BioIsrael

TPI: Puts The Best Face on Acne

Tamarkin Pharmaceutical Innovation (TPI), a young pharmaceutical company, has done a remarkable job in going from establishment to successful Phase II clinical results for its lead compound, a topical treatment for acne and related skin disorders, in only three years.

The company was founded in 1998 by Dr. Dov Tamarkin and Dr. Arie Giniger, both with long experience in skin treatment. Dr. Tamarkin, who is the inventor of the technology, brings along a resume that includes R&D management at biomedical startups as well as management of Teva’s drug development programs in the fields of dermatology and infectious diseases and R&D management at Portman Pharmaceuticals.

“I reproduced my experiences as R&D manager at Elad Ventures, and in senior R&D management positions at Portman Pharmaceuticals and Teva, in order to build TPI in both cost and time effective manners. TPI attained development milestones quickly and on a small budget, reaching the current phase of development on less than $2 million, Tamarkin said.

The company has completed initial phase II clinical trials at Belgian hospitals for TU-2100, a proprietary compound that is actually a combination of two lesser known acne treatments, salicylic acid and azelaic acid. Individually, these compounds have minimal efficacy in fighting acne, which is estimated to effect about 95 percent of American young adults and represents a $1 billion treatment market. However, TPI’s synthesis of the two compounds into what the company terms a “Dual Action Pro-drug” has resulted in a treatment that has demonstrated superior efficacy to Retin A, the current gold standard. In an initial 42-person study, it has been shown to act faster and diminish more acne lesions than retin A, while causing no irritation or other side effects.

According to Tamarkin, the efficacy of TU-2100 lies in its ability to attack all the causes of acne, through a series of mechanisms that are not yet fully understood. At the root of acne is a process by which testosterone is converted to DHT, a hormone which causes sebum overproduction, especially at adolescence. A cascade of effects result, which include the creation of keratin plugs that block pores and prevent the release of sebum. This in turn promotes the proliferation of bacteria within the system, and the inflammation that results in visible acne. Current acne treatments, which include benzoyl peroxide for cases of mild to medium severity, and systemic treatments such as Roche’s Roaccutane, are only somewhat effective, and cause side effects including dry skin and increased photosensitivity. Potential side effects for Roaccutane are so severe that the FDA requires patients to sign their consent before taking the medication.

Tamarkin believes that TU-2100’s efficacy and safety are assisted by the fact that the molecule dissolves only in oil, and therefore penetrates very effectively into the sebaceous glands of the skin, where it is the first topical treatment to have shown the ability to inhibit excess sebum production, while not penetrating as deeply as the blood stream itself.

“In 1997, prior to founding the company, I had the compound tested by Dr. Albert Kligman at the University of Pennsylvania, who invented the use of retin A as an acne treatment,” Tamarkin said. “The study showed that sebum production was inhibited by 30 to 40 percent. The result was not to dry the skin, but to normalize, and normalization is ultimately what one looks for.”

“Additionally, because the molecule is extremely hydrophobic, it does not penetrate to the lower layers of skin and into the circulatory system. TU-2100 could not be detected in the blood of individuals involved in the Phase II trials, which is a great relief from the point of view of FDA approval,” Tamarkin said.

TPI recently entered a licensing agreement with Istituto Biochimico Italiano Giovanni Lorenzini (IBI), an Italian pharmaceutical company, for the mutual development of TU-2100 as a topical anti-acne medication. Under terms of the agreement, IBI will conduct a multi-center Phase IIb clinical study in several centers in Europe, the purpose of which will be to collect further safety and dosage information in advance of Phase III trials which the company hope to initiate by the end of 2002.

“We see the total development cost of TU-2100 to be in the range of $12 to $20 million, however our working assumption is that most of this cost will be covered by partners, of which IBI is the first,” Tamarkin said. “Our strategy is to have one good partner in the US, and partners in Europe sufficient to cover the continent. Our partners will be able to promote development of the product and bring it to market in the most effective way.”

Tamarkin expects to market TU-2100 initially as a prescription medication for acne, shifting to an over-the-counter (OTC) formulation in three to five years. “It isn’t likely that the FDA will approve of TU-2100 as an OTC treatment initially, since it will want to collect additional post-marketing safety data first, and this is only possible while TU-2100 is a prescription medication,” he said.

Tamarkin stressed that the company is developing a platform of compounds for the treatment of skin disorders, as well as additional indications including baldness and psoriasis. The connection to baldness comes from TU-2100’s conceivable ability to inhibit the conversion of testosterone into DHT, the hormone known to cause excess sebum secretion, but which is also curiously responsible for the growth of hair on all parts of the body except for the head, where it actually inhibits hair growth for reasons yet to be understood. “Our objective is to develop additional molecules on the same platform, as well as new platforms, which we’ll take into the proof of concept and initial clinical trials stages,” Tamarkin said.

Investment in the company to date has been from private Israeli investors, as well as founders Tamarkin and Giniger. The company is currently seeking a new round of funding, and has entered negotiations with foreign institutional investors to provide the amount of capital needed to fund the company going forward. Tamarkin said that the company has applied for patents in all relevant markets. A broad patent covering the company’s compounds and all potential uses in humans was issued in the US in January of this year.

Further details about the Tamarkincan be viewed at their Pharmalicensing profile here.

and you can visit their licensing opportunity profile for TU-2100 - Anti Acne Topical Medication here.

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