Cloudbreak - Cidara Therapeutics€¦ · whether Cloudbreak candidates, including CB -012, will achieve the major attributes believed to be needed in flu such as broad spectrum, superior

© Cidara Therapeutics 2019

CloudbreakCloudbreak Antiviral Conjugates (AVCs)July 2019


Forward-Looking Statements

These slides and the accompanying oral presentation contain forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Such statements include, but are not limited to, statements regarding the effectiveness, safety, long-acting nature, anticipated human dosing, anticipated trial design and timing, the potential to treat and/or prevent infections, the degree to which results in our Phase II clinical trials predict results in our Phase III clinical trials, and other attributes of rezafungin; as well as the potential market size for rezafungin, ability of rezafungin to capture market share from existing therapies, and the advantages of rezafungin in other settings of care.

Certain statements regarding our Cloudbreak platform are also forward-looking including statements regarding whether our Cloudbreak platform can identify product candidates with intrinsic antimicrobial activity and immune engagement that will increase efficacy or represent an improvement over existing anti-infective agents; whether Cloudbreak candidates, including CB-012, will achieve the major attributes believed to be needed in flu such as broad spectrum, superior resistance profile, protection for high-risk populations, expanded efficacy window, long duration of action and rapid onset of activity, or flexible administration; whether results observed with Cloudreak influenza candidates, including CB-012, in-vitro or in animal studies, including, potency and broad coverage, activity against resistant strains, activity in immune compromised patients, extending the treatment window, extended half-life and long duration of action, improved viral clearance in the lungs, improved reduction in inflammatory cytokines, and a robust safety profile or other observed attributes represent an improvement over existing therapies or will also be observed in human use; and whether our Cloudbreak platform can be expanded to identify product candidates to treat or prevent other viral diseases, such as RSV, HIV, Dengue or Zika. This presentation also contains estimates and other statistical data made by independent parties and by Cidara relating to market size and growth and other data about Cidara's industryThese data involve a number of assumptions and limitations, and you are cautioned not to give undue weight to such

estimates. Projections, assumptions and estimates of the future performance of the markets in which Cidara operates are necessarily subject to a high degree of uncertainty and risk. Risks that contribute to the uncertain nature of the forward-looking statements include: Cidara’s abilityto obtain additional financing; the success and timing of Cidara’s preclinical studies, clinical trials and other research and development activities; receipt of necessary regulatory approvals for development and commercialization, as well as changes to applicable regulatory laws in the United States and foreign countries; changes in Cidara’s plans to develop and commercialize its product candidates; Cidara’s ability to obtain and maintain intellectual property protection for its product candidates; and the loss of key scientific or management personnel. These and other risks and uncertainties are described more fully in Cidara’s Form 10-K as most recently filed with the United States Securities and Exchange Commission (SEC), under the heading “Risk Factors.” All forward-looking statements contained in this presentation speak only as of the date on which they were made. Cidara undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made.


Prevention and treatment of influenza today have limitations

In 2018, 650,000 people died due to influenza.

PreventionFlu vaccine effectiveness averages 40%, and often as low as 10-25% in the elderly, very young, and immuno-compromised. Flu vaccine manufacturing is difficult to predict and scale. The net result: hundreds of millions of people are unprotected.

TreatmentTreatments today are limited to two classes, with the latest already exhibiting >10% resistance. Treatments are generally ineffective if started beyond a 48 hour window and in complicated hospitalized patients.


Cloudbreak platform – multimodal mechanism of action: intrinsic antimicrobial activity & immune engagement

One molecule, multiple mechanisms

Cloudbreak candidates targeting viral infections are called Anti-Viral Fc-Conjugates (AVCs), single molecules comprising two distinct moieties with discrete, yet complementary mechanisms of action: the Targeting Moiety (TM) and Effector Moiety (EM).

AVCs not only mediate pathogen clearance through a multimodal mechanism of action but also have potential for months of activity with a single dose.

VIRUS

Potent small molecule inhibitor binds a conserved essential target

Fc recruits immune system

Effector Moiety (EM)Fragment crystallizable (Fc) region of human IgG1 antibodies, which was selected to maximize engagement of the human immune system via Fc-gamma (Fcγ) receptors, and for its long half-life.

Targeting Moiety (TM)Novel, highly potent small molecule that binds surface targets on the pathogen to directly destroy it and/or inhibit replication.

Our Cloudbreak candidates are designed to counter infection in two ways:1) by directly targeting and destroying invading pathogens, and2) by focusing the immune system at the site of infection.


Our AVC uniquely achieves the major attributes needed in ’flu

Broad spectrum, universal coverage

Superior resistance profile

Protection for High-Risk Populations

Expanded efficacy window

Long duration of action

Rapid onset of activity

Activity against pandemic and seasonal influenza A and B viruses not covered by existing vaccines and treatments.

Expected lower viral resistance due to the AVC multimodal mechanism of action.

Unlike vaccines, AVCs work in immune compromised hosts due to their potent, intrinsic antiviral activity.

AVCs demonstrate the potential of expanding the efficacy window beyond the current 48 hours of existing treatments.

AVCs are designed to provide protection for a full flu season with a single subcutaneous dose.

Immediate effective protection and treatment, unlike vaccines which require 14-days to elicit an immune response.

Flexible administration Equivalent effective exposure via subcutaneous, intravenous or intramuscular administration.








Flexible administration

Our AVC covers both pandemic and seasonal ’flu strains

A/Texas/36/91 H1N1

100%

0%0 14Days

Surv

ival

CB-012 0.4 mg/kg

Neg control (Fc only)

Dose

14Days

100%

0%

0

Surv

ival

A/Hong Kong/68 H3N2

CB-012 0.4 mg/kg

14Days

100%

0%0

Surv

ival

B/Malaysia/04

CB-012 0.4 mg/kgA single, low dose of CB-012 protected mice against the three lethal infection models shown here.


Our AVC retains activity against drug resistant strains

14Days

100%

0%

0

Surv

ival

Neg control (Fc only)Tamiflu 20mg/kg10 doses

Dose

CB-012 in Tamiflu-resistant H1N1

DosesCB-012, 2mg/kg1 dose

A/Perth/261/2009, Strain H275Y









Our AVC retains activity in immune-compromised hosts

*Severe Combined ImmunoDeficiency

Immune competent mice Immunodeficient mice

0%

Vehicle

0.3 mg/kg

0 14Days

Surv

ival

100%CB-012

0%

Vehicle

0.3 mg/kg

0 14Days

Surv

ival

100%CB-012 DoseDose

CB-012 protects immune competent BALB/c mice in a lethal influenza model (H1N1: A/Puerto Rico/8/34).

CB-012 also protects immune deficient BALB/c SCID* mice in the same lethal influenza model.









Our AVC extends the window of time for treating ’flu

A single low dose is effective when administered 72 hours after infection

0 72 9624HOURS

48

CB-012

Tamiflu

INFECTION

CB-012:Tamiflu:

10 mg/kg20 mg/kg

Dose

Doses

Fc only

Mouse lethal endpoint model H1N1









Extended half-life translates to long duration of prevention

CB-012 1.25 mg/kg

-28 0 14-14

100%

0%

Surv

ival

DAYS

Dose Infection

CB-012

Control

Lethal influenza model (H1N1: TX/36/91 in mice)

A single low dose remains effective when administered a month prior to infection









Cmax 1 hrC

once

ntra

tion

Lung

Plasma

AVCs achieve effective exposure within an hour of administration

CB-012 protects within 60 minutes of administration.

In contrast, vaccines take about six months to manufacture, and protection begins ~14 days after administration.









AVCs achieve effective exposure through multiple routes

CB-012 dosed by different routes achieves consistently high concentrations

SubqIMIV








Mouse PK by dosing route


Dose-dependent viral clearance in lungs

Why this is important: Severe influenza infections are caused by the virus moving from an initial upper respiratory tract infection to the lungs. Recent studies in lethal mouse H1N1 infection models demonstrate that single, low doses of CB-012 rapidly lower viral burden orders of magnitude better than Tamiflu (Oseltamivir).

12

PBS control

Fc control (3 mg/kg)

Oseltamivir (5 mg/kg, BID x 4)

CB-012 (0.1 mg/kg)

CB-012 (0.3 mg/kg)

CB-012 (1.0 mg/kg)

CB-012 (3.0 mg/kg)

PFU / g (Log10)103 104 105 106 107 108

Viral burden (H1N1) – Day 4 post-infection


Dose-dependent reduction in inflammatory cytokines in lungs

Why this is important: Morbidity and mortality from severe influenza is ultimately caused by virally induced influx of pro-inflammatory cytokines in the lungs. One potential concern of using an immunotherapy such as Cloudbreak to treat influenza is whether the Fc fragment would exacerbate cytokine induced inflammation. The results of the H1N1 lethal infection model show just the opposite: a CB-012 dose dependent decrease in pro-inflammatory cytokines TNFα and IL-6 in infected lung tissues.

13

Concentration (pg/mL)

0 400 800

PBS control

Fc control (3 mg/kg)

Oseltamivir (5 mg/kg, BID x 4)

CB-012 (0.1 mg/kg)

CB-012 (1.0 mg/kg)

CB-012 (3.0 mg/kg)

Uninfected

TNFα (Lung)

Concentration (pg/mL)

IL-6 (Lung)

0 1000 1500


Our AVC demonstrates robust safety in rats and primates

CB-012 has broad safety marginsThe data show the results of a 14-day safety study in which rats and primates were dosed by IV infusion twice: on days zero and seven. Rats were tested up to doses of 50 mg/kg and primates up to 20 mg/kg.

0

20000

40000

60000

Rat Primate

Area under the curve (AUC) for maximum dose tested

(hr*µg/mL)

Therapeutic Margins

AUC required for efficacy in mice (hr*µg/mL)

15x 10x

Clinical observationsHematologyClinical ChemistryCoagulationUrinalysisHistopathology

NO FINDINGS FOR:

No signs of toxicity up to the maximum doses in rats and primates


Platform expansion beyond influenza

Cloudbreak is a modular platform

This platform can be tailored to develop long acting preventative agents and potent treatments for other viral diseases. At Cidara, we have expanded the platform to address RSV, HIV and flavivirus (Dengue and Zika viruses).

Proof of concept molecules have been discovered that demonstrate highly potent in vitro activity against each of these disease vectors. These follow-on programs greatly benefit from the technologies developed in the influenza program.

INFLUENZA

HIV

RSV

DENGUEZIKA


Upcoming milestones

MidyearSTRIVE B ToplinePhase 1 sub Q

Late AugustOptions X: new Cloudbreak data

2nd half, 2019Investor Day

OctoberIDWeek/TIMM - STRIVE A&B detailed analysis

2019 2020MidyearPhase 3 topline


Financial Overview

We expect to finance our cash needs through:• equity and debt financings,• entering into collaborations, strategic

alliances and licensing arrangements,• receiving government and/or charitable

grants or contracts.

Summary Information ($ Millions) March 31, 2019

Cash $57.4

Common shares issued 26.6

Common equivalent shares issued1 32.3

1 Includes 26,641,851 common shares and assumes conversion of 565,231 shares of Series X Convertible Preferred into 5,652,310 common shares at March 31, 2019. Each share of Series X Convertible Preferred is convertible into 10 shares of common.


New Hope for Serious InfectionsCorporate PresentationJuly 2019

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Cloudbreak - Cidara Therapeutics€¦ · whether Cloudbreak candidates, including CB -012, will achieve the major attributes believed to be needed in flu such as broad spectrum, superior