Report to period ending 31 December 2016
The DiaTech MiCK Information Memorandum was released in November 2015, with first funding taking place in January 2016. Since then, although the level of funding has been disappointing, with parent company support and the support of certain shareholders of the parent company, the Company has been able to continue its research and development at a reasonable rate.
In the original embodiment of the MiCK assay, the platform used proprietary technologies that measured optical density (OD) to track cellular morphological changes, in particular membrane blebbing, as a specific indicator of apoptosis. Real-time optical density monitoring permitted an integrated analysis of specific, single-cell responses over a pre-determined culture period. The continuous measurement modalities provided an automated, continuous read of in vitro apoptosis, that directly quantified drug-induced cell death in real-time. This data delivered a prediction of tumor response probability, or resistance, to specific cytotoxic agents. During the year it was found that the OD measurement, which formed the basis of the MiCK assay, was not performing with the reliability and reproducibility which is required of a diagnostic product and was associated with a coefficient of variability (CV) of 20 to 30 percent. For approval through the FDA, a CV of about 8-12 percent is expected.
It was recognized that the historic MiCK assay was a correlated measure of apoptosis and that many factors can adversely affect OD response curves such as (but not limited to) cell proliferation, cell plating density, uniformity of cell monolayer, drug optical properties and necrosis. Additionally, the use of Vmax to quantify and classify drug sensitivity has several inherent issues which can lead to miss-classification of cytotoxic drug apoptotic response. Additionally, since inception of the MiCK platform there have been major advances in instrumentation design and molecular probes which now make it possible for a MiCK platform transformation utilize more sensitive, specific and direct measures of apoptosis.
DiaTech has taken advantage of these technology advances to optimize the MiCK assay performance. The most significant update was transitioning from a single parameter optical density spectrophotometer instrument platform to a multi-parameter, multi-modal optical density, fluorescence, luminescence and cell image based instrument platform. This transition allowed DiaTech to explore use of fluorescent and luminescent molecular probes and markers to directly quantify and image simultaneously the various apoptotic pathway events allowing for continuous, real-time, monitoring of tumor cell response to cytotoxic drug exposure.
Development efforts have focused on 20 or more potential molecular probes and markers which are specific to four distinct apoptotic processes and features: caspase activity, mitochondrial membrane potential, DNA fragmentation, and loss of cytoplasmic membrane integrity. These efforts have led to a configuration allowing simultaneous real-time whole well monitoring, in addition to cell imaging of DNA fragmentation, caspase activity, mitochondrial membrane potential, cell viability and cell morphology. The Company eventually found 4 compatible molecular probes and combining these has now produced a CV of <5% which is regarded as outstanding. Using the Company’s assay set, the medical profession is now genuinely able to look forward to a time when personalized treatments for cancer can be regarded as a reality.
One consequence of the MiCK assay optimization is that the Company’s previous clinical trial results will have to be revalidated using the updated assay. Because the assay is no longer solely based on OD, the former MiCK technology has been renamed ChemoINTEL.
During Q1-3 of 2017, the Company intends to continue to optimize the assay. During Q4 of 2017 and Qs 1-3 of 2018, the Company will conduct a Training Study and complete Analytical Validation. The initial work will be done with breast and ovarian cancers. At the end of this period, the Company expects to have a substantial value inflection, based on the demonstration of the assay’s predictive capabilities, which may or may not lead to a Liquidation Event at that time.
In the event there is no Liquidation Event in Q4 of 2018, Clinical Validation studies will be conducted in breast and ovarian cancers. These studies will take place over Q1-Q3 2019. At the end of these studies, the Company will market an LDT and expects a strong inflection point, which they hope will lead to a Liquidity Event.
If there has been no Liquidity Event at the end of the Clinical Validation Studies, the Company will further develop the assay by conducting Clinical Utility Studies. These will also be performed on breast and ovarian cancers and are expected to last 18 months over 2020 and Q1 and Q2 2021. FDA approval should follow 6 to 9 months later. A Liquidity Event could happen at any time after the end of the Clinical Utility Studies phase and some trading income from collaboration agreements could be expected at that time.
The work that has been done over 2016 has resulted in a better and more reliable assay than was the case when the IM was published in November 2015. This has been at the expense of a more limited group of cancers under test. Management is confident that this change of emphasis will lead to a technologically improved product and to an earlier Liquidity Event than may have occurred under the original program, albeit at the expense of a narrower series of cancers which have been tested. The cost to arrive at this result is expected to be significantly lower than was the projected in the Information Memorandum.
In the event that the level of funding is improved and there are surplus funds after engaging in the basic program outlined above, Management intends first to reduce the time to complete the development program and then to add additional cancer types to the clinical development program. Management believes that with a rate of funding significantly above the minimum comfortably required to complete the above program, the time to completion can be reduced by 6 to 9 months, with proportionate time savings over the total time period of the studies to be completed.
In summary, it remains the belief of Management that the Company has potentially world class technology which will take 2 years to its first value inflection point and 4 years to its final inflection point, at a reduced cost as compared with the development program as originally envisaged in the Information Memorandum and with a technologically improved assay, which will enable true personalized medicine for the first time in the field of chemotherapy.