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A few months have passed since my last post, as there has been things happening in the biotech world, but nothing 'new' enough to jump on board and get behind. Drug development is a long, arduous process, and clinical trials are the worst. The smaller the diseases are in a population, the longer it takes to enroll, test and then post results.
At PSW, we have been patient investors in MITI (bought by Amgen), CRIS, EXEL, SGEN and many others, and waiting in the wings are CLDX, YMI, and now PGNX. I noted several years ago, that cancer and neuroscience are the final frontiers to conquer, and they remain today where they were then…so time does not change things that fast! Diabetes and cardiovascular diseases are pretty well served with existing therapies, and yes, there will be a few that creep into the space, but overall these diseases needs are met. The hottest areas in pharma today remain small, elusive, and lucrative diseases that demand a premium – cancer and fibrosis.
Fibrosis is another topic, and in the next few months, an article or two will go over some new therapies for fibrosis, which can manifest itself in several different disease types (IPF, kidney, scleroderma, etc). For now, this article will focus on cancer treatments, and more specifically, monoclonal antibodies (mAbs) that have attached to them a chemotherapeutic.
First, a short summary on mAbs and how they work.
Antibodies are used by the immune system to clear pathogens from the body. The antibody protein is in the shape of a Y, where the trunk is the effector region (similar in most antibodies) an the ends of the Y are the variable regions (paratope) that bind the pathogen (antigen).
Antibodies are produced by B-cells that is used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. There are several types of antibodies made for the defense of the body, and they can be read about here.
Scientists figured out how to manufacture antibodies to a specific antigen in the late 1970s, but it was not until the '80s that the use became more feasible. Mouse hybrids were the first antibodies used (called chimeric suffix -ximab), and now there are humanized (suffix -zumab) and fully human mAbs (suffix –umab). Below is a partial list of approved mAb therapies.
1 Waldmann, Thomas A. (2003). "Immunotherapy: past, present and future". Nature Medicine 9 (3): 269–277. doi:10.1038/nm0303-269
With another twist on mAb treatments, companies figured out how to target cancer cells, and then deliver a 'payload' to the cell of chemotherapeutics. Immunogen (IMGN) and Seattle Genetics (SGEN) are two companies who developed the TAP ( tumor-activated prodrug) and ADC (antibody drug conjugate) technologies, respectively. SGEN has been very active in this area, and has licensed their technology out to several other companies including Celldex (CLDX) and Progenics (PGNX).
Celldex (CLDX) – the company has two late stage candidates for the treatment of breast cancer (CDX-011) and glioblastoma (Rindopepimut). Rindopepimut is Celldex's most advanced candidate and being investigated for glioblastoma. The drug is an intradermal injectable peptide vaccine targeted against epidermal growth factor receptor (EGFR) vIII developed by John's Hopkins. In its previous trial, it showed significant progress in overall survival and progression-free survival. However, with the company enrolling patients, there is not a great deal of news surrounding this candidate. CDX-011 (glembatumumab vedotin), in its Phase 2b EMERGE study in patients with glycoprotein NMB (GPNMB) expressing, advanced, heavily pretreated breast cancer, impressive response rates compared to current, available therapies in patients with advanced, refractory breast cancers with high GPNMB expression (expression in e25% of tumor cells). Final data are to be released any time, and taking some profits off the table now. Selling some puts if they pull back is a very wise way to play for a good longer term hold. For a risk on trade, selling the Dec $5 puts and buying the $7/8 BCS for a net 10 c on the $1 spread offers a bit of a risk reward profile that warrants some consideration.
Progenics (PGNX) – the company's main drug (Relistor) is used for relieving the constipation side effects of patients who are taking opioids (e.g., morphine) for pain. While this is a large market, the drug is given by subcutaneous injection, and it was delayed by the FDA (cosponsored by Salix). This delay, while a set back, should only be about 18 months or so. The more compelling case in PGNX's pipeline is their ADC mAb. PSMA ADC, an antibody-drug conjugate ("ADC") therapy for prostate cancer that binds to PSMA, a protein that is abundantly expressed on the surface of prostate cancer cells, as well as cells in the newly formed blood vessels of major solid tumors. The drug that is conjugetd to the mAb is monomethyl auristatin E, the same drug that is used in SGEN's Adcetris (brentuximab vedotin).
In the initial phases of the Phase 1 trail, four of nine patients treated with PSMA-ADC at 1.8 mg/kg showed reduced prostate specific antigen, circulating tumor cells and/or bone pain. Subsequent patients have shown that PSA reductions of 50% or more, and CTC (circulating tumor cells) reductions of less than 5 cells/7.5 ml blood were seen in around 50% of patients at doses of greater that 1.8 mg/kg. While it is early on, the mAb drug complex is compelling enough for a small allocation.
– Pharm
