For part I click here

On top its JAK programs, Incyte (INCY) 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.

Last week, Incyte (INCY) sold over $130M worth of stock and $400M worth of convertible debt in an effort to solve its balance sheet issues. Thanks to the stronger cash position, the company can finally be evaluated based on its promising pipeline rather than its capital structure. More importantly, it will be able to complete a series of business development deals and focus on becoming a commercial stage company.

As I explained in a previous article, the company presented investors with a dilemma. Fundamentally, it had a potential blockbuster with a high likelihood of reaching the market in 2011, whereas financially, it was heading for insolvency, with ~$150M in cash and more than $400M in debt (due 2011) as of the end of Q2. To make things more complicated, Incyte was trying to get a lucrative deal for its lead drug candidate, INCB18424 (424), but the company’s shaky financial position diminished its negotiation leverage. The debt overhang also put pressure on the stock, which prevented Incyte from raising the necessary funds without substantially diluting its shareholders. Consequently, Incyte had to compromise on the terms of the offering or those of the licensing deals.

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.

According to the company, its strengthened cash position will provide at least two years of operations, assuming no additional funds are received. Most of the budget will probably be related to Micromet’s lead agent, blinatumomab, which is expected to enter a pivotal trial in Acute Lymphoblastic Leukemia (ALL) in the first half of 2010.

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 a tricky one.

Incyte’s lead drug is INCB18424 (aka 424), currently in two registration trials in myelofibrosis (MF). Myelofibrosis is a blood disorder in which the bone marrow becomes dysfunctional. MF Patients, who often have enlarged spleen and anemia, suffer from a myriad of symptoms including infections, chronic fatigue, fever and weight loss. On average, patients survive five years from diagnosis as a result of infection, bleeding and organ failure. There are currently no approved drugs for MF and most patients are treated with drugs that alleviate symptoms, but typically have little impact on the course of the disease.

Last month at the ASCO meeting, Curagen (CRGN) presented results for its lead drug, CR-011, in breast cancer and melanoma patients. CR011 had activity in both indications, however, most of the drug’s value should be ascribed to the breast cancer program, which represents a huge commercial opportunity and better chances of approval.

As I previously wrote, the significance of the breast cancer trial is not only in the clinical activity of CR-011, but more importantly, the ability to identify patients who are likely to respond to the drug. By defining the right target population, Curagen could substantially improve chances of approval, shorten development time and enjoy high market acceptance.

This year’s American Society of Clinical Oncology (ASCO) meeting was packed with promising early stage trials, but very few positive late stage trials with an impact on medical practice. The two most important practice changing trials were phase III studies for Eli Lilly’s (LLY) Alimta and Roche’s (RHHBY.PK) Herceptin. These drugs are likely to enjoy a boost in revenues starting from next year, as both demonstrated impressive survival prolongation in lung and gastric cancer patients, respectively. The studies also underscore the paradigm shift in the industry towards personalized medicine, where a drug is given only to patients who have a high likelihood of deriving benefit. This article will focus on Alimta, which was, in my opinion the winner of ASCO 2009.

A new treatment line

Click here for Part 1

Seattle Genetics – Another step towards approval

The ASCO annual meeting, one of the most important events in the pharmaceutical industry will take place in Orlando next weekend. With over 4,000 abstracts to be presented this year, separating the wheat from the chaff is difficult, but below is an incomplete list of intriguing trials that deserve investors’ attention.

Pfizer- personalized medicine at its best

Two weeks ago, Micromet (MITI) hosted its annual R&D day, where it discussed plans for 2009 and beyond. The meeting provided plenty of information regarding the company's technology and drug candidates, but more importantly, it served as an appetizer for next month's EHA meeting.

As a reminder, Micromet is expected to present data from 2 trials evaluating its lead agent, blinatumumab (MT103), in two forms of blood cancer: Non-Hodgkin Lymphoma (NHL) and Acute Lymphoblastic Leukemia (ALL).

Click here for Part 1.

Regulation and competition

Micromet (MITI) intends to launch a pivotal study for blinatumumab as consolidation therapy in ALL patients next year, starting from Europe with a likely expansion to North America. Due to the small market size and the aggressive nature of the disease, the trial should be relatively small and short. For example, Genzyme’s (GENZ) Clolar, which is approved for the treatment of pediatric ALL, got approved based on a single arm 49 patient trial, with objective response rate as the primary endpoint. Although it is common to see approvals based on tumor response in settings where there are no available treatments, the situation with blinatumumab is more complex.

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.

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Undisclosed antibody (Centocor)

Centocor, a wholly owned subsidiary of Johnson & Johnson (JNJ), signed a licensing deal with Morphosys (MPHSF.PK) in late 2000. In the summer of 2007, Centocor promoted one of its programs to phase I trial in solid tumors. Five months ago, it started another trial in an autoimmune indication, idiopathic pulmonary fibrosis (IPF) with the same antibody. Although Centocor did not disclose the identity of the antibody and its target, it seems that the mysterious antibody is CNTO-888, an antibody targeting a protein called MCP-1. Similarly to the two other partnered programs, CNTO-888’s trials are relatively large with 54 and 120 patients planned for accrual in the cancer phase I and IPF phase II, respectively. The phase II is a placebo controlled study.

Morphosys (MPHSF.PK) is one of the most unusual biotech companies, as it breaks three basic rules that apply to drug development companies:

Rule No. 1: Development-stage companies burn cash and therefore must constantly raise capital and dilute existing shareholders.

On Wednesday, Roche (RHHBY.PK) announced positive results from a phase III study evaluating its breast cancer blockbuster, Herceptin, in gastric cancer. According to Roche, the addition of Herceptin to standard chemotherapy “significantly prolonged” overall survival of gastric cancer patients. From a medical perspective, this trial is a great achievement considering the severe shortage of effective treatments for gastric cancer. This is also the first success Herceptin has outside of breast cancer, where it quickly became a cornerstone treatment.

Similarly to the case in breast cancer, the gastric cancer trial (the Toga study) included only patients whose tumors express Herceptin’s target, the Her-2 protein. The idea of distinguishing between patients based on the biology of their tumors has become the standard in many cancer trials, particularly when targeted therapies such as Herceptin are involved. The Toga trial further validates this approach, and proves yet again that homing in on a genetically defined subgroup of patients may decrease a drug’s addressable market, but increases chances of showing a real benefit.

Of all the healthcare companies that took a beating in 2009, Celgene (CELG) seems to be the most undervalued one. Looking at the company’s financial performance and upside potential, it is very hard to understand how a growing biotech company with virtually no potential threat to its leading products is traded at such a low price, a real steal. I typically write about development stage companies, where financial metrics are irrelevant and the focal point is on scientific and medical data. In Celgene’s case, all that is needed is to examine the financial performance and the markets in which the company operates.

The past six months have not been kind to microcap biotech stocks, as it is hard to find a lot of love in today’s market for tiny, high risk, cash burning biotech companies. Honestly, who can blame investors for throwing stocks that offer a distant dream with minimal success rates and heavy spending? Surprisingly (or not), the negative sentiment also presents unprecedented opportunities in the microcap arena, as some microcaps are making tremendous progress, which is not yet reflected in their stock prices.

In my previous article, I discussed the pharmaceutical industry’s race after approved drugs and late stage agents with proof of concept in humans. I mentioned Rigel’s (RIGL) lead drug, R788, as a likely target for collaboration due to its impressive activity, the huge addressable market and the fact it is an oral drug. For the past year, Rigel’s management has been consistently and rigorously claiming it will have a partnership in place during the first quarter of 2009. Although the company has had more than one opportunity to change this forecast, it stuck by its original statement. For example, when new safety data got published last year and worried investors sent the stock down 50% in two trading sessions, many believed that the imminent deal was not going to materialize. To their surprise, Rigel reassured investors the time frame for a partnership remains intact, explaining that none of the recently published data was actually new to potential partners. Then, Rigel appeared in countless investor conferences, the last of which was only last month, promising investors a licensing deal is forthcoming.

Last week, the company announced it no longer expects to have a deal by the end of March. Instead, it intends to wait until it has results from two ongoing trials, due this summer. Deciding to wait until more data is available makes a lot of sense, providing the data is good. Typically, the further a drug gets in clinical development, the higher its value in the eyes of potential partners. The problem is not the decision itself, but its timing, as this kind of decision could have been made long ago. So what led Rigel’s management to suddenly change its mind after a year of expectations build up?

In the pharmaceutical industry, 2008 will probably be marked by the big pharmas’ insatiable appetite for new drugs. Threatened by fierce generic competition, the pharmaceutical giants were not only eager to pay generous acquisition premiums for marketed products, but were also willing to pay a lot of money for investigational drugs with an early proof of concept in the clinic. Two recent examples for this trend are Arqule (ARQL) and Exelixis (EXEL), which recently signed two lucrative deals with Daiichi-Sankyo and Bristol-Myers Squibb (BMY), respectively.

Assuming this trend continues in 2009, it is crucial to identify small and medium companies with candidates whose activity has already been proven in clinical trials. One of the most interesting companies that fall into this category is Rigel Pharmaceutical (RIGL). The company is currently developing a validated drug with blockbuster potential, and is expected to announce major collaboration deal during the first quarter.

In a time when so many biotech companies do not know how they will survive the nuclear winter of 2009, two companies we hold in the biotech portfolio stand out in the crowd. Immunogen (IMGN) and Exelixis (EXEL) are poised for an exciting year, with plenty of events in the coming twelve months.

The two companies have a lot in common. Both are developing innovative drugs for cancer that rely on remarkable basic science, both can generate an unlimited number of novel agents that in turn can be licensed to large partners, and perhaps more importantly these days, both can remain independent of the capital markets for at least two years. Above all, the two companies exemplify how good products and good technologies can still generate tremendous value for investors, even during these economic turbulent times.

Yesterday morning, Arqule (ARQL) announced it had signed two licensing deals with Japan based Daiichi Sankyo. The first deal involved the licensing of Arqule’s lead compound, ARQ197, a kinase inhibitor for the treatment of cancer, with a very broad potential utility. The second deal was a drug discovery collaboration in which Daiichi Sankyo gets access to Arqule’s recently established discovery platform with the purpose of developing kinase inhibitors against two targets. 

The two deals are great news for Arqule because they serve as a validation for both ARQ197 and Arqule’s technology. The licensing of ARQ-197 was a much anticipated event, as I previously wrote here, as it seemed like the best way to unleash the potential of a compound with a utility in so many different indications. Prior to the deal, Arqule was a small company who carried the burden of developing a promising drug in a highly competitive field with limited financial resources. Now, with the resources of a large partner, Arqule can finally advance ARQ197 fast aggressively, without diluting its shareholders.