The promise of personalized medicine came into focus with the sequencing of the human genome. However, it is only now with technological advances on several fronts that the field of personalized medicine is coming into its own.

A number of approaches have recently been adopted in the cancer field. These approaches all have strengths and drawbacks.

Most familiar are tests that focus on 1-2 genes to determine suitability for a particular therapy, such as Her2 for Herceptin or KRAS for an EGFR inhibitor. On the plus side, these tests are highly validated; the downsides are that there are still relatively few of them, and if the drug is not indicated there is little insight.

Testing via a gene panel is also not unusual. There are two types of approaches here: an aggregation of tests such as above. This allows examination of multiple ideas simultaneously, and so can provide more insight than a single test alone if the “usual suspects” are not indicated. However, there is less likely to be validation of the use of certain targets in cancers other than the specified indication, making a medical decision much more challenging.

The other type of gene panel is prognostic testing, such as OncotypeDX for breast cancer. These approaches are quite familiar and form a useful tool an early stage in determining the appropriate level of aggressiveness, but at a late stage they cannot provide therapeutic guidance.

Chemosensitivity/in vitro screening is yet another approach that is sometimes taken. Tumor cells are grown in a petri dish and 10-20 different chemotherapeutics are tested to see which cause the cells to die. Because cells grown in a petri dish lack the stroma and other supportive structures present in vivo, the value of these approaches, the results are not robust: studies have shown that such assays are fairly good indicators of which therapies won’t work, but successfully killing cells in vitro has little indication of whether it will work in the patient (REF). An additional downside is that this method is only applicable to traditional chemotherapeutics (not targeted therapies) and it requires a substantial amount fresh tissue, so if not planned for in advance a new biopsy will typically have to be done.

Xenograft models are also occasionally used. Tumor cells are implanted into immune-deficient mice, and allowed to grow. Then a drug of choice is given to the mice, to determine whether the cancer responds. A mouse model will likely have higher fidelity than an in vitro model; however, it is quite expensive, and pragmatically can only be used to choose within a few drugs. (It could potentially be considered as a validation experiment for CollabRx ONE). Additionally, like chemosensitivity, it will likely require a fresh biopsy to gain the requisite tissue.

CollabRx ONE is a unique and novel approach. It is most similar to the gene panels described above, except that we are looking not just at a handful of genes but the entire genome, and can identify options among the majority of the pharmacopeia (2000+ FDA approved drugs) and investigational drugs. We do our investigation at the functional/pathway level – so rather than relying on a single data point to formulate hypotheses, we look for 20-30 data points that all point in the same direction, and identify mechanisms that appear to be driving the cancer and drugs that are known to impact those mechanisms. Beyond the specific analysis, we will partner with you to design/conduct studies to validate results and answer ongoing questions that may inform treatment decisions.

There are two key downsides to this approach: it’s novel approach, meaning there is very little data to prove its utility, and it is not reimbursed by insurance carriers. (We are now collaborating with several top medical centers to design studies to provide supporting data.) We don’t accept patients whose oncologists are not on board with the value of this approach, so we’ll want to have a brief (15-20 mins) phone call with you to discuss the approach, confirm that the prognosis is sufficient for us to be of help. When the results are available, we will plan to meet with you, and usually the patient/family as well, to discuss them (typically 1 hr). We are committed to not coming between doctor and patient, so, for example, we don’t release results to the patient without you.

• CollabRx ONE has a dedicated research team that works on behalf of you and your patient to identify potential treatment choices.
• Our program considers options from among thousands of possible therapeutic options, including those drawn from clinical trials, based on their unique cancer profile. We look at thousands of genes and are continually evaluating new technologies that can yield useful data—leaving no stone unturned.
• We will not interfere with the physician/patient relationship – we will ensure you are involved at every step, including presenting of results.
• Our involvement does not end with the results of our analysis; we will partner with you to generate and interpret additional molecular information that may be useful in guiding decision making and incorporate new data points – e.g., response to a given therapy – into our thinking about the disease.
• We are straightforward with you and your patients about the possibilities for success of this program, based on our experience.

Our best predictive value is around drugs or biologics whose mechanism is not simply cytotoxicity – e.g., targeted agents (for cancer or other diseases) rather than traditional chemotherapeutics.

The analysis will be measuring the state of the tumor at the time of biopsy. If the cancer has likely mutated since then (e.g., if there was a durable response on a therapy and a recurrence) the results will likely be inaccurate. In cases such as this, a new biopsy may be advisable.

Metastases may have different characteristics than the primary tumor, and it is possible that they have different characteristics from each other. We aim to get samples from the most clinically dangerous metastases.

Within a metastasis, the tumor may be heterogeneous. We get replicates from different loci of the tumor where possible to sample the heterogeneity.

Our methodologies have strong precedent in the pharmaceutical industry, but its application to individual patients is new and validation of its utility is still underway.

Most importantly, there is much that is unknown about the pathways that we are investigating, which could cause our findings to be incomplete and therefore not efficacious. Rest assured that we continuously seek out the best information to ensure that we have the highest chance of success.

The approach is applicable to all types of cancer.

Many of our patients have already failed standard of care approaches. For those who have not, we would not recommend going against the standard of care – the results should properly be used as a “plan B” in case of failure, and validation studies can be performed to further establish the results.

The process takes a minimum of 3 weeks, but can take longer if there are logistical complications.

At minimum, an upfront 15 to 20 minute conversation to determine whether there is a mutual fit and a 1-hour meeting to review the results are needed. However, we are happy to engage at any or all points through the process as appropriate.

As soon as you and your patient are ready to move forward, we will arrange for biopsies, usually from already collected tumor samples or previous biopsies, to be sent to CLIA-approved laboratories that run CollabRx ONE specified tests.
• Our experts will then perform extensive genomic research and in-depth analysis of the molecular profile, in order to suggest therapy options that could address the mechanisms responsible for sustaining your patient’s illness.
• We will then present the results, and the scientific rationale, to you and your patient. Our goal is to provide information and context/further studies to help you adjust your patient’s treatment plan with the findings from the personalized research as appropriate.

You will get a report containing the details of the mechanisms that we have found, drugs that address those mechanisms, and recommendations for validation studies that may further support the findings. We will be available to support implementation of these (or other) validation studies and perform additional analyses as new options or questions arise. We will also provide the raw data upon request.