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Analysis:  In war against cancer, progress is in the eye of the beholderSharon Bagley, Monday Jan. 7, 2013.  Reuters

"We don't look at this as progress," said Fran Visco, president of the National Breast Cancer Coalition, of the new numbers. "This is such incremental improvement, when you look at the decades of investments, the cost of treatments, the number of researchers and journals, and then at the number of people who die ... well, we are clearly doing something wrong,"

The “one-size-fits-all” biotech phenomenon:

The above quote by Fran Visco is a fair evaluation of the results of the current status and mindset applied to discovering new, safe, and specific therapeutics for cancer treatment. 

Still today, our current approach is to set up experiments or methods that allow us to find the “one-size-fits-all” drug/target and we routinely fall far off that mark finding antibodies that show minor responses in patient populations (12%-30%).  While we start off with those good intentions, it’s more like “we’ll-take-whatever-we-can-get”, focus on that, and disregard the larger patient population of which the drug has no effect. 


Why is this the approach of choice?  It’s purely for financial reasons.  The current model says that if you find a single antibody that serves up to 30% of a given patient population (the highest attained so far with a single drug) of a given size, you’ll ensure minimally over a $billion in revenue and great returns for your shareholders.  The sub-par antibody therapeutics that are currently being used to treat patients took anywhere from 8-10 years to go from discovery to the market.  And today we are still doing the same experiments with variations thereof to find that elusive single antibody that has the greatest efficacy.  Simultaneously, malignancies of unmet medical need in small patient populations are being passed over and never receive the attention of the new modern discovery tools simply because of market size.


What is wrong with this approach? If the best anti-cancer antibody has a response rate of 30% (not “cure” rate - a response rate can consist of simply giving a patient another two months to live), then that means that our oncologists are minimally sending 70% of that patient population home to spend their last remaining months saying their good-byes.  When they are refractory to all of the approved small molecule toxins that nearly kill the patient while knowing upfront to be ineffective, and/or they have gone through the handful of antibodies already approved or in trials yet are being blindly tried in off-label uses, - they are all sent home to die. 


Personalized medicine and antibodies:  Treating unmet medical needs in real time

Because of the vastly more efficient process of BLAST and it’s usage for novel target/epitope discovery for targeted antibody therapeutics, North Coast is engaged in the search for antibodies that have the broadest effect within a given tumor group - like everyone else.  But we differ not only in the quality of the approach which should lead to superior therapeutics, we differ in that we acknowledge that this process takes time and money to perform this search efficiently.  Thus, rather than ignoring the people sent home to die while we take 8-10 years to find competent partners willing to take on this endeavor, we will take advantage of the tools that we now have available to us (BLAST) and the knowledge attained of basic mechanisms of antibody anti-tumor efficacy, and apply them directly to the patients who need them most - the forgotten 70+% and patients with tumors that are rare and in markets too small to raise the interest of those with access to the best discovery-based tools.


Tumor types that are most suited for rapid targeting via BLAST:

Any malignancy where the normal tissue of origin is no longer present in the patient is an ideal candidate for this rapid approach.  Tumors whose origins are, for example:  ovarian, prostate, thyroid, sometimes breast and colon are easily targeted with antibodies that are tissue-specific.  If the primary tissue of origin has been removed, then these same antibodies are actually tumor-specific by definition - making them ideal therapeutics for tumor targeting and clearance.  Additionally, multiple antibodies can be administered which increases the likelihood of ADCC/CDC tumor destruction.

Thus, when patients have failed all therapeutic options and are given notice that they have ~6 months to live, we feel that within 3 months time, they can be given a fighting chance at life.


Requirements?:

  1. When a patient has surgery to remove either the primary tumor or metastatic tumor or both, that a portion of this be sent to North Coast for immunization and possibly screening if enough sample is attained

  2. The patient needs to be treated while white blood cell counts remain at  healthy numbers.

Tumors that exist in patients where their tissues of origin still exist (ie. such as lung tumors, neuroblastoma, etc), traditional BLAST is being used to find antibodies that differentially detect these tumors vs normal cells.  While it’s possible to do in the time frame of a patient’s last months, the probability of finding this antibody in a timely manner is lower, but not impossible.

"The biggest obstacle" to a true war against cancer, Watson wrote, may be "the inherently conservative nature of today's cancer research establishments." As long as that's so, "curing cancer will always be 10 or 20 years away."  Sharon Begley | Reuters Jan 9, 2013

Why is it possible to use antibodies as personalized therapeutics now?

  1. Speed and Technology:

  2. To go from an immune/titer-positive animal to cell-surface-binding recombinant antibodies takes as little as 14 days.  Time lines like these are unheard of with any other prior technology

  3. Humanization software and synthetic gene production have greatly enhanced the speed of obtaining clones for antibody transfections (7 days or less)

  4. Selecting tissue specific antibodies from small scale expression systems can be performed in about 2 days using tissue microarrays

  5. Improved expression constructs for antibodies enables economical scale up of confirmed tissue-specific antibodies.  Rather than 2000 liter reactors, each antibody is made at sufficient amounts for treating one person using 2-5 liter spinner flasks (7 days or less).

  6. Today, millions of people have received antibody therapeutics and thus formulation of antibodies are now standardized and routine along with administration.


  1. Practical knowledge of therapeutic antibodies:

  2. Antibodies have been validated as cancer therapeutics

  3. Basic mechanism of action:  ADCC and CDC - antibodies targeting tumors today using IgG1 isotypes are efficacious due primarily to ADCC/CDC

  4. Antibodies intrinsically have NO toxicity - you have millions in your body.  The targets they bind determine safety profiles - today, none are directed specifically at the tumor.

  5. Millions of people have received antibody therapeutics to date and efficacy is shown in some patients receiving a single type of therapeutic antibody


  1. Unique business model of North Coast Biologics:

  2. North Coast possesses a “large company / big pharma” technology in a small, non-venture funded company

  3. Enables full execution and deployment of technology in areas no venture funded company would enter due to risk, small market size or small ROI

  4. Not one step of the cycle above hasn’t been done with exception of the dramatically reduced time of taking a discovered antibody into a patient and the manufacturing step.  Rather than 2000 liter preps, we are making 2-5 liter preps for amounts needed to treat  one patient’s tumor. 

  5. Unlike the current protocol of a patient receiving one antibody for a 15% response rate, we will be able to give multiple tissue-specific antibodies to take full advantage of ADCC/CDC killing of tumors.

  6. With the capabilities we’ve built and the validation of antibodies in fighting cancer, we feel morally obligated to provide a fighting chance for the ~80% of cancer patients who are sent home to say their final good-byes. 



For oncologists interested in participating:

This is a new process that is being pursued under various state and federal guidelines; however, the following points should be considered:

  1. Antibodies have no intrinsic toxicity - the only thing toxic about an antibody is the target that it binds

  2. The mechanism of current anti-tumor antibodies work via ADCC (85% of the activity of Rituxan and Herceptin occurs via ADCC and Rituxan patients often relapse with lymphomas that over express CD55 which suggests a role for CDC in killing these cells)

  3. The current weak response rates are due to using only one antibody to fight the tumor.  North Coast will use multiple antibodies to maximally tag the tumor cells for ADCC killing.

  4. As the patient’s oncologist and via approval of the patient, it is imperative that when primary tumor or metastatic tumor(s) are removed surgically that a significant freshly resected portion be sent to the labs at North Coast for preservation and preparations for immunization/antibody generation and screening (where possible).

  5. Emergency IND - this program by the FDA is a possible mechanism for administration of North Coast’s tumor reactive antibodies.

  6. This protocol is for speed.  When patients are told that there is nothing else left, all we need is at least 3 months to generate the tissue-specific/tumor-specific antibodies.  Depending on the approach taken, North Coast will administer the antibodies via outpatient-like administration and monitoring.

BLAST and personalized medicine

“Absolutely no patient should be sent home to die from a tumor where the normal tissue of origin is no longer present.  These tumors are easily targeted with antibodies.  They don’t have to be tumor specific - just tissue specific with the latter being a very low hurdle.”

Antibodies & Personalized medicine