What is the expected result of the treatment?

The expected result is destruction of all cancer cells and the patient being cured.

How early will the treatment take effect?

The Ambrego treatment is designed to maximize the likelihood that the drugs will be effective from the start.

That the right cells are being targeted is shown by a version of the drug that makes the cancer cells visible on MRI. The versions of the drug that actually treat the cells detect the cells in the same way. The Ambrego Labs have by then already tested in-vitro on the patient's cancerous cells sample that the active ingredient these drugs use actually works.

After administration, the drug's effect in destroying cancer cells is detectable in blood tests within days. The effect is clearly visible in MRI within the first few weeks.

Is the treatment given in parallel with conventional chemotherapy or as monotherapy?

The Ambrego treatment is a full replacement for conventional chemotherapy that works for most cancers and stages of cancer. It is safer and more effective than conventional chemotherapy, according to data from tests and treatments already performed.

Even though this is the case, we recognize that conventional chemotherapy is established and proven, while our treatment is not. The safety profile of conventional chemotherapy is well known, and although it has many side effects, it will take a very long time to fully replace conventional chemotherapy.

However, even when a patient undergoes conventional chemotherapy, it is often not known or even highly unlikely that chemotherapy will cure the patient. It is often given with the clear intention of merely prolonging the patient's life. It is precisely in these cases that it makes sense to add the Ambrego treatment, which is more targeted than conventional chemotherapy and can turn palliative chemotherapy into an effective treatment that cures the patient.

Is there a risk of cancer recurrence? How can you be sure that you will be targeting and treating all cancerous cells?

The risk of cancer recurrence remains if the DNA mutations targeted are DNA mutations that occurred in a later generation of the cancer cells.

To avoid this, it is important to take the trade samples at the correct locations. For example, if cancer cell samples are taken from the original tumor, the DNA mutations will also be present in all derived tumors. Metastatic cancer will therefore be completely treatable.

Also, the same precautions which make sure that the treatment has the correct effect including reviewing the targeting in-vitro and in-vivo also reduce the risk of cancer recurrence.

How expensive is the treatment?

The cost of an experimental animal treatment is in the range of 30,000 USD to 100,000 USD, depending on the effort and precautions taken. The cost of a human n-of-1 study with the necessary safety precautions and including costs for external parties start at a few 100,000 USD.

However, we take the patient's financial situation into account in our offers wherever possible. We also cover part of the costs as long as the treatment is experimental.

Why does the treatment work for all cancer types and also humans and animals alike?

Conventional cancer drugs do not act on the actual cause of cancer, which in the vast majority of cases is DNA mutations, but on the changes in the cell caused by these mutations. These are often cancer type specific and often species specific.

The Ambrego drugs act directly on the DNA mutations with their own proteins (the tools of the cells), which are delivered to the cell as part of the drug. All animals and humans share the concept of DNA as the building instructions for the cell.

Only the proteins expressed to stop cell growth or destroy the cells differ from species to species, but because of the toolbox-like nature of Ambrego technology, the drug can be modified to work in a different species within a day.

Why is it important to have separate drugs to stop cell growth and destroy cells?

Interrupting cell growth is the key to cancer treatment that does not stress the patient's body. If this does not happen, cancer drugs must be very aggressive and destroy more cells than have grown through the tumors in the body just to reverse the cancer's effect.

On the other side, actively destroying cells is the key to curing the patient in a controlled fashion. On the other hand, active destruction of cells is the key to controlled healing of the patient. This is particularly important in cancers, where merely interrupting cell growth has proven insufficient as in these cancers conventional chemotherapy, which only interrupts cell growth, only prolongs the patient's life here, but does not cure him.

Why is targeting one or a few DNA mutations enough to treat all cancer cells, even if they are spread throughout the body?

Tumors arise from a single mutated cell, accumulating additional mutations as they progress. Even when tumors become metastatic, they keep the mutations from the original mutated cell.

The Ambrego treatment targets mutations that are common to all cancer cells, i.e., that have arisen from the single mutated cell. Each of these mutations separates healthy cells from cancerous cells and can be used to target the cancerous cells independently of the other mutations.

In the rare case of multiple individual cancer developments in the same patient, multiple DNA mutations need to be targeted, which is also possible with the Ambrego technology by adding multiple guide RNAs.

Individualized cancer vaccines often target 20 different mutations (e.g. BioNTech). Why is one in case of Ambrego’s treatment superior to 20 in case of individualized cancer vaccines?

Individualized cancer vaccines target multiple mutations because there is no guarantee that they will be effective in targeting a specific mutation.

Cancer vaccines do not act on the DNA mutation itself, but on the so-called "neoantigens", the proteins that are formed when the gene with the DNA mutation is expressed. However, there is no guarantee that the gene will be expressed and thus that the neoantigens will be formed, nor is there any guarantee that the neoantigens will have a surface sufficiently different from the original protein for the vaccine antibodies to distinguish the two.

The Ambrego drugs on the other hand actively detect the DNA mutations by binding to them directly, and this binding results into the active ingredients being expressed in the cancerous cells. While multiple mutations can be targeted with the Ambrego treatment by using multiple guide RNAs, this is not required for efficacy.

Does the Ambrego technology modify the patient’s genes in any way?

No. None of the components of the Ambrego drugs is able to modify DNA. Even the Cas9 proteins are mutated deactivated Cas9 (dCas9) proteins that are no longer able to cleave DNA.

CRISPR-Cas9 proteins are known to have off-target events. How do these affect the treatments?

The Ambrego technology incorporates the knowledge gained from years of research on these technologies at institutes around the world.

All necessary precautions have been taken to increase the likelihood that the drugs will only be active in cancer cells. These include the use of dCas9 versions that have a very high specificity, sufficient to bind only on DNA with the cancerous point mutations. In addition, two dCas9 proteins are used to reduce the possiblity of off-target events even further.

Overall, this results in the drugs having a very low probability of attacking healthy cells, nowhere near the probability of chemotherapy attaching healthy cells.

What about negative immune system reactions to the drug?

The occurrence of negative immune system reactions depends on the quality of the drug administration method. With modern methods of administration, negative immune system reactions should not occur.

How would you rate the efficacy of Ambrego treatment compared to other cancer drugs?

Because Ambrego drugs work with an active in-cell system that is delivered into the cell as part of the drug, we can extensively optimize this system to achieve exceptionally high efficacy. We will continue to do this during the experimental animal treatments and human n-of-1 studies.

Does the efficacy and safety profile of Ambrego treatment differ from patient to patient?

Due to the toolbox-like nature of the drug, we do not believe so. This is to be proven in the first animal treatments and human n-of-1 trials.

Are there any side effects? If so, what are they like?

The Ambrego drugs are extremely targeted, and the correctness of this targeting is extensively tested for each patient with different versions of the drug before starting the actual treatment. One drug marks cancer cells with eGFP, which is visible under a microscope. This allows Ambrego Labs to test that exactly all of the cells in the patient's cancerous cells sample are targeted and none of the healthy cells are, as a quality control before sending the other drugs to the oncologist. The oncologist will then use a different version of the drug that makes cancer cells visible on MRI to check that the correct cells are being targeted via 3D MRI.

The treatment design also reduces the stress on the patient. By stopping the cell cycle of the cancer cells, cell growth is stopped and the cancer cells can be destroyed in a gentle way.

Because of these two things, a far better side effect profile than with chemotherapy is to be expected.

Why are you going the path of n-of-1 trials instead of traditional trials that lead to approval of the treatment for general use?

The drugs are calculated and produced on a per patient basis. Still, because of the toolbox-like nature of the Ambrego drugs, we believe that they have a consistent efficacy and safety profile in patients, but we have yet to prove this.

This will be done in the first human n-of-1 trials. With these results, we can discuss with authorities on the best path to standarization.

Why can't you treat cats in the EU? My cat is sick now and I need help urgently!

The EU Directive 2010/63/EU of September 22, 2010 on the protection of animals used for scientific purposes requires mice, rats, guinea pigs, golden hamsters, Chinese hamsters, Mongolian gerbils, rabbits, dogs, cats, non-human primates, frogs and zebra fish to be purpose-bred if they shall be used for experimental animal treatments.

Thus, the Ambrego treatment must first be approved for use in animals in the EU, which, while we are working towards this, does take a long time due to the individualized nature of the Ambrego drugs.