Acurx Pharmaceuticals, Inc. (NASDAQ:ACXP) is a clinical-stage biopharmaceutical company focused on developing a novel class of antibiotics to address serious or life-threatening bacterial infections. The company's lead product candidate, ibezapolstat, is currently in late-stage clinical development for the treatment of Clostridioides difficile infection (CDI), a debilitating and potentially deadly condition.

Business Overview

Acurx Pharmaceuticals was founded in 2017 and acquired the rights to ibezapolstat, its lead antibiotic candidate, in February 2018. The company's primary focus is on developing ibezapolstat, which targets the treatment of CDI, a Gram-positive bacterial infection that is classified as an urgent threat by the U.S. Centers for Disease Control and Prevention (CDC). CDI is a significant public health concern, with an estimated annual cost burden of $4.7 billion on the U.S. healthcare system.

Ibezapolstat is a first-in-class antibiotic that works by inhibiting the DNA polymerase IIIC (pol IIIC) enzyme, a previously unexploited scientific target. This novel mechanism of action differentiates ibezapolstat from currently available CDI treatments, which primarily target the symptoms of the infection rather than the underlying cause. Acurx's research has shown that ibezapolstat is effective in treating CDI while also preserving the patient's gut microbiome, which is crucial for preventing recurrent infections.

Recent Developments and Clinical Progress

In the first quarter of 2024, Acurx made significant progress in the development of ibezapolstat. The company announced positive comparative microbiology and microbiome data from the Phase 2b clinical trial segment, which showed that ibezapolstat outperformed the standard of care, vancomycin, in eradicating fecal C. difficile at day three of treatment. Additionally, ibezapolstat was found to consistently preserve and allow the regrowth of key gut bacterial species believed to confer health benefits and prevent recurrent CDI.

Following these promising results, Acurx held an end-of-Phase 2 meeting with the U.S. Food and Drug Administration (FDA) in April 2024. During this meeting, the company reached agreement with the FDA on the key elements of its Phase 3 clinical program, including the design, statistical analysis, and regulatory pathway for a New Drug Application (NDA) filing. The FDA confirmed that Acurx is ready to proceed to Phase 3 trials, which the company plans to initiate in the fourth quarter of 2024.

Acurx also received approval from the European Medicines Agency (EMA) to be designated as a small to medium-sized enterprise (SME) in Europe, which provides for certain benefits, including fee reductions and other support from the Agency for seeking a marketing authorization in Europe.

Financials

For the fiscal year ended December 31, 2023, Acurx reported a net loss of $14.6 million and no revenue, as the company is still in the clinical development stage and has not yet generated any product sales. The company's annual operating cash flow and free cash flow were both negative $9.8 million.

In the first quarter of 2024, Acurx reported a net loss of $4.4 million, or $0.28 per diluted share, compared to a net loss of $2.9 million, or $0.25 per diluted share, in the same period of the prior year. Research and development expenses for the quarter were $1.6 million, up from $1.0 million in the first quarter of 2023, primarily due to an increase in manufacturing-related costs. General and administrative expenses were $2.8 million, up from $1.9 million in the prior-year quarter, driven by a $0.7 million increase in professional fees and a $0.2 million increase in non-cash share-based compensation.

Liquidity

As of March 31, 2024, Acurx had cash of $8.9 million, compared to $7.5 million as of December 31, 2023. The company raised additional funds during the first quarter of 2024 through its at-the-market (ATM) financing program, selling 1,121,793 shares for gross proceeds of approximately $4.4 million.

Regulatory Pathway and Commercialization Strategy

Acurx's ibezapolstat has been granted Fast Track designation by the FDA for the treatment of CDI, reflecting the urgent need for new antibiotic therapies to address this serious infection. The company's discussions with the FDA have provided a clear regulatory roadmap for the Phase 3 clinical program, which will consist of two non-inferiority trials versus the current standard of care, vancomycin.

The Phase 3 trials are expected to enroll a total of approximately 900 patients (450 per trial) in the modified intent-to-treat (MITT) population. Acurx anticipates that the Phase 3 program will take 18 to 24 months to complete, with the first trial expected to begin enrollment in the fourth quarter of 2024.

Upon successful completion of the Phase 3 trials and regulatory approval, Acurx plans to commercialize ibezapolstat in the United States with its own specialized sales force. The company is also actively exploring partnership opportunities for the development and commercialization of ibezapolstat in other global markets, such as Europe, the United Kingdom, Japan, and Canada.

Market Opportunity and Competitive Landscape

CDI is a significant public health concern, with the CDC classifying it as an urgent threat. The disease affects approximately 500,000 patients annually in the United States, with a recurrence rate of up to 35%. The current standard of care, vancomycin, has limitations, including the potential for disruption of the gut microbiome and a recurrence rate of approximately 20%.

Ibezapolstat's novel mechanism of action, which targets the pol IIIC enzyme, has the potential to address these limitations and provide a more effective treatment option for patients with CDI. If approved, ibezapolstat would be the first new class of antibiotics brought to the market in over three decades, positioning it to capture a significant share of the estimated $1 billion global CDI market.

Acurx faces competition from other companies developing CDI treatments, such as Seres Therapeutics, Finch Therapeutics, and Rebiotix (a Ferring Pharmaceuticals company). However, ibezapolstat's unique mechanism of action and the positive results from the Phase 2 clinical trials suggest that it could differentiate itself in the market.

Risks and Challenges

As with any clinical-stage biopharmaceutical company, Acurx faces several risks and challenges, including the inherent uncertainties of drug development, the potential for delays or failures in clinical trials, regulatory approval hurdles, and competition from other market participants. The company's ability to successfully navigate these challenges and execute its development and commercialization strategy will be crucial to its long-term success.

Additionally, Acurx will need to secure additional funding to support the Phase 3 clinical trials and prepare for the potential commercialization of ibezapolstat. The company is actively exploring partnership opportunities and other financing options to ensure it has the necessary resources to advance its lead candidate through the final stages of development and regulatory approval.

Conclusion

Acurx Pharmaceuticals is a promising clinical-stage biopharmaceutical company with a novel antibiotic candidate targeting a significant unmet medical need in the treatment of CDI. The positive results from the Phase 2 clinical trials, the company's clear regulatory pathway for Phase 3 development, and the potential for ibezapolstat to address the limitations of current CDI treatments make Acurx an intriguing investment opportunity in the antibiotics space. As the company continues to execute on its development and commercialization strategy, investors will closely monitor its progress and the potential for ibezapolstat to become a valuable new treatment option for patients with this serious and debilitating infection.