Pioneering New Solutions for Challenging Pathogens with Innovative Therapies and Patient-centric Care!

 

Antibiotic resistance is a growing concern in the medical community, with more and more bacteria becoming resistant to existing treatments. One particularly dangerous bacteria is Clostridioides difficile, or C. diff. This bacteria can cause severe and life-threatening infections, especially in vulnerable populations such as the elderly or immunocompromised patients. Developing new antibiotics to treat C. diff infections is a critical need, and Acurx Pharmaceuticals is on a mission to do just that.

Acurx Pharmaceuticals is a biopharmaceutical corporation that is dedicated to the development of a novel type of antibiotic intended to combat infections induced by C. diff. In contrast to the traditional approach to antibiotic development, Acurx's strategy involves the targeting of a completely new molecular target called the DNA polymerase IIIC enzyme (Pol IIIC). This particular enzyme is indispensable for bacterial DNA replication, and by seeking to target it, Acurx aspires to create a fresh form of antibiotic that will be efficacious against C. diff infections.

David P. Luci, the co-founder and Chief Executive Officer of Acurx Pharmaceuticals, is revolutionizing the field of antibiotic discovery by identifying and targeting a previously unexplored molecular target, the DNA polymerase IIIC enzyme. By laser-focusing on this distinctive target, Acurx is opening up novel pathways for the development of potent antibiotics to efficaciously combat infections caused by C. difficile and other gram-positive bacteria, including MRSA. This innovative approach has the potential to transform the treatment landscape and instill optimism in patients grappling with these arduous infections.

Leading Acurx's antibiotic development is ibezapolstat, an innovative therapy engineered to combat C. difficile infections. As the company's premier candidate, ibezapolstat signifies a noteworthy leap forward in the battle against this chronic and frequently relapsing ailment. Acurx Pharmaceuticals is dedicated to progressing ibezapolstat through meticulous clinical trials, with the ultimate objective of acquiring FDA endorsement and rendering this revolutionary treatment accessible to necessitous patients.

Acurx Pharmaceuticals comprehends the significance of diversifying its pipeline to tackle the ever-changing obstacles presented by antibiotic-resistant infections. Alongside ibezapolstat, the corporation has formulated ACX-375, a hopeful contender aimed at addressing the treatment of MRSA infections. By expanding its collection of polymerase IIIC inhibitors, Acurx is actively meeting the pressing demand for efficient antibiotics to counteract various gram-positive bacterial infections. Their devotion to novelty and patient-focused resolutions distinguishes them from their peers in the pharmaceutical sector.

Acurx Pharmaceuticals has consistently been steered by a strategic vision that entails delving into partnership prospects while upholding a resolute commitment to its drug development programs. With a history of triumphs in past endeavors, Acurx adopts a "De-risking strategy" that guarantees persistent advancement throughout clinical trials, even as they examine conceivable partnership discussions. The establishment's ultimate objective is to introduce its ground-breaking antibiotic remedies to the market, guaranteeing the utmost level of patient care and enhancing global health consequences.

Acurx, under the guidance of a visionary leadership team, including the esteemed David P. Luci, is at the forefront of rewriting the narrative in antibiotic discovery and treatment.

 

In this exclusive cover story, we delve into Acurx's roadmap for antibiotic discovery, its groundbreaking approach, and its dedication to improving patient outcomes!

 

The Inspiring Story of Acurx Pharmaceuticals' Mission

The inception of the corporation transpired in February of 2018 when they procured ibezapolstat, their primary antibiotic candidate, from a body formed by two retiring research scientists who uncovered this innovative molecule while working at the prestigious University of Massachusetts. The initial objective was to create an unprecedented class of antibiotics that would be effective in treating infections caused by gram-positive bacteria such as C. diff, MRSA, and other related strains. The first order of business was to develop ibezapolstat for C. diff infections, followed by expanding their pipeline of polymerase IIIC inhibitors. Their latest addition to the pipeline is ACX-375, which targets the treatment of infections caused by MRSA. This "Home-grown" product candidate was discovered and developed after their inception.

Incorporated into their initial business plan was a thorough investigation of advantageous possibilities for the company following the successful conclusion of their intended Phase 2b clinical trial program. However, they possess the expertise and inclination to persist with ibezapolstat's development until it acquires FDA approval and completes the marketing period, provided that partnership discussions do not yield a favorable transaction alternative as deemed by their board of directors. This strategy mirrors their prior co-founded ventures and has gained recognition in the media as a "De-risking strategy". Acurx Pharma, in this particular instance, functions as an incubator company that carries out clinical trials to advance the program from drug discovery to Phase 3 clinical trials.

 

Fast Track to Success

The odyssey up to this point has been rather exhilarating and superior to expectations on numerous fronts, despite encountering formidable obstacles along the way. The most conspicuous obstacle has been the COVID-19 pandemic and its influence on clinical trials at large, and C. difficile trials in particular. This has necessitated significant attention and effort from management, which has devised innovative methodologies or ones they had not previously encountered, to surmount the challenges posed by the pandemic milieu. Despite this, a series of unanticipated victories have presented a splendid opportunity for their product, public health, and their stakeholders and have unquestionably galvanized their team.

 

Celebrating the Milestones

During their research, the team made several notable discoveries, including the fortuitous finding that the administration of ibezapolstat can effectively restore the microbiome in patients afflicted by C. difficile infection, either directly or indirectly. This unexpected second dimension of their work was a welcome surprise, as was the realization that their treatment protocol was associated with a favorable secondary-to-primary bile acid ratio, significantly reducing the risk of reinfection post-treatment. Another significant asset was the profound impact of the Dutch government's contribution to their understanding of the mechanism of action of polymerase IIIC inhibitors, which has played a pivotal role in guiding the development of their product pipeline.

The emergence of public-private partnerships concerning antibiotic development, including the initiatives by the Repair Impact Fund and AMR Action Fund, and the introduction of "Pull incentives" which have already been sanctioned in the U.K. and are being considered in the U.S., were unforeseeable developments. Taken together, these factors had an overall beneficial effect, despite navigating their modest vessel directly through the midst of the COVID pandemic.

 

Revolutionizing the Fight Against Bacterial Infections

A novel class of antibiotics dubbed polymerase IIIC inhibitors is in the process of development. These inhibitors target the Pol IIIC enzyme, which is the chief catalyst for DNA synthesis in newly created C. difficile bacteria and other gram-positive bacteria. The Pol IIIC enzyme is exclusively present in specific gram-positive bacterial cells, which renders their antibiotic candidate innocuous to healthy cells.

 

Ibezapolstat

Ibezapolstat, formerly known as ACX-362E, has progressed to the Phase 2b clinical trial stage in patients afflicted with C. difficile infection following its successful completion of Phase 2a clinical trials by the close of 2021. The Phase 2a clinical trial was brought to an early end on account of its victorious outcome, with all 10 patients being completely cured of the C. difficile infection. Furthermore, all of them experienced sustained clinical cures for 30 days after the treatment had ended, thereby precluding any chances of reinfections and demonstrating a success rate of 100%.

Based on this information, the scientific advisory board advised the premature termination of the Ph2a trial and the progression to the Ph2b trial, which was carried out in December 2021. Subsequently, the FDA has approved their Interim Analysis Plan, enabling the newly established Independent Data Monitoring Committee to evaluate the clinical effectiveness data of the Ph2b trial with only 36 patients enrolled.

 

New Clinical Development Opportunities

The FDA has bestowed upon ibezapolstat (previously known as ACX-362E) a "Fast track" designation. Their clinical development strategies incorporate seeking, at the appropriate juncture, both QIDP status and Fast Track designation for their second antibiotic contender, ACX-375, which specifically targets MRSA infections.

Their efforts in the drug discovery phase of development persist as they seek to unearth novel Pol IIIC inhibitors to bolster their pipeline, in addition to ibezapolstat and ACX-375. The efficacy of targeting Pol IIIC in a clinical setting has been confirmed by their Ph2a clinical trial, which achieved a 100% cure rate without any instances of reinfection.

 

The industry with Unmatched Differentiators

There are a few noteworthy aspects to consider. Firstly, the company's business strategy entails running a virtual model for as long as feasible until the marketing phase. This approach serves as a de-risking measure, as discussed earlier. Should they enter the Ph3 trials, they will undoubtedly recruit personnel to facilitate a seamless transition to a lucrative marketing launch. They are keen on avoiding past occurrences where companies have incurred significant cash burn with no revenue, metaphorically referred to as "Drinking the cool aid" before reaching breakeven.

Without explicitly mentioning any specific antibiotic firms that have suffered this fate, he emphasizes the importance of steering clear of such scenarios. Acurx has been fortunate enough to have its data continually improve while witnessing other companies, such as Pfizer, Sanofi, Summit, and Finch, face setbacks. This juxtaposition only highlights the success of Acurx's data.

It is believed that the efficacy of ibezapolstat is attributed to its mechanism of action, which is currently being explored by researchers in collaboration with their colleagues at Leiden University Medical Center in Holland. The study reveals that ibezapolstat can restore the microbiome and maintain a highly desirable secondary-to primary bile acid ratio. Furthermore, the researchers are planning to unveil other favorable properties of ibezapolstat in Copenhagen in April 2023 through two presentations. It is noteworthy that ibezapolstat reaches the infection site at a concentration that is over 100 times greater than the amount required to eliminate the C. diff bacteria, which is a positive indication. The majority of these favorable properties were unforeseeable at the commencement of the program.

 

Secrets of a High-Performance Work Culture

Their top priority lies in achieving significant advancement in their development programs while ensuring sufficient resources to attain their key value inflection points. Despite the pandemic, their "Fundamentals" have become even more robust and diversified. Nevertheless, the past three years have presented a significant challenge, as market dislocation, a faltering economy, inflation, worldwide social and political strife, and the pandemic have made capital raising increasingly difficult. Nonetheless, this predicament is not exclusive to Acurx, and they believe they are suitably equipped to maneuver through these trying times.

 

Bob DeLuccia's Journey in the Pharmaceutical Industry

The esteemed executive chairman, Bob DeLuccia, embarked on his illustrious career in 1972 at Pfizer and has astutely introduced countless antibiotics over the course of his 30-year tenure in the pharmaceutical realm, evidencing his adeptness in both product innovation and marketing tactics. His vast erudition and extensive connections have been instrumental in assembling a high-caliber Research and Development (R&D) team, Scientific Advisory Board, and Independent Data Monitoring Committee to supervise its R&D pipeline and projects. These valuable resources are the foundational pillars for their unrelenting pursuit of excellence in research and development.

 

Innovation Odds

Pioneering innovation in any given clinical indication poses a formidable challenge since institutional investors perceive greater developmental risks in a program that is unprecedented until there is at least proof of concept in human clinical trials. This challenge is particularly stark in the realm of antibiotics, as only a small fraction of institutional investors evince interest in this sector, compared with investing in pharmaceutical research and development in more lucrative spheres such as oncology and diabetes. This reality could shift if the Pasteur Act or DISARM Act is sanctioned by the government, but for the present, it remains the status quo, even as the CDC and WHO plead with innovators to devise novel classes of antibiotics.

During the nascent phase of an antibiotic development incubator like Acurx, procuring meetings can prove to be a formidable task. However, as the trials proceed to the latter stages, the momentum gains traction, and it becomes comparatively effortless to amass capital. The primary sponsors of the initial capital are chiefly the co-founders themselves, and subsequently, if significant improvements are witnessed, angel investors step in to provide further funding.

 

Mapping Out Long-term Goals and Short-term Plans

The company's overarching objective is to harness its expertise and resources to create novel antibiotic candidates. These candidates will be sourced from major research facilities in the United States. The aim is to "De-risk" the assets by conducting late-stage clinical trials and obtaining FDA or EMA approval. Ultimately, the company will partner with pharmaceutical companies to bring these innovative drugs to market. By doing so, the company will provide a critical service to patients and public health, as the use of antibiotics will be prolonged, and life-threatening infections can be effectively treated. In the short term, the company is focused on completing the enrollment process for its Ph2b trial, which aims to treat patients with C. difficile. The company is simultaneously exploring strategic alternatives and will select the most promising project based on the board of directors' determination.