Products

SP1049C is a proprietary intravenous composition of BioMod™ polymers and doxorubicin as API. It is a clinical phase 3-stage novel anticancer chemotherapeutic drug candidate for the treatment of cancers that are resistant to doxorubicin. SP1049C is particularly active in multi-drug resistant (MDR) and metastatic cancers. Ability to effectively treat these cancers represents an important step in dealing with an unmet medical need.

A phase 1 study showed SP1049C to have an acceptable safety profile and a phase 2 proof- of-concept study has demonstrated improved therapeutic efficacy in patients with otherwise chemotherapy refractory, poor prognosis cancers. It is the first in class and unique among anthracycline chemotherapeutic products.

In the US, SP1049C is designated as an orphan drug in carcinoma of the esophagus and in gastric cancers. It is ready to enter a pivotal international clinical phase 3 study. The design of this trial has been reviewed and agreed to with the FDA under a Special Protocol Assessment (SPA) procedure.

If successful SP1049C will be the first drug approved for the treatment of relapsed patients with metastatic adenocarcinoma of the esophagus, and some other upper gastrointestinal tract Cancers. Subsequent phase 2 trials are planned to expand labels for the treatment of chemotherapy refractory colon, refractory breast, non-small cell lung cancers (NSCLC) and leukemias.

Mechanism of action

SP1049C enables increased accumulation of doxorubicin in MDR tumors. Specific signalling by the polymeric components disrupts mitochondrial function in resistant tumor cells that results in an apoptotic signal that is synergistic with doxorubicin action. Recent independent research has demonstrated SP1049C to be highly selective in reducing cancer stem cell development.

Preclinical studies have shown that:

• SP1049C accumulates in tumor tissue more effectively than doxorubicin.
• Its distribution in normal tissues is similar to doxorubicin.
• SP1049C is active against doxorubicin resistant and as well as doxorubicin sensitive cancers cells.
• SP1049C safety profile is comparable to that of doxorubicin.

Clinical phase 2 studies have shown that:

• SP1049C has high activity as a single agent with response rate of 47% (by WHO criteria) and 41% (by RESIST) in non-resectable stage IVb patients with adenocarcinoma of the esophagus.
• Clinical benefit (response rate plus stable disease) was recorded in 89% of patients.
• Median survival was 10 months, which is comparable to the most efficient three-drug combinations used today.

SP1031C is a proprietary bendamustine composition utilizing BioTrans™ nanotechnology that shelters bendamustine reactive groups by a colloid nanomatrix, increasing its half-life in plasma. As a result SP1031C has increased stability of the drug active-form in plasma and improved biodistribution in tissues.

The drug is presently marketed in the US as Treanda® to treat chronic lymphocytic leukemia (CLL) and non-Hodgkin’s lymphoma (NHL). Insufficient chemical and metabolic stability of the drug limits its use to hematological cancers and prevents its application in solid tumors.

Preclinical data show SP1031C to have improved pharmacokinetics, efficacy and tolerabilitycompared to Treanda:

• Efficacy of SP1031C was evaluated in breast and lung carcinoma mouse models, showed SP1031C to be significantly more active than Treanda.
• Cytotoxicity of the composition has been tested in a panel of cancer cell lines that showed SP1031C to have a significantly higher activity than bendamustine.
• In terms of plasma pharmacokinetics and tissue distribution studies, SP1031C is superior to Treanda.
• SP1031C is significantly less toxic than bendamustine.

SP1063C is a novel composition of SN-38, a potent topoisomerase I inhibitor. Presently the therapeutic use of SN-38 is made possible with a prodrug called irinotecan. Irinotecan requires metabolic conversion in the patient’s body in order to release SN-38. Such conversion is very inefficient in humans and gives rise to problems of high toxicity and inter-patient variability.

SP1063C solves both problems by solubilizing SN-38 using Supratek’s proprietary BioTrans™ platform. As a result, the SP1063C composition makes SN-38 directly bioavailable and avoids the problems associated with irinotecan, the pro-drug. The direct delivery of SN-38 increases the therapeutic index of SP1063C and opens possibilities for its use in additional indications, including gastric cancer, metastatic breast cancer and SCLC. Lowered toxicity may also permit SP1063C to be used as a systemic cancer maintenance drug.

Direct administration of SN-38 by i.v. infusion requiring no metabolic conversion may potentially provide a number of clinical benefits:

• Reduced toxicity (diarrhea and other GI toxicities)
• Reduced in inter-patient variability

Preclinical data where SP1063C was compared to irinotecan show that:

• SP1063C has a significantly better pharmacokinetics compared to irinotecan.
• SP1063C was found to be significantly less toxic than irinotecan.
• SP1063C was highly active in solid tumors including breast, colon, and lung carcinoma mouse models. Studies in dogs have demonstrated that a therapeutically efficient and safe dose of SP1063C is over two orders of magnitude lower compared to that of irinotecan.

Cabazitaxel (trade name Jevtana) is a semi-synthetic derivative of a natural taxoid. It was developed by Sanofi-Aventis and was approved by the U.S. FDA for the treatment of hormone-refractory prostate cancer in 2010. It is a microtubule inhibitor. Common adverse events of cabazitaxel treatment include neutropenia (and febrile neutropenia) and diarrhea. The combination of cabazitaxel and prednisone is an important new treatment option for men with docetaxel-refractory metastatic prostate cancer, but this agent requires careful administration with appropriate monitoring (especially in men at high risk of neutropenic complications).

Although cabazitaxel has greater efficacy than docetaxel, nevertheless, there is still substantial resistance, as evidenced in numerous preclinical studies. Supratek undertook to improvedcabazitaxel to further boost its efficacy against chemoresistant cancers.

SP1015C is an injectable BioMod™ nanomedicine that employs nontoxic polymeric nanoparticles to solubilise cabazitaxel in aqueous medium. The nanoparticles combine the drug with an amphiphilic compound that selectively disrupts the functionality of mitochondria in chemoresistant cancer cells, thus synergistically enhancing anticancer activity of the cabazitaxel. The increased activity of SP1015C is attributed to its ability to inhibit ATP production by uncoupling mitochondrial respiration chain and by allowing an unimpeded access of the cytotoxic into MDR cancer cells to kill them. Preclinical data show SP1015C to possess improved activity against drug resistant malignancies.

SP1012C is a BioMod™ injectable nanomedicine that employs nontoxic polymeric nanoparticles designed to solubilise the cytotoxic agent docetaxel in aqueous medium. Additionally, the nanoparticles combine the drug with an anti-MDR component, an amphiphilic compound that synergistically enhances anticancer activity of the drug in the resistant cells. The increased activity of SP1012C appears to be due to its ability to inhibit ATP production by uncoupling mitochondrial respiration chain and consequently inhibiting active efflux mechanisms, which allows an unimpeded access of the cytotoxic into multidrug resistant cancer cells and kill them.

The novel composition was shown to have higher potency against drug resistant cell lines as compared to docetaxel. The ongoing animal studies demonstrated that SP1012C had significantly higher efficacy than Taxotere.

SP1060C-O is a proprietary, BioMod™ based, orally bioavailable composition of topotecan that increases the bioavailability of the active lactone form of the drug.

Preclinical studies have shown SP1060C-O to be significantly more active compared to topotecan administered either by intravenous injection or taken orally. Relative to other known formulations of campthotecins, SP1060C-O provides the highest lactone-to-carboxylate ratio in plasma, which appears to result in a significantly higher anticancer activity.

SP1060C-O selectively inhibits a set of ATP dependent transporters that are responsible for intestinal absorption of the lactone form of topotecan without affecting the activity of transporters that are involved with the carboxylate form of the drug. The BioMod™ carriers used in this product candidate have a low oral bioavailability and are unlikely to produce any significant drug interactions.

Preclinical studies have shown that:

• SP1060C-O provides a selective and increased intestinal absorption of topotecan lactone.
• Oral administration of SP1060C-O significantly increased tumor/plasma ratio of the drug levels and a reduced drug accumulation in filtering organs.
• SP1060C-O was highly active in several animal models