We have batched and presented your questions to Dr. Moro. Neither the questions nor the answers were edited by AGORACOM:

A new question has been posted: (Aug 6)
Company: BioCurex
From: great-grandma
Title: Publishing in a medical journal
Body:
Do you have any plans to publish something in scholarly journals? I know you couldn't when you were waiting for patents to be granted or filed, but what about now? If not, how do you hope to gain the acceptance of the medical community?

Yes, we are writing several papers to be submitted to peer-reviewed journals. The first two to come out will be on early breast cancer detection and the other relates to early detection of prostate cancer and the significant increase RECAF lends to PSA in terms of specificity. As was announced this week, PSA is no longer recommended for men below 75 years of age because the risks of doing the biopsy as well as the stress on the patient outweigh the benefits. This is mainly because about 2/3 of the biopsies show benign lesions. From the data obtained in the blind study to be submitted for publication, combining RECAF with PSA can reduce the number of unnecessary biopsies. This way, the organ specificity of PSA can be paired with the cancer specificity of RECAF in what looks like a win/win situation.

A new question has been posted: (Aug 5)
Company: BioCurex
From: Longterm31442
Title: amendment
Body:
question to DR MORO. don't you need to amend the incorrect wording in the 8K ? is there not a deadline for that? like today??

The 8K is being prepared and will be filed.
View the message: http://www.agoracom.com/ir/Biocurex/...

A new question has been posted: (Aug 4)
Company: BioCurex
From: opportunityknocking
Title: Collaborations with pharmaceutical companies?
Body:
Are there plans to team up with any pharmaceutical companies in the future to find a cure or reduce side effects of current therapies or are the plans to go it alone? Our goal should be to enhance whatever therapies are being used today.

Most certainly, but before we can do that, we need more data because otherwise
(a) the value of our technology will be leveraged down by the other part based on the possible risk that the positive but very preliminary results we have obtained do not result in a commercial product and
(b) there will be a great deal of work that will be done after a collaborative agreement is signed. The inventions resulting from that work will be joint inventions and that could prevent us from licensing the finished technology – which is the really valuable one - to a competitor of the other party. One of the main reasons we sought funding last year was to advance the work on the therapy side to then approach possible licensees. We then needed to concentrate our present efforts on the blood tests which just resulted in a delay to go back to the therapy applications.
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A new question has been posted: (Aug 4)
Company: BioCurex
From: dude2
Title: Press Release Dated June 12, 2008 (Elisa Recaf Blood Test)
Body:
You stated in that article, each clinical lab will be responsible for obtaining approval from the regulatory agencies in its country.
Could you answer the following four questions:
1.) How much would the approval process cost a lab in the three largest markets you are currently pursuing.
It depends on the way it is done: If we are dealing with an established clinical lab (as is the case in one of those locations), they will absorb the cost of the work and we’ll absorb the cost of the reagents (which we would prefer not to disclose for obvious reasons). On the other two markets, the estimations are between $25,000 and $100,000, but there is no RECAF approving precedent anywhere and those who have obtained approval for traditional cancer markers are not sharing that information.
2.) How long does it usually take for approval once the necessary paperwork has been submitted to the approval agency by the lab
Usually between 3 months and 2 years, but it might be shorter and in some particular cases, it might take longer.
3.) Why would the labs in those countries be willing to take on the burden of funding the approval process.
Because they would get an exclusive license (subject to yearly quotas) in that country, because the cost to them is not too high and most importantly, for the same reason we received down payments from our licensees; that is, because there is a great deal of money to be made.
4.) Won't the Elisa Recaf blood test compete directly with the automated test being developed by Inverness and Abbott making Recaf less attractive to those two companies.

Each format has its own market. In large clinical labs, mostly in developed countries, using a manual assay is not cost efficient and therefore it is better for them to use an automated instrument. The manual assay market represents a small fraction of the market to a company that sells billions/year, such as our licensees, but it is very significant for us. In any case, our licensees did not mind signing agreements with the manual assays restrictions and therefore, if they did not have concerns then, why would they have them now? Before someone asks the follow-up question to these comments, intermediary labs, who have the automated instruments in place might want to start using manual tests and then, as our licensees bring their products to market, and these labs receive more and more RECAF tests orders, they might switch from the manual to the automated tests. It matters not to us; we shall receive royalties one way or the other.
View the message: http://www.agoracom.com/ir/Biocurex/...

A new question has been posted: (Aug 4)
Company: BioCurex
From: golf game
Title: Prostate cancer studies
Body:
Dr. Moro, I have been a share holder since the initial Abbott news in 2005 and I have continued to hold believing in the product as I watched the investment evaporate. I was unaware that conflicting results for prostate cancer have been published. The first study conducted in November 2004 was excellent with about 90% sensitivity and no false positives. The second study published was in May 2006 with results as low as 68% sensitivity and 3% false positives.
The ISOBM results are very confusing using ROC and C/N ratio. Abbott stated the C/N ratio of 1.3 was not high enough for commercialization.
1.How can there be such a huge difference in the results of the studies run with the same test?
2.Who conducted each of those studies?
3.Can you restate those results in terms of sensitivity and false positives we understand?
View the message: http://www.agoracom.com/ir/Biocurex/...

This question requires many hours and pages to be answered properly to a non-scientific audience. I will do my best to keep it simple but that requires some faith on behalf of the reader.
1) Variation of results: The literature shows that the values or sensitivity and specificity vary from one study to another when using any marker. This is due to many reasons:
(a) Samples are not treated equally. Some are heated to destroy viruses, others are not, the tubes in which they are collected might not be the same (and they contain chemicals that are proprietary and kept secret by the manufacturer), the clotting time before the serum is collect varies from 10 minutes to overnight, etc. In some cases we can partly control these variables, in other we cannot, particularly when we are using commercial serum samples.
(b) The sensitivity and specificity are a function of the selected cutoff value: If we choose a 4.0 ng/ml cutoff for PSA and we have a number of patients with benign lesions and some with prostate cancer, we shall have some cancers that are above and some cancers below. Sensitivity is the percentage of cancers that fall above the cutoff value. Also, we’ll have some normals or benigns below and above that cutoff value. Specificity is the percentage of normals or benigns that are below the cutoff value. If instead of 4 ng/ml we used 2.5 ng/ml (as many experts advice), then we would catch a few more of the cancers, thus increasing the sensitivity, but we would be catching a lot more normals or benigns thus decreasing the specificity. If, on the contrary, we used 10 ng/ml as the cutoff value then we would have few benigns above it thus increasing the specificity, but we would also have many cancers below 10 ng/ml thus reducing the sensitivity. In summary, if we change the cutoff value, the specificity and the sensitivity change. Since the ROC curve is usually not symmetrical, a lowering of 10% in specificity does NOT mean an increase of 10% in sensitivity. An easy way to determine the cutoff value is to find the one that yields the highest accuracy; that is the percentage of times the assay gets it right (the cutoff with the highest sensitivity and specificity combination). However, the cutoff value is chosen on a great deal of considerations, not only mathematical ones. For example, a physician might want to have the highest sensitivity to catch cancer as often as possible, while a health administrator might want the highest specificity in order not to spend money in diagnosing false negatives.
(c) As we advance in developing the technology, our results also vary. Sometimes, mandatory practical considerations might result in an assay that performs a little less than ideal. Chemiluminescence performs slightly better than ELISA, regardless of the test, but if the client has an ELISA reader and does not have a chemiluminescence reader, then he or she will use ELISAs…
(d) A small difference (3% -10%) cannot be considered as significant with the number of samples tested.
2) The 68% sensitivity is on Stage I and II, which is almost phenomenal. The sensitivity of PSA for the same samples, at the 97% specificity level (same as for RECAF) was 11.5%. If we used the 4.0 ng/ml cutoff for PSA in those samples, the sensitivity is 71% and the specificity is 40%. If we then use the RECAF cutoff that yields that same 40% specificity, the sensitivity increases to 92.3%.
3) The question reads: “Abbott stated the C/N ratio of 1.3 was not high enough for commercialization.”, which is not exactly what the abstract reads: “We developed a non-radioactive RECAF CIA assay that separates multiple types of cancer from normal sera with a C/N ratio ranging from 1.3 to 1.7. Our future studies will focus on increasing the cancer/normal ratio to create a manufacturable RECAF CIA assay”. (a) If it is assumed that Abbott wrote the abstract, then the words: “We developed a non-radioactive RECAF CIA assay that separates multiple types of cancer from normal sera…” should be regarded in the same fashion (I am not at liberty to comment on who wrote the abstract). (b) The C/N ratio is just the average of the readings of the cancers divided by the average of the readings of the normals. Of course, the higher the ratio, the better, but not in relation to the performance of the test, but rather to make the assay more “solid”. Let us suppose that we have a set of RECAF Units readings for cancer patients and for normal patients. We have a C/N= 3. We then add to each RECAF value an arbitrary number. The discrimination of the assay will be exactly the same as before, but the C/N will be lower. Once we got the results, it is irrelevant how much we add, the discrimination will always be the same, even if the C/N = 1.00001. In a real assay, the added number comes usually in the form of background (in general due to non-specific binding of the reagents to the tubes or plastic plates where the reaction takes place). The effect is the same as adding a number, because the background is constant, but in any biological assay, there is always error and that error also applies to the background. If the C/N = 1.00001 and the pipetting error is 1%, then the discrimination will suffer, because the number that is added is not constant and in this absurd example, it is higher than the actual RECAF signal. In realty things do not get that bad, but it is a good idea to reduce the background as much as possible.

The C/N value also depends on the range of the instrument used: In chemiluminescence readers, as well as in radioactivity counters (used for RIA), the range is huge, while in ELISA, Lambert’s law states that a 2x increase in the color being produced results in 4x more color intensity. This makes readings over 3.0 optical density units (O.D. Units) practically impossible. Thus, ELISAS will always have a smaller C/N ratio independently of how good the discrimination might be.

The important point to keep in mind is that what defines the quality of an assay is NOT the C/N ratio but rather the sensitivity and specificity, which represents its ability to discriminate cancers from normals.

We have improved upon those results and currently have C/N ratio of 4 to 6 in chemiluminescence.

3) Q. How can there be such a huge difference in the results of the studies run with the same test?
The difference is NOT huge for an assay that was being developed. It is within expectations if you consider that in one case we had early stages and in the other we tested all cancers together. We never received any comments from our licensees or other scientists in congresses on this point.

4. Q. Who conducted each of those studies? We did some of them in BioCurex and some of them were done in Abbott’s facility.

5) The comments in this and the other forum comparing the area under the curve with the sensitivity and specificity values are inaccurate. The topic is rather involved mathematically to discuss it here. An excellent explanation of how ROC values can be found at http://en.wikipedia.org/wiki/Receive... .

A new question has been posted: (Aug 2)
Company: BioCurex
From: dude2
Title: Feature Presentation on Canadian Station
Body:
Another poster (Burritoman) pointed out today he and his wife vaguely noticed part of a newscast on his local news channel, staing they were doing a feature segment on a Canadian company that detects cancer by a simple blood test. Can you tell us if that company is Biocurex? If so, when does the broadcast air?
View the message: http://www.agoracom.com/ir/Biocurex/...

BioCurex is not scheduled to appear in the news at this time.

A new question has been posted: (July 31)
Company: BioCurex
From: opportunityknocking
Title: Dr Moro, this question is for you
Body:
Do you have a poison pill in place at this very moment, and if not, don't you think you are leaving this company very vulnerable?
View the message: http://www.agoracom.com/ir/Biocurex/...

There are no poison pills at this time. It is reasonable to think that if the sudden sale of about 1M shares produced a significant drop in the share price, the purchasing of the millions it would require to take control of the company would result in a significant rise in the price. This however is purely speculative. So far, we have not received any indication that there is an interest to buy out the company. My personal opinion is that an event of this magnitude should require a vote of the shareholders.

A new question has been posted: (July 30)
Company: BioCurex
From: biotech bonanza
Title: Minimum royalty payment from Abbott
Body:
Since this question is being bantered about on IHUB, what happened to the 2008 $50,000 minimum royalty payment received from Abbott? Was it sent back to Abbott as part of the amended agreement and if so, for what reason? The company cannot just return money to Abbott for no reason.
View the message: http://www.agoracom.com/ir/Biocurex/...

But there is a reason, and a good one, in the form of the amendment we signed before the money was due. This does not mean that they paid and we returned the money, nor does it mean otherwise. We are NOT prepared to disclose our discussions with Abbott on the subject any further than what we have done so far, which we consider is far more than the subject deserves. There seems to be a fixation on this topic with speculations running wild about what happened and what did not happen; most of them fueled by individuals whose job is to create doubts about the company. We cannot and will not comment further on this topic.

A new question has been posted: (July 29)
Company: BioCurex
From: i_invest_utrade
Title: Patent Filed Where?!?
Body:
I am a fool or did I completely miss where the latest patent was filed?
The press release did not state where the patent application was filed.
Is this a US, Canada, China, Japan, Russia, or European patent application?
Thank you.

You are not a fool. The patent was initially filed in the USA. The place of filing is of little consequence if the application is moved into the Patent Cooperation Treaty.

A new question has been posted: (July 29)
Company: BioCurex
From: dude2
Title: Possible Take-Over
Body:
Do you foresee a possible hostile take-over by Inverness which has been the case with other Biotechs in the past. Do you have a so called poison pill to prevent this from happening. This topic has been discussed several times at I-Hub. Sure would be nice if you could put this concern to rest.
View the message: http://www.agoracom.com/ir/Biocurex/...

See previous comment

Dear Dr. Moro: (July 29)

We read your recent press release and noted your comment about the Japan patent.

Could you elaborate a bit for us as to what was the nature of the "unanticipated resistance to approval" there? And why your new patent application necessitates you

This would be for attribution in our executive newsletter, the world's leading management publication on Japan.

Thank you
I am unsure of the meaning of the last portion of this question. The original patent was written for the USA patent office where it was first filed. The same patent was then filed, via the Patent Cooperation Treaty (PCT) to many other countries. We did not have the resources, at the time (this is pre-BioCurex) to file customized applications. Patent law differs from one country to another, and as a result, the claims that have been approved and granted in the USA, Russia, Australia and the European Union, among other countries, were not accepted by the Japanese Patent Office. We could have appealed their decision but we chose to drop it in favor of the patent. Without getting into the confidential detail, it should be noted that our licensees still pay royalties (albeit reduced) for sales in countries with pending patents, which will happen as soon as the PCT filing takes place or in countries with no patents. In some cases, a reduced royalty is still due even in countries with no granted or pending claims.

In reading all of these questions and many more posted here and elsewhere, I have the impression that the sudden and unwarranted drop in the price of the stock has everybody questioning and doubting everything we have achieved. The assay works exactly as good when the share price is $0.90 as when it is at $0.25. Rather than answering questions that have been clear for months or year, Management and other shareholders should instead question those who have sold or short sold massive amounts of shares on their motivation to do so. In particular, we should be asking the motivations behind those who systematically bash the company and its achievements. They do not do it openly, they are too cowardly to do that and of course, it would never happen if they had to use their real name, as I do. Instead, they systematically seed doubt, communicate via innuendos.
So that we set the record straight, this is what we have achieved in the past 2 years:
October 17th, 2006: Independent results support the use of BioCurex technology for Gastric Cancer

October 25th. 2006: BioCurex presents new format for blood test detection of cancer with results superior to PSA

December 7th, 2006: Biocurex Enters Collaboration Agreement With Largest Cancer Research Center in Russia (they have been providing us with samples, they have presented results with us in congresses ever since)

June 5, 2007: BioCurex Reports Initial RECAFTM Cancer 'Rapid Test' Results.

September 18, 2007: BioCurex Presents RECAFTM Point-of-Care Test Results at International Cancer Congress

September 20, 2007: BioCurex and Abbott Jointly Present RECAF Results at International Cancer Congress

January 9, 2008: BioCurex Licenses RECAF Technology to Inverness Medical Innovations

March 20, 2008: BioCurex Announces Amendments to Licensing Agreement We got the manual ELISA rights out of the semi-exclusivity, so that we can sell them or license them to as many clients as we want (they are excluded them from the semi-exclusivity with Inverness also). We increased our royalty, and most importantly, we regained the ability to terminate the agreement if we feel it is in our best interest. Not such a bad deal as some perceive it.

March 25, 2008: European Patent Office Grants Patent for BioCurex's RECAF Blood Tests

May 28, 2008: BioCurex develops NEW format for its RECAF cancer blood test. Results confirm its accuracy.

Dr. Ricardo Moro.