Hot Watch List (comments).

AGEN (neutral)

"Antigenics (AGEN.O) is also developing a cancer vaccine, called Oncophage, for kidney cancer and melanoma."

"..i do not see buyout...PFE walked away.Why? Because AGEN has a far superior product called a phase 2 trial for newly diagnosed glioma they have 8 out of 8 patients so far cancer FREE..this study will be concluded next year and it is a combination therapy of: surgery plus chemo plus the vaccine."

By agen_follower

Since several sources cited the company Antigenics Inc. (AGEN) as a competitor of CLDX I have decided to compare the science basis of these 2 companies. And why actually company’s pps are so different: AGEN is $0.92 and CLDX is $4.62?

Antigenics Inc., a biotechnology company, develops and commercializes technologies to treat cancers and infectious diseases primarily based on immunological approaches.

I checked AGEN news and they are mostly negative (especially written By Adam Feuerstein)

Antigenics(AGEN_) and its cancer vaccine Oncophage is a two-time loser, having failed phase III studies in melanoma and kidney cancer.

Antigenics did manage to secure Oncophage's approval in Russia in 2008, although it took until this year for a single Russian patient to actually pay for treatment with the drug. European regulators rejected Oncophage in 2009 and the clinical data from phase III studies and post-hoc survival registries is of such low quality that Antigenics can't even approach the U.S. Food and Drug Administration about seeking approval here.

Antigenics continues to pursue Oncophage's development, with data from a phase II brain tumor study expected later this year.
Overall, a dozen experimental cancer vaccine programs have failed phase III studies, according to a list compiled by MD Becker Partners as part of an in-depth cancer vaccines report published recently by the biotech consulting firm.
MD Becker Partners' principal Michael Becker, in his report, identifies two main reasons for why cancer vaccines have a historically high failure rate. First, companies rushed cancer vaccines into the human testing without understanding how they worked on a molecular level. As a result, many early cancer vaccines lacked potency and were unable to provoke an immune response strong enough to fight off tumor cells
Second, drug companies tried to develop cancer vaccines on the cheap. Instead of spending money on robust mid-stage studies to winnow out potential winners from the losers, companies moved quickly into large, high-risk phase III studies, he says.

Well, what about AGEN science?

Platform Technologies

Heat Shock Proteins


Heat shock proteins (HSPs), also called stress proteins, are a group of proteins that are present in all cells (normal cells, cancer cells and infected cells) in all life forms. They act like ‘chaperones,’ making sure that the cell’s proteins are in the right shape and in the right place at the right time which is essential for their function. More recent research has demonstrated that HSPs play an essential role in the presentation of pieces of proteins (or peptides) on the cell surface to help the immune system recognize diseased cells. In carrying out this function, HSPs bind to essentially every peptide in the cell, forming HSP-peptide complexes inside the cell. When a cell has become so sick that it dies, it can in some circumstances spill out all of its contents, including HSPs. This kind of messy, unplanned death is called necrosis and only occurs when something is very wrong with the cell. HSPs release from dying cells send a ‘danger signal’ to the immune system leading to generation of immune responses that can help to get rid of an infection or disease. Antigenics’ use of HSPs as vaccines against cancers and infections is thus intended to mimic and enhance what our bodies do normally to combat disease.

Heat shock proteins in immunity to cancer

The application of an HSP-based therapeutic approach to cancer is supported by seminal research showing that HSPs isolated from cancer cells elicit immunity to cancers whereas HSP preparations from normal tissues do not. Further, the immunity elicited by HSPs was observed to be individually cancer specific. That is, HSPs elicit immunity only to the particular tumor from which they are derived.

Other research has shown that the immune response to the unique, tumor specific antigens is associated with tumor regression and prolonged survival in cancer patients. Collectively, these studies provide a strong rationale for administering cancer vaccines that contain a broad repertoire of tumor specific antigens- with the aim of further enhancing the very type of immune response which appears to be associated with prolonged survival of cancer patients. Such antigens are found in autologous cancer vaccines, like Oncophage.

Heat shock protein mechanism of action

Whether HSP-peptide complexes are isolated from cells or made synthetically, they represent a potent means of activating the immune system. Upon injection into the skin, HSP-peptide complexes interact with the immune system’s antigen-presenting cells (APCs) at the site of injection. APCs express receptors for HSPs, including CD91, leading to internalization of the complexes and migration of APCs to the lymph nodes. There, the APCs re-present the antigenic peptides on their surfaces. This triggers a cancer or pathogen-specific T cell response as well as release of immune system substances called cytokines which mediate other immune effector mechanisms.
The multi-faceted nature of immunity elicited by HSPs has led to their being described as the immune system’s “Swiss army knife.”

In short words, AGEN uses conventional artificial active immunization method to fight cancer.

When an immune system is exposed to molecules that are foreign to the body (non-self), it will orchestrate an immune response, but it can also develop the ability to quickly respond to a subsequent encounter (through immunological memory). This is a function of the adaptive immune system. Therefore, by exposing an animal to an immunogen in a controlled way, its body can learn to protect itself: this is called active immunization.

Active immunization

Active immunization entails the introduction of a foreign molecule into the body, which causes the body itself to generate immunity against the target. This immunity comes from the T cells and the B cells with their antibodies.
Active immunization can occur naturally when a person comes in contact with, for example, a microbe. If the person has not yet come into contact with the microbe and has no pre-made antibodies for defense (like in passive immunization), the person becomes immunized. The immune system will eventually create antibodies and other defenses against the microbe. The next time, the immune response against this microbe can be very efficient; this is the case in many of the childhood infections that a person only contracts once, but then is immune.

Artificial active immunization
is where the microbe, or parts of it, are injected into the person before they are able to take it in naturally.

In the contrary to AGEN, CLDX technology uses some combination of active and passive immunization. CLDX physically link specific antigens to humanized antibodies. These antibodies injected in a patient specifically target the dendritic cell surface (it’s likely to self-guided missile).
Dendritic cells internalize these targeted antigens into specific cellular compartments and then present the processed antigen on the cell surface, thereby initiating the desired immune response.

Passive immunization

Passive immunization is where pre-synthesized elements of the immune system are transferred to a person so that the body does not need to produce these elements itself. Currently, antibodies can be used for passive immunization. This method of immunization begins to work very quickly, but it is short lasting, because the antibodies are naturally broken down, and if there are no B cells to produce more antibodies, they will disappear.
Passive immunization occurs physiologically, when antibodies are transferred from mother to fetus during pregnancy, to protect the fetus before and shortly after birth.
Artificial passive immunization is normally administered by injection and is used if there has been a recent outbreak of a particular disease or as an emergency treatment for toxicity (for example, for tetanus).

Conclusion: CLDX invented a unique method to deliver specific antigens (cancer or other diseases) to antigen presenting cells (APCs) particularly to dendritic cells. Each CLDX vaccine designed to specific kind of cancer or other disease but it's not individual vaccine i.e. any patient with this kind of cancer may be treated.

AGEN uses a conventional method of artificial active immunization. The vaccine is prepared individually for each cancer patient i.e. patients first have surgery to remove part or all of the cancerous tissue, and the tumor tissue is shipped frozen to Antigenics’ state-of-the-art GMP manufacturing facility in Massachusetts. Using a proprietary, standardized, quality-controlled procedure, the product is isolated from the tumor in 8-10 hours. The product is sterile-filtered, packaged in vials, and shipped frozen back to the hospital pharmacy or clinician for use when the patient has recovered from surgery.
The vaccine is administered as a simple weekly or biweekly intradermal injection during an office visit.

Both companies have a strong science basis. However, it's obviously that CLDX science is more innovative than AGEN science. Time will tell which company will win.

The multi-faceted nature of immunity elicited by HSPs has led to their being described as the immune system’s “Swiss army knife.”

"Swiss army knife" against cancer?
CLDX antibodies remember me the Ballistic knife, AGEN is just similar to Swiss army knife. I prefer the using of the Spetsnaz's  Ballistic knife against cancer.