Proprietary and confidential — do not distribute

AUGUST 2020

H01 for COVID-19Stanford Proposal

COVID-19 continues to disrupt and destroy

communities

At best, vaccines are likely to reach only

20-30% of the world by end of 2021

We need an inexpensive, oral medicine to

manage COVID-19 lung disease and death

worldwide (both higher and lower income countries)

PROBLEM: COVID-19 urgently needs accessible & effective drugs

Multiple Vaccines Under Development – Most Early Stage

A repurposed medicine with an established

safety and tolerability profile

New Stanford research suggests

high potential for efficacy in COVID-19

Available as an oral tablet that costs

Prof Paul BollykyMD, PhD

Stanford; HA KOL

Dr Nadine NagyPhD

Stanford; 10 years covering HA

Dr Andy WardleMD, MBA

Biotech, VCBCG

CORE TEAM

ADVISORS

Stanford team of hyaluronan experts

Experience in repurposing & development

Prof Kevin GrimesMD, PhD

Co-Director Stanford SPARK

Meg SnowdenJD

25 years biotech legal veteran

Dirk MendelPhD

25 yrs preclinicaldevelopment , 4 NDAs

Egan PeltanPhD

Discovery/Development

Who are we?

PARTNERS

Alex TancrediMBA

Biotech, BCG, Private Equity.

Anissa KalinowskiMBA, MSc

Genentech, Roche

Mridula ShuklaMS, Ignite

Biotech, Regeneron, Thermo Fisher

Dr Joelle RosserMD

Internal Medicine, Stanford Fellow

Prof Lawrence SteinmanMD PhD

Multiplemulti-billion-dollar drug discoveries

Business Dev. Regulatory Clinical Dev.Principal Invest. Principal Scientist Operations Pre-Clinical

Background

The INHALE Study

Opportunities to Support

Agenda

Presentation: - Fever, cough, shortness of breath

Hospitalisation: - Fluid in the lungs prevents gas diffusion- 10% hospitalised patients require intubation

Mortality:- Survival rate of intubated patients is ~50%

If we reduce COVID19 lung secretions and prevent intubation we will save lives

COVID-19 patients “drown” in their own lung secretions

Hyaluronan

Background: - Hyaluronan is a highly viscous polymer

that traps 1000x its mass in water- Cells produce hyaluronan when infected with virus

Approach: To test this in COVID-19 we infected human lung cells with COVID-19 and measured hyaluronan

We also collected sputum samples from COVID-19 infected patients at Stanford University

Hypothesis: Hyaluronan drives deadly features of COVID-19

COVID promotes hyaluronan production by lung cells in culture

COVID19 leads to up to 25x increase in hyaluronan in the sputum

Hyaluronan

Finding: Hyaluronan is greatly increased in COVID-19 infection

COVID patient lungs

Brown staining represents hyaluronan filling airspace, retaining water, and obstructing gas exchange

Finding: Hyaluronan is blocking COVID patient airways

Healthy patient lungs

25x1000x

_____________________________________________________________________________

25,000x

Hyaluronanvs healthy

water due to hyaluronan

water trapped

Finding: Hyaluronan traps fluid in COVID-19 patient lungs

Hyaluronan traps 1000 times its weight in water. In COVID lungs, hyaluronan is 25 times higher than healthy lungs

Causes airway blockages

Patients ‘drown’ from their own lung secretions

1

2

Conclusion: Hyaluronan is a major driver of COVID-19 disease

Proprietary and confidential — do not distribute

How can we inhibit sputum hyaluronan production?

• Repurposed drug currently used to prevent gallstones

• Available in most of the world

• Oral tablet

• Long shelf life and no special storage requirements

• More than 50 years of approved use in Europe

• Excellent safety profile

• Cost effective therapy (

Our agent reduces hyaluronan in saliva and lung secretions

NEW DATA: Human proof of concept in process/to be published

70% decrease in hyaluronan seen in human study

Potential to manage COVID-19 disease by using our agent

Background

The INHALE Study

Opportunities to Support

Agenda

- Investigator initiated, international, multi-center, randomised controlled study

- Proof of concept: reduction in lung morbidity and mortality

- Sites and investigators appointed (SPARK network)

- FDA regulatory approvals underway

The INHALE Study

Stanford group now leading a new COVID-19 study

Enrolment

Agent

Follow Up

Screen (48hr) Treatment Period3 weeks or until discharge

PBO

Readout

2:1

Follow Up (2 wks)

R

3-week study to assess treatment benefit with Agent

Improve blood oxygenation, reduce ICU admissions and intubationsPotential use both in and out of hospital

July Aug Sep Oct Nov Dec Jan 2021+

INHALE

FDA IND

Clinical

Regulatory

Final Protocol and SAP

EMA CTA

Operations Core Documents

Follow-on Development Follow-on Study*

Finance & Ops

IRB, Lageso, REC

FDA

Projected Timelines

Manufacturing Develop Global Supply Chain Strategy

*Larger scale studies in additional markets can be expedited pending funding.

Anti-Virals

Reduce/prevent viral shedding- Remdesivir- Favipiravir

Reduce immune system activity- Dexamethazone- Anakinra- Tocilizumab

Direct targeting of lung secretions, scarring, and fluid

build up

Our Agent Immune Modulators

Our Proposal: Unique mechanism with outpatient potential

Hospitalised patients and advanced care settings

Both In & out of hospital patientsBoth developed & developing healthcare systems

Hospitalised patients and advanced care settings

Planning for large scale outpatient clinical trial

The plan is to follow The INHALE study with an outpatient trial in a low-income setting

Early stage planning/talks initiated

Trial of ~700 patients, placebo controlled study could detect hard clinical outcomes (hospitalisation, mortality)

Unique mechanism means our Agent arm can be added to an existing trail or new adaptive trial

Background

The INHALE Study

Opportunities to Support

Agenda

We need your financial help to make this possible

Pre-clinical work complete Human dose finding complete Protocol developed 3 clinical sites ready to startStudy IND developed CMC completeDrug supply in hand Study procedures in place

Resources Needed

~$1.5 million to complete trial

US Patient Costs $360KEU Patient Costs $370KDrug Costs $130KStudy Management $400KData Analysis $50KLogistics $140K

Assets in Hand

There are multiple ways to support a COVID-19 solution

Develop Global SupplyCOVAX-like model for manufacturers

$TBD

Establish Proof of ConceptFund The INHALE Trial $1.5 million

Establish Clinical EfficacyFund Low-Income Country Clinical Trial ~$4 million

Opportunity to overcome the largest health crisis of our lifetime

Thank you

US Case StudyPopulation: 330MImpact of Agent: 20% reduction in mod-severe infections

Avoid:1.5M hospitalisations500k ITU admissions250k respiratory associateddeaths

Worldwide impact would be many multiples of this

Slide Number 1Slide Number 2Slide Number 3Slide Number 4Slide Number 5Slide Number 6Slide Number 7Slide Number 8Slide Number 9Slide Number 10Slide Number 11Slide Number 12We have an approved drug that inhibits hyaluronan synthesisOur agent reduces hyaluronan in saliva and lung secretions �Slide Number 15Slide Number 16Slide Number 17Slide Number 18Slide Number 19Slide Number 20Slide Number 21We need your financial help to make this possibleThere are multiple ways to support a COVID-19 solutionThank you