COVID Moonshot: PostEra’s machine learning platform in real world drug discovery

In March 2020 PostEra helped launch COVID Moonshot, which became the world’s largest open-science initiative to develop a COVID antiviral cure.

With low and middle income economies limited in access to vaccines, Moonshot set out to develop patent-free compounds that would be readily accessible for all patients around the world.

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PostEra’s machine learning drove the prioritization of crowdsourced ideas

Moonshot crowdsourced antiviral ideas, inspired by a fragment screen, from over 400 scientists around the world. PostEra’s machine learning drove the prioritization of these ideas and designed the synthesis of all 2000 compounds made as part of COVID Moonshot as well as using our ML technology to develop new chemotypes.

In 18 months, the project progressed from a fragment screen to the nomination of Development Candidates ready for IND-enabling studies.

Property	Target Range	Cold Start Mar 2020 --> Dec 2021
Protease Assay	IC50 < 50 nM	40nM
Viral Replication	EC50 < 0.2µM	0.15 μM in A549 CPE
PK-PD	Cmin > EC90 (plaque reduction) for 24h	Current projected human dose ~220mg QD ; 100mg BID
Coronavirus spectrum	SARS-CoV2 B1.1.7 , 501.V2, B.1.1.248 variants essential SARS-CoV-1 & MERS desirable	Active against B1.1.7 , 501.V2 in cellular assays
Route of administration	oral	BO = 45% in rat
Solubility	> 5 mg/mL, >100µM tolerable	750 µM
Half-Life	Ideally >= 8 h (human) est from rat and dog	Rat 2h, human predicted PK sufficient
Safety	No significant protease activity >50% at 10μM (Nanosyn 61 protease panel) Only reversible and monitorable toxicities (NOAEL > 30x Cmax) No significant DDI – clean in 5 CYP450 isoforms Critical transporter check (e.g. OATP) hERG and NaV1.5 IC50 > 50 µM No significant change in QTc No mutagenicity or teratogenicity risk	Protease panel clean on analogues Eurofins / CEREP 44 target panel clean Cyp450: clean except 2A4 (3uM) No hERG activity Live phase planned Lead compounds are clean in AMES +/- S9

What's Next?

$11M

Moonshot attracted an $11M grant to move our patent-free compounds through IND-enabling studies and into clinical trials.

$68M

PostEra and members of the Moonshot consortium successfully secured a $68M grant from the NIH to develop antivirals against other viruses of pandemic concern.