Cidara Therapeutics Announces Positive Topline Results from its Phase 2b NAVIGATE Trial Evaluating CD388, a Non-Vaccine Preventative of Seasonal Influenza

Rhea-AI Summary

Cidara Therapeutics (NASDAQ: CDTX) announced positive topline results from its Phase 2b NAVIGATE trial evaluating CD388, a novel drug-Fc conjugate for preventing seasonal influenza. The trial demonstrated significant protection efficacy across all dose groups, with a single dose providing up to 76% protection over 24 weeks compared to placebo. The 450mg dose showed the highest efficacy (76.1%), followed by 300mg (61.3%) and 150mg (57.7%). The study met its primary endpoint and all secondary endpoints, including efficacy at different temperature thresholds and protection lasting up to 28 weeks. CD388 was well-tolerated across all doses with no safety concerns or drug-related serious adverse events. The company has submitted an end of Phase 2 meeting request to the FDA to discuss Phase 3 trial design.

Positive

• CD388 showed strong efficacy with 76.1% prevention rate at highest dose (450mg)
• All dose groups achieved statistically significant protection against influenza over 24 weeks
• Study met both primary and all secondary endpoints with statistical significance
• Drug demonstrated excellent safety profile with no serious adverse events
• Protection lasted up to 28 weeks with a single dose
• End of Phase 2 meeting request already submitted to FDA

Negative

• None.

Insights

Clinical Trials Expert

Cidara's CD388 shows impressive 58-76% flu prevention efficacy with single dose; Phase 3 advancement likely after strong Phase 2b results.

Cidara's Phase 2b NAVIGATE trial results for CD388 represent a significant clinical breakthrough in influenza prevention. The drug demonstrated robust efficacy across all dose groups with a clear dose-response relationship: 76.1% prevention efficacy at 450mg, 61.3% at 300mg, and 57.7% at 150mg compared to placebo over 24 weeks. All results achieved strong statistical significance (p<0.0001 for 450mg).

What's particularly impressive is the sustained protection through an entire flu season with a single dose. This contrasts sharply with seasonal vaccines which provide variable effectiveness and require annual administration. The drug maintained efficacy across different temperature threshold definitions of influenza-like illness, further validating its reliability.

The clean safety profile is equally noteworthy - no safety signals, no drug-related serious adverse events, and injection site reactions comparable to placebo. This favorable risk-benefit profile substantially increases probability of advancement to Phase 3.

For the broader context, CD388 represents a novel approach using Cidara's Cloudbreak platform to create drug-Fc conjugates. Unlike vaccines that stimulate immune responses, CD388 appears to provide direct antiviral protection irrespective of immune status, potentially addressing a critical gap for immunocompromised patients who respond poorly to vaccines.

The FDA end-of-Phase 2 meeting will be crucial for determining the Phase 3 trial design, but these robust data significantly derisk the program's regulatory pathway. The consistent efficacy across endpoints and doses suggests CD388 could become the first long-acting influenza preventative that works regardless of viral strain or patient immune status.

The study met its primary and all secondary efficacy endpoints for all dose groups

Single doses of 450mg, 300mg and 150mg of CD388 conferred 76%, 61% and 58% protection, respectively, from symptomatic influenza over 24 weeks compared to placebo

CD388 was well-tolerated with no safety signals observed

End of Phase 2 meeting request has been submitted to the U.S. Food and Drug Administration (FDA)

Cidara will host a conference call at 8:30 am ET on Monday, June 23^rd, 2025

SAN DIEGO, June 23, 2025 (GLOBE NEWSWIRE) -- Cidara Therapeutics, Inc. (Nasdaq: CDTX), a biotechnology company applying its proprietary Cloudbreak^® platform to develop drug-Fc conjugate (DFC) therapeutics, today announced positive topline results from its randomized, double-blind, placebo-controlled Phase 2b NAVIGATE trial evaluating CD388 for the prevention of seasonal influenza in healthy unvaccinated adults aged 18 to 64. The study met its primary endpoint, demonstrating a statistically significant prevention efficacy (PE) for each of three dose groups in individuals who received a single dose of CD388 at the beginning of the flu season and were evaluated for laboratory and clinically confirmed influenza over 24 weeks. The study also met all secondary endpoints, including efficacy at 37.8 and 37.2 degree Celsius temperature thresholds, as well as maintenance of PE up to 28 weeks with statistical significance. Over the same period, CD388 was well-tolerated at all doses with no unexpected dose-limiting treatment-emergent adverse events observed.

Primary Efficacy Analysis:

​	​	150 mg​ N= 1175​3 n (%)​	300 mg​ N = 1192​3 n (%)​	450 mg​ N = 1187​3 n (%)​	Placebo​ N = 1172​3 n (%)​
Primary​ Endpoint1​	Number of Participants Protocol-Defined ILI2	14 (1.2%)	13 (1.1%)	8 (0.7%)	33 (2.8%)
	Prevention Efficacy ​	57.7%	61.3%	76.1%	–
	95% CI (%)​	21.1, 78.9	27.0, 81.2	49.3, 89.9	–
	p-value​	0.0050	0.0024	<0.0001	–
ILI, influenza like illness; CI, confidence interval​ Statistical significance for grouped 300mg + 450mg dose groups was met (PE = 68.6%, p<0.0001), allowing testing of individual dose groups. ​ ILI event defined as central laboratory-confirmed RT-PCR+ influenza infection (nasopharyngeal swab), new onset of fever (oral temperature ≥38.0°C), and new onset of ≥2 respiratory symptoms (nasal congestion, sore throat, cough) or ≥1 respiratory symptom and ≥1 systemic symptom (headache, feeling feverish, body aches/pains, fatigue). Sample size (N) indicates evaluable population at time of primary analysis data cut (April 30, 2025).

Key Secondary Endpoints:

​	​	​		150 mg​ N = 11753 n (%)​	300 mg​ N = 11923​ n (%)​	450 mg​ N = 11873​ n (%)​	Placebo​ N = 11723​ n (%)​
Secondary​ Endpoints	​	Number of Participants with ≥ 37.8 °C Temp1​		15 (1.3%)	15 (1.3%)	8 (0.7%)	33 (2.8%)​
		Prevention Efficacy​		54.7%	55.3%	76.1%	–
		95% CI (%)​		16.7, 77.4	18.0, 77.8	49.3, 89.9	–
		p-value​		0.0084	0.0073	<0.0001	–
		Number of Participants with ≥ 37.2 °C Temp2​		22 (1.9%)	21 (1.8%)	12 (1.0%)	41 (3.5%)​
		Prevention Efficacy​		46.5%	49.6%	71.1%	–
		95% CI (%)​		10.2, 69.3	14.8, 71.9	45.8, 86.1	–
		p-value​		0.0148	0.0083	<0.0001	–
ILI, influenza like illness; CI, confidence interval​ CDC definition: ILI event defined as central laboratory-confirmed RT-PCR+ influenza infection (nasopharyngeal swab), new onset of fever (oral temperature ≥37.8°C), and new onset of ≥2 respiratory symptoms (nasal congestion, sore throat, cough).​ ILI event defined as central laboratory-confirmed RT-PCR+ influenza infection (nasopharyngeal swab), new onset of fever (oral temperature ≥37.2°C), and new onset of ≥2 respiratory symptoms (nasal congestion, sore throat, cough) or ≥1 respiratory symptom and ≥1 systemic symptom (headache, feeling feverish, body aches/pains, fatigue). Sample size (N) indicates evaluable population at time of primary analysis data cut (April 30, 2025).

Safety and tolerability data were similar in all arms with no safety signals observed. No drug-related serious adverse events were observed, and treatment-emergent adverse events showed no dose-dependent pattern between CD388 and placebo groups. Injection site reaction rates were similar across all CD388 dose groups and placebo.

Cidara expects to present additional results from the NAVIGATE trial at upcoming scientific conferences in 2025.

“Results such as these are unprecedented in influenza and support our confidence in the potential of CD388 to offer robust, once-per-season protection against influenza A and B,” said Jeffrey Stein, Ph.D., president and chief executive officer of Cidara. “As a long-acting antiviral drug, CD388 was designed to provide once per season protection against all strains of influenza in all people, irrespective of immune status. These results provide us with continued conviction in the remarkable opportunity CD388 presents to deliver broad influenza protection. We thank all of our collaborating partners for their dedication and hard work to reach this milestone. Cidara is grateful to the individuals whose participation helped us to generate these important results.”

Nicole Davarpanah, M.D., J.D., chief medical officer of Cidara added, "The statistically significant and clinically meaningful results shown with CD388 mark a potential breakthrough for patients and the future of influenza prevention. These Phase 2b results support the potential of CD388 to be a highly effective and well-tolerated seasonal prophylactic for high-risk individuals, such as those with compromised immune systems or those at a heightened risk of severe illness due to underlying health conditions. We look forward to engaging with the FDA and expanding on these results in our planned Phase 3 trial."

Cidara has submitted an end of Phase 2 meeting request to the FDA to review the Phase 2b results and further discuss the Phase 3 trial design and start time.

Conference Call and Webcast Details
Cidara Therapeutics management will host a conference call and webcast beginning at 8:30 am ET / 5:30 am PT today, June 23, 2025. The live webcast may be accessed here. The conference call can be accessed by dialing toll-free (877)407-4018 or (201)689-8471 (international). The conference call ID is 13754500.

A replay of the webcast will be available on the “Events & Presentations” tab in the Investors section of the company’s website.

About CD388
CD388 is an investigational drug-Fc conjugate (DFC) comprised of multiple copies of a potent small molecule neuraminidase inhibitor stably conjugated to a proprietary Fc fragment of a human antibody. DFCs are not vaccines or monoclonal antibodies but are low molecular weight biologics which are designed to function as long-acting small molecule inhibitors. CD388 was designed to provide universal protection against all known strains of seasonal and pandemic influenza with the potential to provide season-long protection with a single subcutaneous or intramuscular administration. Importantly, because CD388 is not a vaccine, its activity is not reliant on an immune response and thereby is expected to be efficacious in individuals regardless of immune status. More information can be found at: https://www.cidara.com/cloudbreak/influenza/.

About Phase 2b NAVIGATE Trial
The Phase 2b NAVIGATE clinical trial (NCT06609460) is a randomized, double-blind, controlled trial in more than 5,000 healthy, unvaccinated adult participants across clinical sites in the U.S. and U.K. who are not at risk of complications from influenza. The objective of the study was to evaluate safety, pharmacokinetics and the rates of laboratory and clinically confirmed influenza in participants receiving single doses of CD388 (150mg, 300mg, 450mg) or placebo administered once at the beginning of the flu season. Participants were followed for the remainder of the influenza season to monitor for breakthrough cases. Protocol-defined PE was determined by the percentage by which the CD388 treated groups reduced the rates of symptomatic influenza infection compared to the placebo group.

About Cidara Therapeutics
Cidara Therapeutics is using its proprietary Cloudbreak^® platform to develop novel drug-Fc conjugates (DFCs) comprising targeted small molecules or peptides coupled to a proprietary human antibody fragment (Fc). Cidara’s lead DFC candidate, CD388, is a long-acting antiviral designed to achieve universal prevention of seasonal and pandemic influenza with a single dose by directly inhibiting viral proliferation. In June 2023, CD388 was granted Fast Track Designation by the U.S. Food and Drug Administration (FDA), and the Company announced completion of enrollment of its Phase 2b NAVIGATE trial in December 2024. Additional DFCs have been developed for oncology and in July 2024 Cidara received investigational new drug application clearance for CBO421 which is intended to target CD73 in solid tumors. Cidara is headquartered in San Diego, California. For more information, please visit www.cidara.com.

Forward-Looking Statements

This release contains “forward-looking statements” within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, and such forward-looking statements are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. “Forward-looking statements” describe future expectations, plans, results, or strategies and are generally preceded by words such as “anticipates,” “expect,” “intends,” “believes,” “may,” “plan” or “will”. Forward-looking statements in this release include, but are not limited to, statements related to the potential benefits of and future plans for CD388, plans for engaging with the FDA and the impact of such discussions, a planned Phase 3 trial of CD388 and the expected timing for presenting additional results from the NAVIGATE trial. Such statements are subject to a multitude of risks and uncertainties that could cause future circumstances, events, or results to differ materially from those projected in the forward-looking statements, such as unanticipated delays in or negative results from Cidara’s clinical trials and other risks related to clinical development, delays in action by regulatory authorities, other obstacles on the enrollment of patients or other aspects of CD388 or other DFC development and other risks and uncertainties associated with Cidara’s business in general. These and other risks are identified under the caption “Risk Factors” in Quarterly Report on Form 10-Q for the quarterly period ended March 31, 2025 and other filings subsequently made with the SEC. All forward-looking statements contained in this press release speak only as of the date on which they were made and are based on management’s assumptions and estimates as of such date. Cidara does not undertake any obligation to publicly update any forward-looking statements, whether as a result of the receipt of new information, the occurrence of future events or otherwise.

INVESTOR CONTACT:
Brian Ritchie
LifeSci Advisors
(212) 915-2578
britchie@lifesciadvisors.com

MEDIA CONTACT:
Michael Fitzhugh
LifeSci Communications
(628) 234-3889
mfitzhugh@lifescicomms.com

FAQ

What were the efficacy rates for different doses of Cidara's CD388 in the Phase 2b trial?

The 450mg dose showed 76.1% efficacy, 300mg showed 61.3% efficacy, and 150mg showed 57.7% efficacy in preventing symptomatic influenza over 24 weeks compared to placebo.

How long does the protection from Cidara's CD388 influenza treatment last?

CD388 demonstrated protection efficacy for up to 28 weeks (about 7 months) with a single dose, maintaining statistical significance throughout this period.

What were the safety results for CDTX's CD388 in the Phase 2b NAVIGATE trial?

CD388 was well-tolerated across all dose groups with no safety signals, no drug-related serious adverse events, and injection site reaction rates similar to placebo.

What is the next step for Cidara Therapeutics' CD388 development?

Cidara has submitted an end of Phase 2 meeting request to the FDA to review the Phase 2b results and discuss the Phase 3 trial design and start time.

How does Cidara's CD388 differ from traditional flu vaccines?

CD388 is a non-vaccine, long-acting antiviral drug designed to provide once-per-season protection against all strains of influenza A and B, regardless of the person's immune status.