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Folates as possible cancer treatment - Endocyte a rising star in cancer treatment
Endocyte, a biopharmaceutical company specializing in predicative medicine and targeted drugs is designing small molecule drug conjugates intended for cancer treatment. In addition to its small molecule drug conjugates the company markets companion drugs intended as screening agents, the “companion drug imaging agent”, for the purpose of finding out what patients will be affected and to which degree by their therapies. This highly individualized approach is intended for the treatment of platinum-resistant ovarian cancer, but other targeted cancer and disease drugs are already in the pipeline research of this company.

Endocyte was formed in 1996 with a goal of designing a targeted drug delivery system discovered by Philip Low, Ph.D., at nearby Purdue University. Dr. Low, now lead researcher at Endocyte, discovered that folate can be used as a transport and delivery system for drugs, considering that most cells poses folate receptors. Folate, a B vitamin, is one of the key ingredients needed for cellular division. All cells exhibit it, but cancer cells exhibit it in a far greater quantity, considering that their division mechanism is out of control and that cancer cells multiply very rapidly. Moreover, cancer cells in particular overexpress the folate receptor and use a different pathway than healthy cells to obtain it. This specific mechanism and need for folate of cancer cells is exactly what Endocyte researchers have exploited to create a unique targeted drug conjugate which will allow selective killing of cancer cells, with minimum or no toxicity to surrounding tissues.

“This means that we can target highly potent drugs directly into cancer cells without harm to healthy cells,” says Ron Ellis, president and CEO of Endocyte.

Many potent cancer drugs have been developed and tested, and the vast majority of them have since been abandoned due to severe side effects and surrounding tissue toxicity. Endocyte used a different approach, they used an older, abandoned drug and attached it to folate, in an attempt to target cancer cells specifically and avoid damage to the surrounding tissue. The newly created drug, called vintafolide (MK-8109/EC145) is currently in phase III clinical trials for platinum resistant ovarian cancer and has so far shown to be very effective.

Vintafolide has a companion drug, etarfolatide (EC20) used to screen patients most likely to respond to treatment by vintafolide. An authorization of vintafolide and etarfolatide, for conditional approval, was obtained from the European Medicines Agency earlier this year.

The chemotherapeutic component of vintafolide is a type of vinca alkaloid absorbed exclusively by cancer cells. For the treatment of patients with platinum-resistant ovarian cancer, vintafolide is combined with pegylated liposomal doxorubicin, under the brand name Doxil. The company says that pairing up this drugs increases the chance of killing cancer cells, since using multiple drugs in combination has show effective in overcoming the cancer cells acquired immunity to therapeuticals.

“Vintafolide’s toxicity profile gives us great flexibility to combine it with other drugs,” says Ellis.
Using drugs combines in this way has been very dangerous to attempt until now, because of their cumulative toxicity.

Vintafolide has been tested in an international, multicenter Phase II trial consisting of 149 women with platinum-resistant ovarian cancer. Patients received vintafolide plus Doxil or just Doxil until either disease progression or death. The primary goal was progression-free survival. Patients taking vintafolide plus Doxil had a median progression free survival of 5 months, compared to 2.7 months for patients receiving Doxil alone.
However, in patients who tested the most positive for a specific folate receptor, the delayed progression-free survival increased from 1.5 months to 5.5, or 260%. “If you don’t have the receptor, the drug doesn’t work as well. That’s a remarkable result,” says Ellis. A Phase III trial of vintafolide in platinum-resistant ovarian cancer is under way, as well as a Phase II/III trial of vintafolide in non-small-cell lung cancer.

This approach was dubbed the “warhead” approach. Treatment for other types of cancer will consist of attaching different drugs to folate, using the specific folate metabolism of cancer cells. Other old, abandoned drugs have begun a revival with this new approach, including drugs such as platinums, microtubule destablizers, and vinca alkaloids.

“We’re designing versions that are a thousand to a million times more potent, yet less toxic,” says Ellis.

Endocyte is a rising star in the drug market, with promising stocks and even more promising research.
Location: 3000 Kent Avenue, Suite A1-100, West Lafayette, IN 47906
Phone: (765) 463-7175
Ron Ellis, President and CEO
Philip Low, Ph.D., CSO
Number of Employees: 75
Focus: Endocyte develops targeted small molecule drug conjugates and companion imaging diagnostics to treat cancer and other diseases.
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