Cloudbreak. March Cidara Therapeutics

Transcription

1 Cloudbreak March 2019 Cidara Therapeutics

2 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 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, longacting 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 ADCs or any other potential attributes of our ADCs; the potential of our ADCs to treat and/or prevent infections, and the degree to which in vitro results and results in animal models with our ADCs predict results in humans, and other attributes of and plans for our ADCs; 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: the success and timing of Cidara s preclinical studies, clinical trials and other research and development activities; regulatory developments in the United States and foreign countries; changes in Cidara s plans to develop and commercialize its product candidates; Cidara s ability to obtain additional financing; 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. Cidara Therapeutics

3 Cloudbreak immunotherapy platform Rezafungin Cloudbreak Cidara Therapeutics

4 Cloudbreak is not a conventional antibody-drug conjugate (ADC) 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 to bind to conserved, essential cell surface targets on the pathogen. The antibody 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 in immune compromised hosts. Oncology ADC using an antibody to deliver a toxic payload to a cancer cell Cloudbreak ADC using an antimicrobial drug to provide direct pathogen killing and to deliver an Fc antibody domain to a pathogen for a focused immune response Cidara Therapeutics

5 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 25 to 50 million influenza cases/yr 2-3 fold increase in pneumonia $25B in health care costs (US) 226,000 HOSPITALIZATIONS (US) 80,000 Americans died from flu in the flu season, the highest death toll in 10 years Thompson WW, et al. Influenza Other Respir Viruses. 2009; 3(1): Thompson WW, et al. JAMA. 2004; 292(11): CDC. MMWR Morb Mortal Wkly Rep. 2010; 59(33): Cidara Therapeutics

6 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 H3N2 is a problematic strain vaccine coverage is < 25% Cidara Therapeutics

7 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. Therapeutics target more highly conserved regions 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. 2x Daily 48 HOURS Cidara Therapeutics

8 Cloudbreak combines the advantages of small molecules (SMs) and monoclonal antibodies High potency SMs Extended half-life Broad spectrum ( flu A&B) Combining multiple MOAs Intrinsic antiviral activity VIRUS Conserved, essential target Cidara Therapeutics

9 Cloudbreak has highly potent in vitro activity Cloudbreak antiinfluenza molecules have 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 Cidara Therapeutics

10 Cloudbreak has highly potent in vivo activity In vivo models enable the assessment of both the antiviral TM as well as the immune engagement of the Fc EM of the Cloudbreak anti-influenza molecules 5 mice per cohort CB-012 dosed 4 hours prior to infection, Tamiflu dosed 8 hrs post infection In this lethal mouse model of H1N1, a single dose of CB-012 provided 100% protection at 1/500 th the cumulative amount of Tamiflu administered over 10 doses Cidara Therapeutics

11 Body weight data supports robust efficacy & safety Body weights of mice from in vivo efficacy experiments provide a sensitive measure of drug tolerability and response to disease. CB-012 Average Body Weights Influenza A (H1N1; TX/36/91) CB-012 (0.4 mpk) Tamiflu (20 mpk) CB-012 (50 mpk) In the lethal mouse model described on the prior slide the body weights of mice in the negative control, Tamiflu and CB-012 cohorts were measured over the course of the 14-day experiment. All negative control mice died by day six, succumbing to the disease Negative control The Tamiflu cohort lost 15% of body weight upon discontinuation of treatment, indicating that the influenza virus was not eradicated. Body weights recovered as the mouse immune system overcame the disease Both the lowest and highest dose cohorts of CB-012 maintained stable weights over the course of the experiment, indicating that the low dose prevented disease progression and the high dose was well tolerated Cidara Therapeutics

12 Cloudbreak improves the treatment window versus Tamiflu in preclinical efficacy models In vivo treatment models suggest that Cloudbreak antiinfluenza molecules could be effective for treatment of influenza 5 mice per cohort. Tamiflu dosed BID for 5 days in each cohort 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 Cidara Therapeutics

13 Cloudbreak demonstrates extended half-life A key attribute of Cloudbreak anti-influenza lead molecules is their remarkable half-life. The prolonged half-life, coupled with high potency, enables multiple clinical development options Mean Plasma Conc (ug/ml) Mouse PK 50 mg/kg IV injection days: days: Mouse half-life Projected human half-life Time (hr) 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 Cidara Therapeutics

14 Extended half-life translates to long duration of action for prevention The high potency and long half-life of Cloudbreak antiinfluenza molecules positions them well as long acting prophylactic 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 Cidara Therapeutics

15 Preliminary safety results are consistent with high therapeutic index Preclinical toxicity studies indicate a potential for a broad safety margin with no signs of acute or chronic toxicity at over 100-fold the efficacious dose in prophylactic efficacy models Cidara Therapeutics

16 Ongoing and planned activities CB-012, 0.4 mg/kg, 1 dose 100% NEXT STEPS Survival 0% 0 Days 14 Development candidate IND-enabling studies Mean Plasma Conc (ug/ml) Time (hr) Cidara Therapeutics

17 Cloudbreak March 2019 Cidara Therapeutics