Another Immune Company Play – Immunomedics

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Cancer is a class of diseases in which a group of cells display uncontrolled growth.  Some cancers invade or intrude upon adjacent tissues, then destroy that tissue/organ, and then spread (metastasize) to other locations in the body via lymph or blood.  These three malignant properties of cancers differentiate them from benign tumors, which do not invade or metastasize.  All of these diseases suggest that there will be a need for personalized therapy, as even within a specific type of cancer, there is wide heterogeneity in clinicopathological features.  For instance, leukemia, lymphoma, myeloma, etc are all lymphoproliferative disorders (where lymphocytes are produced in excess) affect one or more different biological pathways that play a role in lymphomagenesis (the development of B cells and T cells).  Over the past year, on focal point of our  investment virtual portfolio has been smaller companies researching and developing treatments for cancer (CRIS, ARIA, ARRY, SPPI, IMGN).  The next small company with some very interesting prospects in the pipeline is Immunomedics.

Figure 1.  Cancer Prevalence.

In our recent past, monoclonal antibodies (mAbs) were discussed in the context of a mid-tiered pharma, BIIB and smaller biotech, Immunogen (IMGN).  These companies will not be rehashed, but to re-emphasize that mAb and biologics are one of the hottest areas in in biotech.  Small molecules have are not the favorites for now (especially in cancer), and that is most likely due to early stage trials, lack of efficacy, or more likely – patent protection, as biologics/mAbs are harder to show equivolance….and thus have the potential to generate cash for years to come. 

(IMMU) based in New Jersey, is primarily focused on the development of mAb-based products for the targeted treatment of cancer, autoimmune and other diseases.  The company has a number of advanced mAbs that can be used either alone in unlabeled or “naked” form, or conjugated with radioactive isotopes, chemotherapeutics or toxins, in each case to create highly targeted agents (think Inmunogen, but different 'targets').  The company has built a pipeline of therapeutic product candidates that utilize several different mechanisms of action discussed below.  The company also owns a stake in IBC Pharmaceuticals, Inc., which is developing a novel Dock-and-Lock (DNL) methodology.  This DNL technology can be used for making fusion proteins as well as a new method of delivering imaging and therapeutic agents selectively to disease, especially different solid cancers (colorectal, lung, pancreas, etc.), by proprietary, antibody-based, pretargeting methods.  Those methods are noted below:

• LeukoScan® (sulesomab) is a murine monoclonal IgG antibody Fab’ fragment labeled with the isotope technetium-99m. The fragment targets NCA-90, found on the cell membrane of graunlocytes (a type of white blood cell). Using a gamma camera, LeukoScan can be used to detect osteomyelitis (a bone infection). LeukoScan is not available in North America, but it has European-wide registration and it is also approved in Australia.
• ImmuSTRIP is an ELISA method immunoassay laboratory test kit used to detect Human Anti-Murine Antibodies (HAMA). Using this kit, clinicians can determine if their patients have preexisting HAMA or have developed HAMA due to recent treatments with murine monoclonal antibodies. ImmuSTRIP is a simple to use test kit that provides results in as little as one hour and is available for use by reference laboratories.
• With IBC Pharmaceuticals, IMMU is developing TF-2, a bi-specific mAb targeting carcinoembryonic antigen (CEA) and histamine-succinyl-glycine (HSG), constructed using the Dock-and-Lock (DNL) protein engineering platform technology as a potential PET tracer for the diagnosis of cancer.  Without going into a ton of detail, this is an interesting twist for finding and/or treating solid tumors.  Abstract is here.

The 'detection' segment of IMMU is interesting, and could be lucrative after a very long run, but it is the pharmaceutical wing that is garnering some attention.  Much like Immunogen, IMMUs combination of a mAb with chemotherapeutic is the next craze in this area. Figure 2 below shows the company's pipeline, and a brief description is below that.

Figure 2. Clinical Pipeline of IMMU.

1. Epratuzumab (IMMU-103) binds to the glycoprotein CD22 of mature and malignant B-cells, which it destroys by antibody-dependent cell-mediated cytotoxicity. Epratuzumab is being developed for the potential iv treatment of non-Hodgkin's lymphoma (NHL) and acute lymphoblastic leukemia (ALL). Licensee UCB is developing the drug for the potential treatment of autoimmune disorders, including systemic lupus erythematosus (SLE). Data are not due out until 2014 for SLE.  Competition in this space is heating up, as Pfizer, Medarex, and Crucell NV all have competing mAbs in the clinic.  Epratuzumab is the furthest along in PIII.
2. Veltuzumab (MMU-106) is a humanized anti-CD20 mAb for the potential iv or subcutaneous treatment of chronic lymphocytic leukemia (CLL) (think rituximab – a $6B drug).  Experts agree that the CD20 antigen is an ideal therapeutic target as it does not 'shed' into the bloodstream, does not undergo internalization, is expressed almost universally in malignant B-cell lymphocytes and is not expressed in non-hematological cells.  Unlike rituximab, veltuzumab will be less likely to induce formation of human anti-chimera antibodies and infusion reactions than chimeric compounds such as rituximab, allowing for safer and shorter IV administration; Nycomed licensed the drug for the development of immune thrombocytopenic purpura (ITP) and investigating it for rheumatoid arthritis (RA).  Competition exists for the anti-CD20 area, as GSK is developing ofatumumab, while Roch/BIIB has afutuzumab (one reason I really like BIIB).
3. Clivatuzumab (IMMU-107) is an yttrium-90-linked humanized PAM4 monoclonal antibody for the potential treatment (and SPECT imaging) of pancreatic cancer.  The challenge in pancreatic cancer is early diagnosis, before the disease has spread and treatment options become limited. To that end, the IMMU has recently developed a new serum-based enzyme immunoassay (ELISA) employing clivatuzumab that has a sensitivity of 62% for detecting stage-1 pancreatic cancer (disease confined to pancreas), 86% for stage 2 disease, and 91% for stage 3/4 (local and distant spread) cancers (press release here).  At the 2011 Gastrointestinal Cancers Symposium, IMMU presented that clivatuzumab tetraxetan, labeled with yttrium-90 (Y-90) plus low-dose gemcitabine at 200 mg/m², extended median overall survival (OS) to 11.8 months, more than double the 5.4 months OS in patients treated with a single cycle. Increased Y-90 doses also improved responses; patients receiving a dose of 12 mCi/m² or higher once a week for 3 weeks reporting a median OS of 8.0 months versus 6.0 months at doses of  9 mCi/m² or less, once a week for 3 weeks. A pacreatic cancer cell is below.

4. Milatuzumab (IMMU-115; IMMU-110) is an iv humanized anti-CD74 (hCD74) monoclonal antibody, for the potential treatment of multiple myeloma (as MyelomaCide), non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL), the company is investigating the drug for malignant melanoma (as MelanomaCide) and mantle cell lymphoma (MCL). The only difference between 115 and 110 is that 110 has doxorubicin conjugate to the antibody, therefore packing a 1-2 punch. 

The latter 3 are all in Phase 2 clinical trials, and data should start coming out by years end.  Further, the ASCO conference is coming up in Q2, and thus any data that may be 'leaked' would benefit the company (and the stock price).  Therefore, buying now and selling on the news is the way to play this one, and in member chat is where the trade will be initiated. 

I currently do not own any IMMU, but may initiate a trade in the coming days.