Alocrest™ is a new, targeted, nanoparticle-encapsulated, cancer therapeutic specifically designed to improve patient outcomes by combining the potential for enhanced efficacy with an absence of increased toxicity compared with conventional vinorelbine. Alocrest consists of vinorelbine, a potent vinca alkaloid anti-mitotic, encapsulated in the aqueous core of proprietary sphingomyelin-based liposomes called Optisome™. This distinct formulation has been developed to facilitate high-concentration, targeted drug delivery and sustained drug release kinetics. In animal models, this unique technology resulted in prolonged plasma circulation (100-fold increased area under the concentration time curve) and 9.5-fold enhanced cancer tissue drug penetration and accumulation compared to that achievable with un-encapsulated, standard vinorelbine. The intra-tumoral vinorelbine dose intensification facilitated by the Optisome technology is expected to improve cancer cell killing beyond the capability of standard vinorelbine. The prospect of providing enhanced anti-cancer activity without enhanced toxicity is of particular importance in the treatment of elderly cancer patients and those with marginal performance status (PS). The novel technical characteristics and use of Alocrest are protected by a series of US and ex-US patents.

Alocrest™ is being developed to improve the standard of care in adults with newly diagnosed or relapsed solid tumors such as non-small cell lung cancer (NSCLC) and breast cancer. A Phase 1 dose-escalation trial of Alocrest administered every 21 days demonstrated promising anti-cancer activity (47% disease control rate) across a range of doses, as well as acceptable and predictable toxicity in heavily pre-treated persons with advanced solid tumors. In contrast to historical reports for vinorelbine, there were no cases of peripheral vein irritation associated with intravenous Alocrest. Pre-Phase 2 planning is focused on evaluating Alocrest administered every 21 days against standard vinorelbine given weekly in elderly and PS 2 NSCLC patients.

Close

Brakiva™ is a new, targeted, nanoparticle-encapsulated, cancer therapeutic specifically designed to improve patient outcomes by combining the potential for enhanced efficacy with an absence of increased toxicity. Brakiva consists of topotecan HCl, a potent semi-synthetic derivative of camptothecin, encapsulated in the aqueous and acidic core of proprietary sphingomyelin-based liposomes called Optisome™. This distinct formulation has been developed to facilitate high-concentration, targeted drug delivery and sustained drug release kinetics. The acidic Optisome core is critical to the maintenance and delivery of the non-hydrolyzed and fully active form of topotecan to the target cancer tissue. In animal models, this unique technology resulted in prolonged plasma circulation and 10-fold enhanced cancer tissue drug penetration and accumulation compared to that achievable with un-encapsulated, standard topotecan. A 10- to 20-fold increased milligram for milligram anti-tumor activity of Brakiva compared to standard topotecan was demonstrated in non-clinical models. The intra-tumoral topotecan dose intensification facilitated by the Optisome technology is expected to improve cancer cell killing beyond the capability of standard topotecan. The prospect of providing enhanced anti-cancer activity without enhanced toxicity is of particular importance in the treatment of patients with relapsed and refractory solid tumors such as small cell lung cancer and ovarian cancer. The novel technical characteristics and use of Brakiva are protected by a series of US and ex-US patents.

Brakiva™ is being developed to replace standard topotecan therapies in persons with newly diagnosed or relapsed solid tumors such as small cell lung cancer (SCLC) and ovarian cancer. A two-arm, Phase 1, dose-escalation trial of Brakiva administered every 21 days or on days 1 and 8 of a 21-day cycle is ongoing in mostly heavily pre-treated adults with advanced solid tumors. Based on preliminary encouraging tolerability and activity, pre-Phase 2 planning is focused on evaluating Brakiva administered every 21 days in women with relapsed ovarian cancer.

Close

Marqibo® is a new, targeted, nanoparticle-encapsulated, cancer therapeutic specifically designed to improve patient outcomes by combining the potential for enhanced efficacy with the potential for reduced toxicity. Marqibo consists of vincristine sulfate, a potent vinca alkaloid anti-mitotic, encapsulated in the aqueous core of proprietary, sphingomyelin-based liposomes called Optisomes™. This distinct formulation has been developed to facilitate high-concentration, targeted drug delivery and predictable, first-order, continuous drug release kinetics. In animal models, this unique technology resulted in enhanced cancer tissue drug penetration and accumulation compared to that achievable with un-encapsulated, standard vincristine. In human clinical trials, Marqibo facilitated marked vincristine dose-intensification compared to historical standard vincristine dosing. The dose-intensification results from both a larger milligram dose per unit of body surface area (2.25 mg/m² versus 1.4 mg/m²) and elimination of the need for the dose capping that is routinely applied to standard vincristine. The net results from Marqibo are individual (2-3-fold increase) and cumulative (up to 10-fold increase) vincristine dose increases that may facilitate activity against relapsed and refractory cancer. Liposomal drug delivery may limit toxicity despite dose-intensification. The novel technical characteristics of Marqibo are protected by a series of US and ex-US patents.

Marqibo® is being developed to provide a standard of care in adults with Philadelphia chromosome (Ph) negative acute lymphoblastic leukemia (ALL) in second or greater relapse or that has progressed following two or more prior lines of anti-leukemia therapy. Marqibo also has the potential to improve the standard of care in adults and children with newly diagnosed hematologic cancers including ALL and non-Hodgkin's lymphoma (NHL). Encouraging single-agent anti-cancer activity has been demonstrated in persons with relapsed aggressive NHL and in relapsed, advanced, and at times refractory adult Ph-negative ALL. Marqibo side effects were predictable and manageable in these study populations and there were no new unexpected toxicities observed. The recently reported Phase 2 RALLY study in adult Ph-negative ALL is intended to support US accelerated approval. Phase 3 programs will study Marqibo as part of front-line, multi-agent therapy in older adults with ALL, older adults with aggressive NHL, and children with ALL are in advanced planning.

Close

Menadione Topical Lotion (MTL) is a first-in-class, topical formulation of menadione (vitamin K3) being developed for the prevention and treatment of the common, painful, unsightly, and cancer treatment-limiting skin toxicity (“rash”) reported to be caused by both small molecule (e.g., Tarceva®) and antibody (e.g., Erbitux® and Vectibix®) epidermal growth factor receptor (EGFR) inhibitors. The menadione in MTL has phosphatase inhibitory activity, distinct from other vitamin K species, that can normalize and up-regulate EGFR cellular signaling. Following topical application, the menadione in Talon’s proprietary MTL formulation affects skin EGFR at the dermal-epidermal interface without any appreciable systemic absorption. MTL targets the underlying cause of the rash with negligible potential for interference with EGFR inhibitor therapy at the tumor level. Talon has issued or pending patents (U.S. and E.U.) covering mechanism, use, and formulation.

EGFR inhibitors are prescribed for the treatment of lung, colon, breast, pancreas, and head & neck cancers. Up to 90% of EGFR inhibitor exposed patients develop early onset skin rash involving the face, neck, and upper torso, with up to 30% of affected patients stopping EGFR inhibitor therapy because of rash alone. The rash may indirectly and adversely affects cancer outcomes by leading to sub-optimal drug dosing and a lack of compliance. Empiric combination oral antibiotic and over the counter topical agent regimens have not been shown to address the rash etiology and are believed to be generally ineffective. There are no approved products that address this growing cancer treatment-related toxicity.

Talon is developing MTL for patients treated with an EGFR inhibitor in order to prevent and treat rash, allow EGFR inhibitor dose optimization, and improve cancer patient outcomes. The recently completed Phase 1 program consisted of two trials and demonstrated that MTL is generally safe and well tolerated. The Phase 1 program identified the apparent maximum tolerated lotion strength and provided preliminary evidence of lotion ability to mitigate rash severity. Phase 2 planning is underway.

Close