RECCE® 327 Treatment
Recce Pharmaceuticals Ltd.'s anti-infective pipeline includes patented, broad-spectrum, synthetic polymer RECCE® 327 (R327), an intravenous and topical therapy being developed for the treatment of severe and potentially life-threatening infections caused by both Gram-positive and Gram-negative bacteria, including their superbug forms, such as Urinary Tract Infections (UTIs), which are common infectious diseases caused by pathogens, such as Escherichia coli (E. coli) (62%). Recce's anti-infectives are wholly synthetic, based on a patented polymeric structure, and designed to overcome resistance. Recce's anti-infectives can potentially overcome the hypercellular mutation of bacteria and viruses, which is the challenge of all existing antibiotics. R327 affects the assembly of bacterial cell division complex components that require cellular energy to remain assembled, confirming its ability to disrupt cellular bioenergetics. This decreases the formation of the bacterial cell division complex into ring-like structures (Z-rings) in a concentration-dependent manner. RECCE® 327 is not a UTI preventive vaccine.
The U.S. Food and Drug Administration (FDA) has awarded RECCE® 327 Qualified Infectious Disease Product designation under the Generating Antibiotic Initiatives Now (GAIN) Act, labeling it for Fast Track Designation, plus ten years of market exclusivity post approval. On May 7, 2024, Recce announced that the China National Intellectual Property Administration Granted a new Patent Family 2 for Recce's anti-infectives, "Copolymer and Method for Treatment of Bacterial Infections" in China, expiry 2035.
According to the World Health Organization (WHO), RECCE® 327 was added to the WHO List of Antibacterial Products in Clinical Development on June 18, 2024. R327 is the only compound classified as an adenosine triphosphate (ATP) production disruptor. Disruption of ATP production in bacterial cells, when targeted as the primary mechanism of action, not secondary to other cell perturbation mechanisms, can confer activity against Gram-positive and Gram-negative pathogens.
On May 15, 2024, Recce reported that it had successfully dosed the first male and female participants in the nexCohortrt with RECCE® 327, 4,000mg intravenously, at a fast infusion rate of 20 minutes in its Phase I/II UTI/Urosepsis clinical trial. On June 28, 2024, Recce announced that the Phase I/II rapid infusion clinical trial demonstrated efficacy in bacterial growth in dosed participants injected with RECCE® 327 at the highest tested dose of 4,000mg. These results indicate that RECCE® 327 administered intravenously is safe and efficacious against E. coli.
On October 8, 2024, the company announced that RECCE® 327 topical gel (R327G) was safe and well tolerated in human subjects, with promising antibacterial responses observed in patients.
Recce Pharmaceuticals Ltd (ASX: RCE, FSE: R9Q) is developing a New Class of Synthetic Anti-Infectives designed to address the urgent global health problems of antibiotic-resistant superbugs and emerging viral pathogens. On June 18, 2024, the Company confirmed a further cash refund of AUD $2,624,860.47 for the Research and Development Tax Incentive rebate from the Australian Tax Office for the financial year ending 30 June 2023. On August 5, 2024, the Company's pro forma cash position was A$19.8 million.
RECCE® 327 Urinary Tract Infection (UTI) Treatment Dosage
RECCE® 327 may be administered for intravenous, topical, nasal, oral, and inhaled use. RECCE® 327's universal mechanism of action has a patented ability to continuously kill bacteria without a tendency for the emergence of resistance, even with repeated use, indicating a unique ability to combat antibiotic-resistant superbugs. The Company has explored multiple infusion times of R327: 15 minutes, 20 minutes, 30 minutes, and 45 minutes. The highest dose tested in the phase 1 study is 4,000mg. Administering antibiotics through rapid intravenous infusions has proven to be a safe and effective method that significantly impacts patient treatment, reduces wait times, and alleviates nursing workloads worldwide.
RECCE® 327 Urinary Tract Infection (UTI) Indication
Data in 2024 is expected to pave the way for a Phase II UTI/Urosepsis efficacy trial, potentially establishing R327 as a frontline treatment. UTI is one of the most common infectious diseases in the pediatric population. In high-income countries, UTIs affect up to 2.8% of children annually, with recurrence rates ranging from 8% to 30% [2,3]. It is estimated that 11.3% of females and 3.6% of males develop at least one episode of UTI within the first 16 years of life.
RECCE® 327 Acinetobacter Baumannii Indication
On July 8, 2024, results from a study on the efficacy of RECCE® 327 (R327) against the multidrug-resistant World Health Organization (WHO) priority pathogen Acinetobacter baumannii (A. baumannii) demonstrated R327’s bactericidal activity compared to placebo and ciprofloxacin in just one-hour post-treatment and at 24 hours post-treatment in primary human epidermal keratinocytes (skin cells) infected with A. baumannii.
RECCE® 327 Mechanism of Action
Most antibiotics inhibit a single target, such as bacterial gyrase enzymes, cell wall biosynthetic enzymes, or enzymes required for DNA replication during bacterial cell division. They operate on a ‘lock and key’ mechanism and only bind to a few active sites on the bacterial target. However, if a mutation is introduced into the target site, the antibiotic will cease to be effective. Recce’s anti-infectives are wholly synthetic, based on a patented polymeric structure, and have been designed to overcome resistance.
RECCE 327 UTI Treatment Side Effects
No significant side effects have been reported. In April 2024, Recce Pharmaceuticals reported that an Independent Safety Committee had approved an increase of R327 to 4,000mg (I.V.) over a fast infusion of 30 minutes. In June 2024, the Company reported no serious side effects in a Phase 1/2 study.
RECCE 327 UTI Treatment Availability
RECCE® 327 is not market-approved for human use. As of April 2024, the Company was producing 5,000 GMP doses of R327 per week.
RECCE 327 UTI Treatment News
August 5, 2024—Recce Pharmaceuticals Limited announces the successful close of its Share Purchase Plan, which was announced on July 2, 2024.
June 28, 2024 - Dr. Marc Sharp, Chief Scientific Officer at Linnaeus Bioscience, leading independent experts in bacterial Mechanism of Action analysis, added: "The ability of R327 to achieve biologically relevant concentrations and exhibit antibacterial activity in urine samples is highly encouraging."
June 18, 2024 - Recce Pharmaceuticals CEO James Graham said, "We are pleased that R327 has been included in the list of antibacterial products to tackle the urgent global health threat posed by antibiotic resistance. There is a demand for new antibiotic therapies, and this report further showcases R327's potential as a novel treatment for a broad range of life-threatening and resistant bacteria."
May 15, 2024 - The first participants were successfully dosed at 4,000mg IV over 20 minutes, at 4,000mg in a phase 1/2 study.
April 17, 2024 - Recce Pharmaceuticals Ltd. announced the successful batch completion under Good Manufacturing Practices for RECCE® 327 (R327), with the patented manufacturing process now producing 5,000 GMP doses of R327 per week.
September 26, 2023 - Recce Pharmaceuticals Ltd. announced it completed the cohort dosing of healthy male and female subjects in its Phase I/II clinical trial, evaluating its lead anti-infective candidate, RECCE® 327, at faster infusion rates.
RECCE® 327 UTI Treatment Clinical Trials
UTI clinical trials are active as of May 2024. A phase 1 clinical trial (ACTRN12623000448640) consists of up to 4 cohorts with 4 participants at each dose level. Each participant will begin with a single dose of RECCE®327 intravenously over Period A (longer infusion duration), followed by 48 hours of safety surveillance and PK data collection. The second dose of RECCE®327 infusion over Period B (shorter infusion duration) had the same dose level and concentration and a minimum time elapsed of 48 hours from the start of the first to the second dose. For the subsequent, a non-Data Safety Monitoring Board committee will review the safety and PK data (the latter, if available). It may suggest adjusting the dose level, infusion rate, and/ or concentration of the RECCE®327 before proceeding to the nexCohortrt. The non-DSMB committee may determine not to proceed with additional cohorts as well. Four non-DSMB committee meetings will be planned one week after Period B for the last participant in eacCohortrt.
Announced on June 28, 2024, the Phase 1/2 trial met all primary endpoints, demonstrating the compound's tolerability and strong antibacterial efficacy. The study successfully concludes having determined an optimal dosing regimen for R327 (20-minute infusion optimal) intravenously, showing rapid onset and sustained impact on Escherichia coli via an ATP mechanism in the urine of dosed participants with the safety of participants maintained. Building on these promising results, Recce Pharmaceuticals plans to commence a Phase 2 trial in the second half of 2024, involving 30 patients, to validate these findings further and explore additional therapeutic indications for 327. The Company is also investigating the potential of R327 in treating a broader range of bacterial infections beyond UTIs and urosepsis, such as acute bacterial skin and skin structure infections.