The biggest news at this year’s ASCO came from BMS’ (BMY) PD-1 antibody, BMS-936558. This antibody belongs to a new class of antibodies that stimulate patients’ immune system to attack cancer. This approach has been recently validated with another BMS antibody, Yervoy, which was approved last year for melanoma.
Based on results presented at the meeting, BMS-936558 is superior to Yervoy by any measure. In fact, it is probably one of the most promising oncology drugs ever to be tested in humans. It induces tumor shrinkage in a substantial portion of patients, creates an immune response that keeps the disease under control for long periods and it does so with limited side effects. To make things even better, there might be a way to pre-select patients who are more likely to respond to this agent. Continue reading →
Immunogen (IMGN) concluded the week with a market cap of ~$1B, up 200% in less than a year. This valuation is quite unusual for a company that ascribes the vast majority of its value from a 3-5% royalty stake in a single drug – Roche’s T-DM1. T-DM1, which utilizes Immunogen’s antibody-drug conjugate (ADC) technology, comprises of Herceptin conjugated to a drug payload. It is in two phase III trials and multiple phase II studies in breast cancer. If proven effective, many believe T-DM1 will eventually replace Herceptin, at least in certain treatment lines.
After a challenging year, Exelixis (EXEL) is finishing 2010 on a positive note, with the help of promising data for its lead agent, XL184. Last week at the EORTC conference, the company published data from a large phase II study in multiple cancer types. The results came at a crucial time for Exelixis, as many were questioning the value of XL184 following BMS’ (BMY) decision to opt-out of its development. As discussed in a previous post, when a partner like BMS dumps a late stage clinical asset after a licensing payment of over $150M, the alarm bells start ringing.
XL184 inhibits several targets, primarily VEGFR2 and Met. As a multi-targeted kinase inhibitor, the drug has some overlap with other drugs, primarily VEGFR inhibitors. There are two drugs that inhibit VEGFR (in addition to other targets) currently in the market as well as a long list of VEGFR inhibitors in late stage clinical testing from GSK (GSK), AstraZeneca (AZN), BMS and Aveo (AVEO). The main question regarding XL184 is whether the drug has a differentiated clinical profile in comparison to other VEGFR inhibitors. Based on recent data presented at EORTC the answer is a resounding “YES”. Continue reading →
Array’s (ARRY) shares keep on fluctuating in the $2.5-$3.5 range, relatively unchanged from the beginning of 2010. It seems that the market is having trouble assessing the real value of the company and its pipeline, which includes 13 (!) drugs in clinical trials. With a market cap of ~$170M, the market puts an average price tag of $13M per asset, a ridiculously low valuation (assuming no value is assigned to the company’s discovery platform). The company’s long term debt (due in 2014) could be partially blamed for this anomaly, but the problem seems to be more related to the company’s business model. The good news is that during the next year the company is looking at multiple events that might change the way Wall Street views Array. Continue reading →
On top its JAK programs, Incyte has been developing two additional programs it intends to out-license. The first program is INCB13739 for diabetes, which already reached clinical proof of concept and could be licensed imminently. The second program, INCB7839 for breast cancer, is less advanced but could become very interesting later this year depending on data from an ongoing trial.
Earlier this month, Micromet (MITI) concluded an impressive public offering of $75M, approximately 20% of the company’s market cap. The offering illustrates the transformation the company has undergone from an anonymous biotech play into a recognized industry leader. This is also echoed by the growing attention from Wall St. When I first wrote about Micromet in 2007, the company was covered by a single analyst, RBC’s Jason Kantor, who was one of the first to see the potential in Micromet’s platform. Today the stock is covered by six additional research analysts.
A drug with an almost certain approval and immediate sales potential of hundreds of millions of dollars is an asset very few biotech companies possess. In that sense, Incyte (INCY), which is developing a breakthrough drug for blood disorders, represents a unique opportunity in an industry plagued by risk and uncertainty. Incyte is also unique in its problematic capital structure, which makes an otherwise simple investment decision into a tricky one.
The past 12 months have been anything but boring for Micromet’s shareholders (MITI). Last summer, Micromet’s stock climbed to $7 following excellent clinical data (discussed here) and a landmark publication in Science Magazine (discussed here), but since then the company has lost half of its value. Volatile trading is quite standard for small, cash burning biotechnology companies, however, Micromet’s case was particularly frustrating.
Micromet invented a new class of antibodies it calls BiTE (Bispecific T-Cell Engager) antibodies. Unlike conventional antibodies, BiTE antibodies bind two targets, the first target is presented on a cancer cell and the second is presented on an immune cell. The simultaneous binding of both cells by the BiTE antibody can redirect the immune cell to attack the cancer cell, thus exploiting the body’s natural immune mechanisms to fight cancer. Conceptually, a BiTE antibody is similar to cancer vaccines, which also aim at producing an immune response against tumors. Despite a history of failures in the field of immunostimulating antibodies, it looks like Micromet has found the right formula.
There is always a debate regarding market efficiency and to what extent stock prices represent the available information about a company. Micromet’s (MITI) surge last week shows that in some cases, the market is far from being efficient. The spike of more than 35% in the last two trading sessions is attributed to the publication of a short article in Science Magazine, one of the world’s most prestigious scientific journals. The article contained clinical data from an ongoing phase I trial of Micromet’s lead candidate, MT103 (partnered with Medimmune). The data was spectacular, showing a strong, dose dependent response in concert with a good safety profile, exactly the kind of data that can put a small biotech in the spotlight. Ironically, the article contained data which has already been presented more than two months ago at the ICML in Switzerland.
Regardless of whether market reaction was justified, publishing clinical data at such an early stage in Science should be viewed as an indication for the scientific community’s embrace of Micromet and its BiTE platform. The BiTE platform relies on monoclonal antibodies for stimulating the patient’s immune system to attack cancer cells that have managed to evade or suppress the body’s immune response. Although most attention is given to the first product from the platform, MT103, it can generate an unlimited number of agents against a variety of cancers, making it a potential revolution in the way cancer is treated.
Forty years after the accidental discovery of their anti-cancer properties, platinum based compounds represent one of the most important classes of oncology drugs. Platinum compounds are effective in treating a wide array of malignancies including lung, ovarian and colorectal cancers. Cisplatin was the first approved platinum drug (1978) followed by carboplatin (1989) and oxaliplatin (2002), which together generated annual worldwide sales of approximately $3 billion in 2007. These drugs exert their antitumor activity by binding to DNA and interfering with DNA replication, ultimately leading to cell death.
Despite their impressive activity, platinum drugs suffer from two primary drawbacks. The first drawback is the appearance of undesirable side effects and toxicities. Cisplatin often leads to kidney toxicity, while carboplatin and oxaliplatin often lead to bone marrow and nerve toxicities. The most urgent safety issue is the nerve toxicity caused by the use of oxaliplatin in colorectal cancer, as it sometimes forces physicians to stop the administration of the drug. The second drawback of platinum compounds is the emergence of platinum resistance in most patients during or following treatment. These patients stop responding to treatment after an initial response within several months of initial treatment. Moreover, some cancers are inherently resistant to platinum even before being exposed to platinum drugs. Fortunately, many resistance mechanisms tumors utilize to block the anti-cancer effect of platinum drugs have now been elucidated, and this knowledge will hopefully provide the basis for the development of the next generation of platinum drugs.