Recce Pharmaceuticals Achieves Positive Phase I Clinical Trial Data of RECCE® 327 as an Intravenous Infusion Formulation

Highlights:

• Independent examiners confirm Phase I study of RECCE^® 327 (R327) in 80 human subjects across eight cohorts achieved all primary study endpoints, met international regulatory standards, and demonstrated R327 to be safe and well-tolerated
• Dosing was achieved in accordance with efficacy demonstrated in Gram-positive and Gram-negative animal infection models
• Phase I/II ‘fast infusion’ dosing of R327 as an intravenous (IV) formulation is tracking towards primary study endpoints, with expected data read-outs in H2 2023

SYDNEY Australia, July 20, 2023 (GLOBE NEWSWIRE) — Recce Pharmaceuticals Ltd (ASX: RCE, FSE: R9Q) (the Company), the Company developing a new class of synthetic anti-infectives, today announced positive results from a Phase I (R327-001) study of RECCE^® 327 (R327) as an intravenous (IV) infusion formulation in 80 healthy male subjects.

“We are pleased to see that even when administered at doses much higher than the expected therapeutic window, R327 IV does not lead to safety or toxicity issues in healthy subjects,” said Alan W Dunton, MD, Non-Executive Director of Recce Pharmaceuticals and Medical Monitor of the Phase I trial. “We believe in the potential of R327 to provide a much-needed solution to patients with serious infections and look forward to providing interim proof-of-efficacy data in pre-sepsis patients in H2 2023.”

John Prendergast, Ph.D., Executive Chairman of Recce Pharmaceuticals, added, “We are highly encouraged by the safety and tolerability R327 demonstrated across eight cohorts at doses up to 6,000 mg, which is above the expected therapeutic range. We look forward to building off these results by initiating a Phase II study in patients with early-stage sepsis. There are currently no specific treatment options available for those with sepsis, with patients generally given broad-spectrum antimicrobials at first and then refined once the antibiograms become available a few hours after treatment initiations, which can be critical. Our next-generation anti-infectives have the potential to change the treatment landscape by becoming a universal first-line treatment for patients with life-threatening infections from both Gram-positive and Gram-negative bacteria, including their superbug forms.”

The Phase I ascending-dose,¹ randomized, placebo-controlled, parallel, double-blind, single-dose, first-in-human study evaluated the safety and pharmacokinetics (PK) of R327 in healthy male subjects. A total of 80 subjects were randomized in eight single-dose cohorts, and 60 subjects received R327, with 20 receiving placebo. Enrolled subjects completed dosing per the protocol and completed the trial without dosing interruptions.

In concurrence with the Therapeutic Goods Administration clinical trial regulatory procedures, the recruitment for the study is closed and marked ‘Complete’ with no ‘Serious Adverse Events’ reported.

Summary of Results

• No serious adverse events (SAEs) or deaths were reported.
• No clinically significant changes were noted in any hematology parameter(s) in any cohort.
• No clinically significant changes were noted in any chemistry parameter(s) in any cohort, with kidney and liver functions all normal.
• All coagulation parameters remained within normal limits or were deemed not clinically significant, and normal blood clotting properties were maintained.
• No clinically significant changes were noted in any urinalysis parameter(s) in any cohort.
• No clinically significant changes were noted in any vital signs, including systolic blood pressure, diastolic blood pressure, heart rate, respiratory rate, and body temperature in any cohort.
• No clinically significant changes were noted in 12-lead electrocardiogram (ECG) parameter(s), including cardiac events in any subject across all cohorts.
• No clinically significant changes were noted in cardiac telemetry parameter(s) in any subject across all cohorts, with no cardiac abnormalities during continuous heart monitoring.

Safety and Tolerability Results
R327 was found to be well-tolerated with a good safety profile across all dose groups from 50 mg to 6,000 mg when administrated over a one-hour IV infusion, referred to in the table titled “Adverse Events (TEAEs).” All treatment-emergent adverse events (TEAEs) across the cohorts, including placebo groups, were classified as mild or moderate. All outcomes for the TEAEs were recovered or resolved.

Figure 1 is available at https://www.globenewswire.com/NewsRoom/AttachmentNg/574cc755-b86d-4e44-86be-adb977065e95

Pharmacokinetic Results – Potential for R327 to be Used to Treat Sepsis
The results showed a significant dose-dependent concentration of R327 in both the urine and the plasma, highlighting the potential of R327 as a treatment for sepsis and complicated/uncomplicated urinary tract infections (UTIs).

As shown in the graph titled “Concentration of R327; Human Plasma,” there was a significant dose-dependent concentration of R327 in the subjects’ plasma. The results demonstrate a consistent and proportional linear increase across measured doses of R327. R327 displayed a compelling profile for a sepsis drug candidate, with no observed commensurate spike in drug concentration, possibly leading to better-to-control side effects.

Figure 2 is available at https://www.globenewswire.com/NewsRoom/AttachmentNg/2886b443-14f2-410c-8053-e56b3ac537e4

Additional Positive Findings:

Potential for R327 to be Used to Treat UTIs:
UTIs are responsible for about 30% of all sepsis infections, defined as ‘urosepsis’ R327’s potential as a treatment option across the spectrum of infectious diseases strengthens its position in this area of unmet medical need.

As shown in the table titled “Ratio of R327 in Urine and Plasma,” the clinical results demonstrated a significant dose-dependent concentration of R327 in both the urine and the plasma, with up to twenty-one-fold higher concentration in the urine. It was also found that the primary route of excretion of R327 appeared to be through the kidney into the ureters and down into the bladder.

Figure 3 is available at https://www.globenewswire.com/NewsRoom/AttachmentNg/8f378da3-56a3-4ae5-bd72-949ffbc4afa3

Figure 4 is available at https://www.globenewswire.com/NewsRoom/AttachmentNg/c56a41db-2dd3-4f7f-9503-4c48924144bc

Furthermore, an independent study demonstrated that R327 in the presence of human urine could reduce the number of viable Escherichia coli (E. coli) bacteria by over 99.99% in a matter of minutes, as shown in the graph titled “RECCE^® 327 Kills Quickly in Urine.” This, along with the excellent safety profile of R327 and preclinical in vivo kidney and UTI bacterial infections studies, highlights the great potential of R327 in treating complicated and uncomplicated UTIs.

Figure 5 is available at https://www.globenewswire.com/NewsRoom/AttachmentNg/e603cdbb-967f-4ecc-8fbb-644a50fcff3f

Healthy cell viability remained exceptionally high, even improving in the presence of R327

Figure 6 is available at https://www.globenewswire.com/NewsRoom/AttachmentNg/33fd0c96-f8eb-4768-a2c2-4a555356a777

Another positive finding was the improvement of healthy human cells in the PK/pharmacodynamic (PD) analysis, including indications of improved kidney health from R327 as it was excreted from the body.

The graph titled “Viability of a Monocyte Cell Line Treated with R327, PEG 200 and Acrolein” represents an independent study of the effect of R327 on healthy human cells, indicating cell health improving >100% since repeated across multiple independent confirmatory investigations. In an unwell patient treatment setting, the wider support of human health is likely a welcomed feature of dosing R327.

Figure 7 is available at https://www.globenewswire.com/NewsRoom/AttachmentNg/797ee3ef-6591-424e-89f9-e7d75f478688

The graph titled “Viability of Healthy Kidney Cells Treated with R327, PEG 200 and Acrolein” further demonstrates the safety of R327 on the viability of mammalian cells and the effect of R327 on a kidney cell line (ATCC CRL 1573). Results show that R327 was well-tolerated across a wide concentration range without any evident cytotoxicity to the kidney cells.

In most cases, antibiotics can cause kidney damage and can be quite a common occurrence. For example, in hospital wards, antibiotics account for approximately 10% of episodes of acute renal failure and 60% of drug-related kidney damage.² Moreover, antibiotics can form crystals that don’t break down and block urine flow.³ One such example is one of the world’s most widely prescribed commercial antibiotics (generates over US $10bn in revenue), which is known to cause urine crystallization.⁴ Others have substances that can damage certain kidney cells when attempting to filter them out. As previously mentioned, the results of the Phase I trial demonstrated no change in any chemistry parameter(s) to those dosed with R327, with all kidney and liver functions appearing to be normal.

Next Steps
The successful Phase I safety and tolerability study of R327 IV in healthy male volunteers has paved the way for the next stage of R327’s clinical development in sepsis and UTIs. The Company is currently conducting a Phase I/II UTI clinical trial evaluating R327 IV at faster infusion rates – recently announcing its first cohort dosed, including its first female subject.

About Recce Pharmaceuticals Ltd
Recce Pharmaceuticals Ltd (ASX: RCE, FSE: R9Q) is developing New Classes of Synthetic Anti-Infectives designed to address the urgent global health problems of antibiotic-resistant superbugs and emerging viral pathogens.

Recce’s anti-infective pipeline includes three patented, broad-spectrum, synthetic polymer anti-infectives: RECCE^® 327 as an intravenous and topical therapy that is being developed for the treatment of serious and potentially life-threatening infections due to Gram-positive and Gram-negative bacteria including their superbug forms; RECCE^® 435 as an orally administered therapy for bacterial infections; and RECCE^® 529 for viral infections. Through their multi-layered mechanisms of action, Recce’s anti-infectives have the potential to overcome the hypercellular mutation of bacteria and viruses – the challenge of all existing antibiotics to date.

The FDA has awarded RECCE^® 327 Qualified Infectious Disease Product designation under the Generating Antibiotic Initiatives Now (GAIN) Act – labelling it for Fast Track Designation, plus 10 years of market exclusivity post approval. Further to this designation, RECCE^® 327 has been included on The Pew Charitable Trusts Global New Antibiotics in Development Pipeline as the world’s only synthetic polymer and sepsis drug candidate in development. RECCE^® 327 is not yet market approved for use in humans with further clinical testing required to fully evaluate safety and efficacy.

Recce wholly owns its automated manufacturing, which is supporting present clinical trials. Recce’s anti-infective pipeline seeks to exploit the unique capabilities of its technologies targeting synergistic, unmet medical needs.

Corporate Contact
James Graham
Recce Pharmaceuticals Ltd
+61 (02) 9256 2571
[email protected] 

Media & Investor Relations (AU)
Andrew Geddes
CityPR
+61 (02) 9267 4511
[email protected] 

Media (USA)
Jordyn Temperato
LifeSci Communications
[email protected] 

Investor Relations (USA & EU)
Guillame van Renterghem
LifeSci Advisors
[email protected] 

¹ A single dose of R327 IV was infused in each cohort of healthy male subjects to demonstrate its safety before increasing the dose to another cohort of healthy male subjects.
²https://pubmed.ncbi.nlm.nih.gov/23059939/
³https://www.webmd.com/a-to-z-guides/medicine-hurt-kidneys#:~:text=way%20they%20should.-,Antibiotics,try%20to%20filter%20them%20out.
⁴https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8919213/#:~:text=Amoxicillin%20is%20known%20to%20cause,hematuria%20or%20acute%20renal%20failure.