BIOTECHCLINICIAN Weekly

I hope everyone had a great weekend. Beautiful fall weather here, it has been great running weather, I hope it lasts for a while. To the industry news of the week. Cell Pathways announced a collaboration with Rhone-Poulenc Rorer (NYSE:RP) to conduct clinical trials investigating the therapeutic potential of Aptosyn (exisulind) in combination with Taxotere (docetaxel). The two companies will jointly share the cost of this effort. The initial clinical trial will investigate the combination of Aptosyn, Taxotere and carboplatin chemotherapy in previously untreated non-small cell lung cancer. Other trials will investigate Aptosyn and Taxotere combinations in breast, prostate and pancreatic cancers. The initial trial is a Phase I study to evaluate escalating doses of Aptosyn in combination with a standard regimen of Taxotere and carboplatin to determine safety and dosing. The trial will be immediately followed by a Phase II open-label efficacy study of the three-drug combination regimen, designed to support future studies and potential product registration. Earlier studies had shown synergistic activity between Aptosyn, taxane and platinum compounds in animal and cell culture models of lung cancer. This agreement does a number of things for CLPA. It allows the company to expand the trial base and future uses of Aptosyn. In addition to that, they have found a way to get another company to help fund the studies. All this without giving up any rights to the drug (as opposed to other early stage companies who end up essentially giving away their drug for a revenue share). CLPA continues undervalued (if the drug works) and will until we have further news about efficacy.

ImClone Systems Inc. had an interesting week. In documents filed relating to a planned public offering, IMCL became aware of a U.S. patent Genentech Inc. (NYSE:DNA) holds on an anti-cancer technology similar to the technology used in ImClone's lead experimental cancer drug. ImClone stated attorneys had reviewed Genentech's patent and determined ImClone could commercialize the drug (C225) without infringing the Genentech patent. ImClone Chief Executive Samuel Waksal stated that Genentech had never contacted ImClone about the patent situation, and that Genentech has not threatened any patent-infringement action against ImClone. We will probably look back at this as a buying opportunity (with the stock touching $16 after the announcement). IMCL also announced the initiation of patient treatment in a multi-center Phase II clinical trial evaluating C225, in combination with the chemotherapeutic agent CPT-11 in 98 patients with refractory colorectal carcinoma. This company is a good example of the volatility that occurs in biotech investing ($39 to $16 back to the mid $20s). If you can ignore the short-term changes in price and stay focused on the long term, there are always opportunities.

BioChem Pharma launched Heptodin (lamivudine) in China (which has the highest prevalence of the disease in the world). Heptodin has been granted a Class 1 drug certificate in China, offering the advantage of manufacturing exclusivity for the product in the treatment of hepatitis B for a period of eight years. Hepatitis B is one of the most common infectious diseases in the world with 350 million people infected. Lamivudine is already available in a number of countries including South Korea, the US, Canada, the UK, Germany and France. The revenue generated from this drug should continue to expand rapidly for the foreseeable future. This gives the company a significant revenue stream to fund R&D in the future.

Sepracor entered into an agreement with Rhone-Poulenc Rorer, a unit of Rhone-Poulenc SA (NYSE: RP), that gives Sepracor exclusive license to preclinical, clinical and post-marketing surveillance data package relating to zopiclone, its isomers and metabolites, to develop, make, use and sell (+)-zopiclone in the United States. Pursuant to the agreement, RPR retains the right to manufacture (+)-zopiclone in the U.S. for non-U.S. markets. Zopiclone is a non-benzodiazepine rapid-acting hypnotic for the treatment of sleep disorders. In preclinical and clinical studies, Sepracor has shown that the isomer, (+)-zopiclone, is predominately responsible for the hypnotic effect and has the potential to reduce certain side effects. The U.S. market for prescription sleep products is currently over $600 million and growing at a rate of 20% per year. Sepracor filed its investigational new drug application (IND) on (+)zopiclone in the second quarter of 1999 and is currently completing Phase I studies. The Company plans to initiate large Phase II/III pivotal studies in the first half of 2000. This just adds another drug into their continually expanding pipeline. SEPR remains poised to be a large, well diversified pharmaceutical company early in the next century.

Isis Pharmaceuticals and Rhone-Poulenc Rorer announced they have signed a three year collaboration to assess genes identified within RPR's genomics programs using Isis' Antisense Target Validation technology. This collaboration will give Isis with valuable information on these targets to assist in the development of novel antisense drugs. This is Isis' second target validation collaboration. RPR will provide Isis with sequence information on a number of novel gene targets. RPR has an option to expand the number of gene targets. Using its proprietary Rapid Throughput Screening (RTS) technology, Isis will design optimized antisense inhibitors for these targets. RPR will then use these antisense inhibitors to identify the function of the gene, its role in molecular pathways associated with the disease, and prioritize the gene targets for development. Isis will develop antisense inhibitors for the targets provided by RPR. RPR will pay Isis research fees and milestone payments based on the success of the program.

Trimeris, Inc. (NASDAQ: TRMS) and Roche announced 16-week results from a Phase II clinical trial (T20-205) evaluating the safety and antiviral activity of T-20, a member of a new class of anti-HIV compounds known as fusion inhibitors. Results at 16 weeks showed that 33 of 55 (60%) heavily pre-treated patients who were given T-20 in combination with oral antiretroviral agents responded with a clinically significant reduction of HIV in the blood. Of these, 20 of the 55 (36%) had virus levels below the level of quantification. No patients discontinued the trial due to T-20-related adverse events or intolerance of the twice-daily subcutaneous injection. This is important to the company. There has been some concern about daily injections being a problem with drug delivery.

SuperGen Inc. (NASDAQ: SUPG) acquired the worldwide rights to decitabine, a chemotherapeutic agent owned by Pharmachemie, a subsidiary of Israel-based Teva Pharmaceuticals. The acquisition involved an exchange of SuperGen shares. Decitabine has received orphan drug status from the FDA. It is currently in clinical testing for acute leukemias and other hematological malignancies at Memorial Sloan-Kettering Hospital in New York City, M.D. Anderson Cancer Center in Houston, and Johns Hopkins Medical Center in Baltimore. Decitabine has been used in over 1,000 patients, and pursuant to discussions with the Food and Drug Administration, it has been agreed that there will be an accelerated development strategy for the compound.

Proneuron Biotechnologies, Inc. has received approval from the FDA for a Phase I clinical trial of the company's spinal cord cell therapy for newly-injured paraplegic patients. Proneuron's spinal cord cell therapy has shown encouraging results in animal studies. The procedure consists of taking white blood cells (macrophages) from the injured patient's own blood and processing them in a laboratory. The activated cells are then administered to the patient's spinal cord. Macrophages promote wound healing in most body tissues, but are normally unable to enter the spinal cord in large numbers. Proneuron's spinal cord cell therapy must be started within a few days of the injury. This would be magnificent news to anyone injured in the future.