGF/VEGFR inhibitors.VEGF/VEGFR inhibitors.

ACTB1003: First-in-class oral kinase inhibitor with multiple modes of action

ACTB1003 is a unique, oral, Phase 1 kinase inhibitor that targets cancer cells through multiple modes of action. ACTB1003 inhibits cancer cell growth by targeting all four FGF receptors, which are mutated in a number of human cancer types. ACTB1003 also directly induces apoptosis by targeting the RSK and S6K kinases in the PI3K pathway, all at low nanomolar concentrations. No other anti-cancer agent on the market or in development inhibits the same combination of targets. In addition, since ACTB1003’s targets are often mutated in human cancers, there is the potential to select indications and patients based on the genetic profile of their disease. An IND for ACTB1003 was accepted by the US Food and Drug Administration (FDA) in 2010. Phase 1 clinical trials in multiple cancer indications are planned.

ACTB1010: Aurora Kinase inhibitor

ACTB1010 is a potent and selective oral inhibitor of the mitotic kinases Aurora A and Aurora B, known to be overexpressed in many human cancers. ACTB1010 was rationally designed to overcome the drawbacks of first generation Aurora kinase inhibitors in the areas of potency, selectivity, administration, and safety. ACTB1010 has shown excellent safety in pre-clinical experiments and has achieved tumor regressions in both solid and hematological tumor models. Advanced pre-clinical work is ongoing in preparation for an IND filing.

ACTB1011: Mutant ABL inhibitor

ACT Biotech’s late preclinical candidate ACTB1011 is a potential best-in-class oral inhibitor of mutant BCR/ABL tyrosine kinase, including the difficult to address T315I mutant. ACTB1011 will initially be targeted for leukemia patients who are resistant to imatinib, desatinib and or nilotinib based on outgrowth of leukemic cells with mutant ABL tyrosine kinase. More than thirty-eight such mutations have been identified in the kinase domains of ABL, leading to a high unmet need for those patients who carry these mutations, particularly those who carry the mutation known as T315I. ACTB1011 delivers a superior survival benefit in mouse xenograft models expressing common mutations including T315I. ACT Biotech is initiating IND enabling studies with ACTB1011.

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