SWITZERLAND, SATURDAY, 7 MARCH 2020 5:15 PM CET

Demiurge is responding to the global outbreak of the 2019 novel coronavirus (COVID-19) through the appropriate use of our AI platform that can make accurate drug discoveries for diseases with limited available clinical data.

Based on the deep analyses of published studies, clinical data and case reports on COVID-19 and our previously announced four AI-based discoveries for COVID-19, we hereby officially announce the 5th AI-based discovery of the complete aetiology of COVID-19 as below:

Viral survival strategy: COVID-19 adopts a unique unbiased survival strategy of balancing viral replication with viral spread, in stark contrast to other viruses that typically trade off one against the other. For example, MERS coronavirus adopts a survival strategy that prioritizes viral replication over viral spread, whereas influenza viruses adopt a survival strategy that prioritizes viral spread over viral replication.

Viral infection stages: COVID-19’s course of infection bifurcates between (i) a self-limiting stage for mildly-to-moderately symptomatic patients when the unbiased survival strategy of COVID-19 is disadvantageous against the host immunity, and (ii) a self-amplifying stage for severely-to-critically ill patients when the unbiased survival strategy of COVID-19 is advantageous over the host immunity.

Viral entry: COVID-19 directly enhances its affinity with the functional host-cell receptor angiotensin-converting enzyme 2 (ACE2) and thus targets only stem-like cell types whose ACE2-dependent baseline activities regulate a myriad of homeostatic cellular processes that maintain genome, proteome, ion, energy, and immune system stability in a tissue-specific fashion.

Viral replication and egress: COVID-19 indirectly enhances the activation of the distal promoters of the ACE2 gene in the host cells, resulting in (i) the suppression of ACE2 expression in the host cells, (ii) the hijack of the intracellular machineries of the host cells to enable viral replication and egress, and (iii) the disruption of the homeostatic functions of the host cells.

Viral microenvironment: COVID-19 leverages the disrupted homeostatic functions of the host cells to create a favorable microenvironment that (i) activates the innate immune response to further reduce ACE2 expression to boost viral replication and egress, and (ii) suppresses the adaptive immune response to further reduce host cell death to sustain viral replication and egress.

Viral adaptive mutation: COVID-19 leverages the favorable microenvironment to further enhance its inherently strong adaptive mutability as an RNA virus, thus developing robust resistance to effective but non-curative treatments that predominantly inhibit either viral replication or viral spread and making it unlikely to develop effective vaccines.

Viral latent Infection: COVID-19 can flexibly switch to the latent infection mode under the pressure of strong host immunity and/or during effective but non-curative treatments. COVID-19 can also switch back to the productive infection mode when the host immunity is weakened and/or the effective but non-curative treatments are ended, resulting in inevitable rebound and frequent reinfection among asymptomatic COVID-19 carriers.

Viral latent adversity: When effective but non-curative treatments switch COVID-19 to the asymptomatic latent infection mode, COVID-19 can still chronically disrupt systemic genome, proteome, ion, energy, and immune system homeostases by affecting the baseline activities of ACE2-expressing host cells in multiple organs over years. When the cumulative disruption of multi-level homeostases is sufficient to switch COVID-19 back to the symptomatic productive infection mode, COVID-19 can initiate an accelerate disease progression and trigger severe cytokine storms and fatal comorbidities.

Therefore, COVID-19 is an unprecedented coronavirus that causes both acute respiratory illnesses for symptomatic patients and chronic systemic disorders for asymptomatic carriers.

Effective but non-curative treatments or vaccines may induce a latent preservation of COVID-19 in patients instead of a complete eradication, and the adversity of latent COVID-19 will inevitably trigger a viral rebound, an accelerated progression, and an increased mortality rate.

In light of the foregoing complete aetiology of COVID-19, we hereby recommend the following optimal control & treatment strategy for COVID-19:

• Quarantine but no treatment for asymptomatic carriers and mildly symptomatic patients to leverage the host immunity’s advantage over COVID-19 at the self-limiting stage, resulting in COVID-19 eradication.
• Unbiased curative treatment (e.g. PI3K inhibitors) for moderately-to-severely symptomatic patients to eliminate COVID-19’s advantage over the host immunity at the self-amplifying stage, resulting in COVID-19 eradication.
• Unbiased specialized treatment (e.g. irinotecan + etoposide) for critically ill patients to reduce mortality.

In pandemic settings, public interest in treatment availability and commercial interest in marketing exclusivity are usually misaligned, but we have no doubt that public interest must be prioritized because lives matter above all else.

We have thus chosen to announce those discoveries to the public first without any delay in either applying for patent protection in secret or working with biopharmaceutical companies in private, so as to waive commercial interests once for all to speed up cross-border concerted efforts to solve the unprecedented global crisis posed by COVID-19.

About Demiurge Technologies AG

Demiurge Technologies is a research-based AI-biopharmaceutical company that transforms publicly available life science data into precise disease models in areas with unmet medical needs. The company pioneers a self-correcting scientific approach that validates disease models with the accuracy of AI-based predictions of phase 3 clinical trial outcomes. The company also pioneers a self-sustaining business that commercializes disease models by accelerating the AI-based discovery and development of innovative medicines. Demiurge started in 2016 with headquarters in Switzerland.

AI has been an emerging powerful approach to deeper disease understanding and faster drug discovery, yet it must be put to the most rigorous test to prove its worth under public scrutiny. Demiurge has predicted the outcomes of more than 90 phase 3 clinical trials across multiple therapeutic areas and achieved more than 80% accuracy. Furthermore, we have been inviting the public to witness our future predictions of clinical trial outcomes on Twitter (@DemiurgeTech).

Therefore, we officially put forward AI-based discoveries of the complete aetiology of COVID-19 and the candidate treatments for COVID-19 as scientific hypotheses only and invite the world to validate their potential to solve the unprecedented global crisis posed by COVID-19.

Disclaimers

This material is intended for information purposes only and is provided without any warranty of any kind, either expressed or implied. These statements are not guarantees of future performance, condition or results. Figures and graphs in this presentation are for illustration only and are may not match the actual scale. This presentation contains certain forward-looking statements. These forward-looking statements may be identified by words such as ‘believes’, ‘expects’, ‘anticipates’, ‘projects’, ‘intends’, ‘should’,‘seeks’, ‘estimates’, ‘future’ or similar expressions or by discussion of, among other things, strategy, goals, plans or intentions. Various factors may cause actual results to differ materially in the future from those reflected in forward-looking statements contained in this presentation, among others: 1 pricing and product initiatives of competitors; 2 legislative and regulatory developments and economic conditions; 3 delay or inability in obtaining regulatory approvals or bringing products to market; 4 fluctuations in currency exchange rates and general financial market conditions; 5 uncertainties in the discovery, development or marketing of new products or new uses of existing products, including without limitation negative results of clinical trials or research projects, unexpected side-effects of pipeline or marketed products; 6 increased government pricing pressures; 7 interruptions in production; 8 loss of or inability to obtain adequate protection for intellectual property rights; 9 litigation; 10 loss of key executives or other employees. Demiurge Technologies AG (“Demiurge”) undertakes no duty or obligation to publicly update or revise the forward-looking statements or other information contained in this presentation. You should not view information related to the past performance of Demiurge and its affiliates or information about the market, as indicative of future results, the achievement of which cannot be assured. While some information used in this document may have been obtained from various published and unpublished sources considered to be reliable, Demiurge neither guarantees its accuracy or completeness nor accepts liability for any direct or consequential losses arising from its use. Amounts and percentages may reflect rounding adjustments and consequently totals may not appear to sum. None of the information in this presentation does, by itself, constitute an offering or an offering circular according to Article 652a of the Swiss Code of Obligations and is subject to change without notice. Any offer or solicitation with respect to any securities that may be issued by Demiurge will be made only by means of definitive offering memoranda or prospectus, which will be provided to prospective investors and will contain material information that is not set forth herein, including risk factors relating to any such investment. Before making an investment, you must obtain and carefully read all information needed to evaluate the investment, including, but not limited to the documents providing important disclosures regarding risks, fees and expenses. An investment in Demiurge may be volatile and can suffer from adverse or unexpected market moves or other adverse events. Investors may suffer the loss of their entire investment. An investment in Demiurge will be discrete from an investment in any funds or other investment programs managed by Demiurge and the results or performance of such other investment programs is not indicative of the results or performance that will be achieved by Demiurge or such investment programs.

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