Immunotherapy Platform May 2019

© Cidara Therapeutics 2019 0

CloudbreakImmunotherapy PlatformMay 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 incidence of invasive fungal infections and related mortality rates, effectiveness and limitations of current therapies; potential market sizes for rezafungin, ability of rezafungin to capture market share from existing therapies, and the advantages of rezafungin in other settings of care. Statements regarding the effectiveness and safety of our antiviral Fc conjugates (AVCs) or any other potential attributes of our AVCs; the potential of our AVCs to treat and/or prevent infections, and the degree to which in vitro results and results in animal models with our AVCs predict results in humans, and other attributes of and plans for our AVCs; as well as the incidence of influenza and related mortality rates, and the effectiveness and limitations of current influenza therapies are also forward-looking. 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 industry.

These 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 ability to 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.


Cloudbreak Antiviral Conjugates (AVCs) are not conventional antibody-drug conjugates (ADCs)

While the Cloudbreak platform was inspired by oncology immunotherapies, the approach is fundamentally different

Instead of using an antibody directed to a a tumor cell specific epitope to deliver a toxic payload to the cell, Cloudbreak molecules use an antimicrobial drug called a targeting moiety (TM) to bind to conserved, essential cell surface targets on the pathogen. The effector moiety (EM) portion of the molecule is the Fc domain of a human antibody which engages an immune response and imparts prolonged “antibody-like” PK to the molecule in vivo. The intrinsic antimicrobial activity of the conjugate allows it to retain activity even in immune compromised hosts.

Oncology ADC using an antibody to deliver a toxic payload to a cancer cell.

Cloudbreak antiviral Fc conjugates (AVCs) use a novel antiviral drug (TM) to provide direct pathogen killing and to deliver an Fc antibody fragment domain (EM) to a pathogen for a focused immune response.

Targeting Moiety (TM)

Effector Moiety (EM)


Vaccines

Monoclonal Antibodies

Traditional Antivirals

3

AVCs are novel, and highly differentiated

AVCs are not…


• 25 to 50 million influenza cases/yr• 2-3 fold increase in pneumonia• $25B in health care costs (US)

Influenza remains a major medical challenge

Despite the availability of vaccines and therapeutics, influenza and related complications remain a major cause of hospitalizations and attendant healthcare costs annually in the US

Thompson WW, et al. Influenza Other Respir Viruses. 2009; 3(1): 37-49Thompson WW, et al. JAMA. 2004; 292(11):1333-4CDC. MMWR Morb Mortal Wkly Rep. 2010; 59(33):1057-62

226,000 HOSPITALIZATIONS (US)

80,000 Americans died from flu in the 2017-2018 flu season, the highest death toll in 10 years


Vaccines are trying to hit a moving target

According to the CDC, vaccines are 40% effective on average

Over the course of the six-month manufacturing period of influenza vaccines, the initial targeted strains mutate which renders the vaccine only partially effective. In addition, vaccines typically work against Influenza A strains and not influenza B. In patient populations with weakened immune systems, like the elderly, vaccine efficacy is even lower.

Initial strains -> Six month manufacturing -> Mutated strains

https://www.cdc.gov/flu/professionals/vaccination/effectiveness-studies.htm

H3N2 is a problematic strain – vaccine coverage is < 25%


Therapeutics target more highly conserved regions

2xDaily

A narrow treatment window of influenza drugs limits clinical utility

Influenza drugs such as Tamiflu® are highly effective. However, the window of efficacy is limited to 48 hours post symptoms.

The recent approval of Xofluza™ (Baloxavir) provides protection with a single dose, as opposed to the twice-daily dosing of Tamiflu. However, the 48-hour window of treatment post-symptoms, as well as the time to alleviation of symptoms (54 hours), remains unchanged from Tamiflu. Also, the median time to alleviation of symptoms in patients with influenza B treated with Xofluza was no better than those treated with placebo. Clearly, there is still substantial room for improvement.

48 HOURS


Cloudbreak AVCs combine the advantages of small molecules (SMs) and monoclonal antibodies

VIRUS

• High potency SMs

• Extended half-life

• Broad spectrum (’flu A&B)

• Combining multiple MOAs

Conserved, essential target

Intrinsic antiviral activity


Cloudbreak AVCs have highly potent in vitro activity

Cloudbreak AVCCB-012 has potent activity against both seasonal and pandemic strains of influenza

H1N1 is a swine flu strain that is frequently used in laboratory studies. It is able to replicate in mammalian cells from multiple species

H3N2 is a high pathogenicity strain that can infect birds and mammals. It is increasingly abundant in seasonal flu

This strain was responsible for the 2009 flu pandemic. Caused 600,000 deaths

This is a seasonal Flu B strain. It has limited susceptibility to Tamiflu and Xofluza

H5N1 is a highly pathogenic avian strain. There is concern that it could acquire mutations to become a human pandemic strain


AVC in vitro potency and spectrum translates in vivo

Single low doses of CB-012 protect mice against multiple influenza strains in lethal infection models

5 mice per cohort CB-012 dosed 4 hours prior to infection

100%

0%

0 14Days

Surv

ival

CB-012 0.4 mg/kg

A/Texas/36/91 H1N1

Neg control (Fc only) 14Days

100%

0%

0

Surv

ival

A/Hong Kong/1968 H3N2

CB-012 0.4 mg/kg

14Days

100%

0%0

Surv

ival

B/Malaysia/04

CB-012 0.4 mg/kg

Dose


AVCs retain activity against drug resistant strains

A single low dose of CB-012 protects mice against a lethal infection model with oseltamivir resistant H1N1

A/Perth/261/2009 H1N1 (H275Y)

14Days

100%

0%

0

Surv

ival

Neg control (Fc only)

Oseltamivir 20mg/kg BID x 5

CB-012, 2 mg/kg, 1 doseA single low dose of CB-012 protects mice against a lethal infection model with oseltamivir resistant H1N1


AVCs improve the treatment window versus Tamiflu in preclinical efficacy models

In vivo treatment models suggest that AVCs could be effective for treatment of influenza

In this lethal mouse model of H1N1, single IV doses of CB-012 administered out to 72 hours post-infection offer significant protection from mortality

5 mice per cohort. Tamiflu dosed BID for 5 days in each cohort


AVCs demonstrates extended half-life

A key attribute of AVCs is their remarkable half-life.

The prolonged half-life, coupled with high potency, enables multiple clinical development options

In the clinic we plan to evaluate the potential for a “once and done” prophylactic administration that could provide protection for the entire flu season

CB-012 demonstrated similar bioavailability via multiple dosing routes: IV, SC, IM


Extended half-life translates to long duration of action for prevention

The high potency and long half-life of Cloudbreak anti-influenza molecules positions them well as long acting prevention agents

In this lethal mouse model of H1N1, a single IV doses of CB-012 administered 28 days prior to infection provided 100% protection from mortality at doses down to 2.5 mg/kg


AVCs demonstrate robust safety in rat

Preclinical toxicity studies indicate a potential for a broad safety margin with no signs of acute or chronic toxicity at over 15-fold the efficacious dose in prophylactic efficacy models

CB-012 14 day dose-range study• Dosed twice: days 0 and 7• Tested (IV) at 5, 20 and 50 mg/kg

Clinical observationsHematologyClinical ChemistryCoagulationUrinalysisHistopathology

NO FINDINGS

Therapeutic margin

>15X


AVCs demonstrate robust safety in cynomolgus monkey

Preclinical toxicity studies indicate a potential for a broad safety margin with no signs of acute or chronic toxicity at over 10-fold the efficacious dose in prophylactic efficacy models

CB-012 14 day dose-range study• Dosed twice: days 0 and 7• Tested (IV) at 5, and 20 mg/kg

Clinical observationsHematologyClinical ChemistryCoagulationUrinalysisHistopathologyCytokine profiling

NO FINDINGS

Therapeutic margin

>10X


Cloudbreak AVCs: Ongoing and planned activities

16

NEXT STEPS

• Development candidate• IND-enabling studies

10

100

1000

0 50 100 150 200Mea

n Pl

asm

a C

onc

(ug/

mL)

Time (hr)

14Days

100%

0%0

Surv

ival



CB-012, 2 mg/kg, 1 dose


Cloudbreak AVCs: Ongoing and planned activities

17

NEXT STEPS

• Development candidate• IND-enabling studies

14Days

100%

0%

0

Surv

ival



CB-012, 2 mg/kg, 1 dose

100%

0%

0 14Days

Surv

ival

CB-012, 2.5 mg/kg, 1 dose

-28

Dose

Infect


Financial Overview

Summary Information ($ Millions) 3/31/2019

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 PresentationMay 2019

Immunotherapy Platform May 2019

Documents

Transcript of Immunotherapy Platform May 2019