Cefepime-Taniborbactam Superior to Meropenem for the Composite Efficacy Endpoint

Composite Efficacy Sustained at Late Follow-up Visit

Safety Profile Consistent with Meropenem

Malvern, PA, Parsippany, NJ, and Florence, Italy – February 20, 2024 – Venatorx Pharmaceuticals, Melinta Therapeutics LLC (“Melinta”), and Menarini Group today announced that The New England Journal of Medicine (NEJM) published the results of the CERTAIN-1 Phase 3 clinical study of the investigational agent cefepime-taniborbactam for the treatment of adult patients with complicated urinary tract infections (cUTI) and acute pyelonephritis (AP), including those with bacteremia. The results showed that cefepime-taniborbactam was superior to meropenem for the treatment of complicated UTI that included acute pyelonephritis, with a similar safety profile to meropenem.

“Gram-negative infections such as cUTI have become increasingly difficult to treat due to acquired bacterial resistance to multiple classes of antibiotics. Cefepime-taniborbactam has the potential to treat a broad range of patients with cUTI due to suspected or confirmed multidrug-resistant (MDR) pathogens including Enterobacterales and Pseudomonas aeruginosa,” said Paul C. McGovern, MD, Senior Vice President at Venatorx and co-author of the publication. “This Phase 3 study is the culmination of a long journey of discovery and development, and we look forward to progressing this agent through the next regulatory stages so that the drug may reach patients world-wide as expeditiously as possible.”

Christine Ann Miller, President and Chief Executive Officer of Melinta Therapeutics added, “We are pleased to see these results published in the New England Journal of Medicine. We look forward to leveraging our experience in marketing infectious disease products and our established commercial infrastructure, especially within the hospital and acute care settings, to make cefepime-taniborbactam available to physicians and their patients with complicated urinary tract infections if approved.

“E.coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa are largely involved in cUTI Gram-negative pathogens infections reaching nearly 75% in Europe. We believe that the NEJM published CERTAIN-1 Phase 3 data indicating cefepime- taniborbactam’s superiority on the composite endpoint of microbiological and clinical response alongside its comparable safety profile versus meropenem provides useful insight as to its expected contribution, upon approval by relevant regulatory authorities, in the treatment of hospitalized patients with cUTI starting in Europe” said Najy Alsayed, Global Therapeutic Area Head-Infectious Diseases at Menarini Group.

About CERTAIN-1
CERTAIN-1 was a randomized, multicenter, double-blind, active-controlled, non-inferiority study of hospitalized patients (N=661) with complicated urinary tract infections (cUTI), including acute pyelonephritis (AP), comparing cefepime-taniborbactam (2.5 g every 8 hours) to meropenem (1 g every 8 hours). The primary endpoint was the composite microbiologic and clinical response at the Test of Cure (TOC) visit (Day 19-23) in the microbiological intention-to-treat (microITT) population. The non-inferiority margin was -15% and there was a prespecified superiority analysis if non-inferiority was concluded.

Efficacy Data
Cefepime-taniborbactam met the prospectively defined non-inferiority primary endpoint of composite microbiologic and clinical response versus meropenem at the TOC visit (70.6% response rate for cefepime-taniborbactam versus 58.0% for meropenem). The prespecified superiority analysis at the TOC visit demonstrated that cefepime-taniborbactam was statistically superior to meropenem for the composite endpoint (response rate difference: 12.6% [95% confidence interval (CI): 3.1, 22.2]; p=0.009) and for the microbiologic endpoint (response rate difference: 11.7% [CI: 2.9, 21.0]); the clinical endpoint response rate difference was 4.5% [CI: -2.6, 12.6]. At the Late Follow-up (LFU) visit (Day 28-35), cefepime-taniborbactam demonstrated sustained statistical superiority to meropenem for the composite endpoint (63.8% response rate for cefepime-taniborbactam versus 51.7% for meropenem (response rate difference: 12.1% [CI: 2.2, 21.9]) and for the clinical response endpoint (response rate difference: 9.9% [CI: 1.5, 18.8); the microbiologic endpoint response rate difference was 7.7% [CI: -1.6, 17.3]. Additionally, cefepime-taniborbactam maintained a numerical advantage to meropenem against resistant pathogens: cefepime-resistant (71% response rate for cefepime-taniborbactam versus 53% for meropenem), ESBL-producing (71% response rate for cefepime-taniborbactam versus 55% for meropenem) and MDR (68% response rate for cefepime-taniborbactam versus 60% for meropenem).

Safety Data
Cefepime-taniborbactam demonstrated a safety profile consistent with meropenem. Treatment-emergent adverse events occurred in 35.5% and 29.0% of cefepime-taniborbactam and meropenem treated patients respectively. Serious adverse events occurred in 2.0% of cefepime-taniborbactam patients and 1.8% of meropenem treated patients. The most frequently reported treatment-emergent adverse events were headache (6.1% with cefepime-taniborbactam versus 3.7% for meropenem), diarrhea (4.1% versus 2.3%), and constipation (3.2% versus 1.4%). Three percent of patients treated with cefepime-taniborbactam discontinued therapy due to a treatment-emergent adverse event versus 0.9% of patients treated with meropenem. The safety data for cefepime-taniborbactam was consistent with the historical safety data for cefepime.

About Cefepime-Taniborbactam
Cefepime-taniborbactam is an investigational agent that is a combination of cefepime, a fourth-generation cephalosporin, and the novel beta-lactamase inhibitor (BLI), taniborbactam, that exhibits broad coverage of both serine- and metallo-beta-lactamases. In combination with cefepime, taniborbactam is under development as a new treatment option for patients with serious bacterial infections caused by difficult-to-treat drug resistant gram-negative pathogens, including carbapenem-resistant Enterobacterales (CRE) and carbapenem-resistant or multidrug-resistant Pseudomonas aeruginosa (CRPA/MDR-PA).

Funding Partners and Collaborators for Cefepime-Taniborbactam
This project has been funded in part with federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under contract number HHSN272201300019C, and Wellcome Trust under Award No. 360G-Wellcome-101999/Z/13/Z, and has continued with federal funds from the Department of Health and Human Services; Administration for Strategic Preparedness and Response, Biomedical Advanced Research and Development Authority, under contract numbers HHSO100201900007C and 75A50122C00080.

In September 2018, Venatorx entered into an exclusive license agreement with Everest Medicines to support the development, registration, and commercialization of cefepime-taniborbactam in Greater China, South Korea, and select countries in Southeast Asia. Everest will be solely responsible for the commercialization of cefepime-taniborbactam in its territory and Venatorx will be eligible to receive royalties on net sales.

In April 2020, Venatorx and the GARDP Foundation (GARDP) announced a collaboration to accelerate the development of, and access to, cefepime-taniborbactam for adult and pediatric populations. Venatorx has granted GARDP exclusive rights to distribute and sub-distribute cefepime-taniborbactam, once it is approved for clinical use, in low- and lower-middle-income countries.

In November 2023, Venatorx and Melinta entered into an exclusive License Agreement to facilitate a strategic partnership in the U.S. to commercialize cefepime-taniborbactam, a beta-lactam / beta-lactamase inhibitor (BL/BLI) combination antibiotic being developed for the treatment of complicated urinary tract infections (cUTI) and hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP) in adults.

In December 2023, Venatorx entered into an agreement with Menarini Group, who acquired the exclusive rights to commercialize, upon approval of relevant health authorities, cefepime-taniborbactam in 96 countries in Europe, Latin America, Middle East, Turkey and North Africa and the Commonwealth of Independent States (CIS).

About Venatorx Pharmaceuticals
Venatorx is a private, late-stage clinical pharmaceutical company focused on improving health outcomes for patients with multidrug-resistant bacterial infections and hard-to-treat viral infections. Venatorx’s lead program, cefepime-taniborbactam, is a clinical-stage antibiotic that completed a Phase 3 study in adults with complicated urinary tract infections (cUTI), including pyelonephritis. In October 2022, BARDA awarded a contract of up to $318M for development and procurement of cefepime-taniborbactam for the treatment of melioidosis and multi-drug resistant infections. Cefepime-taniborbactam is currently under review by the FDA for the treatment of cUTI, including acute pyelonephritis. Venatorx is also developing an oral antibacterial, ceftibuten-ledaborbactam (formerly known as VNRX-7145), for the treatment of cUTI, including pyelonephritis, caused by certain bacteria in adult patients with limited treatment options; this product is completing Phase 1 and will advance directly to a global Phase 3 cUTI clinical trial.. For more information about Venatorx and its anti-infectives portfolio, please visit www.venatorx.com.

About Melinta Therapeutics LLC
Melinta Therapeutics is a biopharmaceutical company dedicated to providing innovative therapies to people impacted by acute and life-threatening illnesses. We focus our expanding portfolio on serving patients with an unmet need because that’s how we make the most meaningful impact. At Melinta, we’re visionaries dedicated to innovation while staying grounded in what matters most: patients. Our portfolio currently includes seven commercial-stage products: BAXDELA® (delafloxacin), KIMYRSA® (oritavancin), MINOCIN® (minocycline) for Injection, ORBACTIV^® (oritavancin), REZZAYO^® (rezafungin for injection), TOPROL-XL^® (metoprolol succinate) and VABOMERE^® (meropenem and vaborbactam). For more information about Melinta Therapeutics, our commitment to patients, and to learn about our portfolio of therapies, visit www.melinta.com.

About Menarini Group
The Menarini Group is a leading international pharmaceutical and diagnostics company, with a turnover of over $4.4 billion and over 17,000 employees. Menarini is focused on therapeutic areas with high unmet needs with products for cardiology, oncology, pneumology, gastroenterology, infectious diseases, diabetology, inflammation, and analgesia. With 18 production sites and 9 Research and Development centers, Menarini’s products are available in 140 countries worldwide. For further information, please visit www.menarini.com.

VENATORX MEDIA CONTACT:
Jennifer Guinan
Sage Strategic Marketing
jennifer@sagestrat.com
610.410.8111

MELINTA MEDIA RELATIONS CONTACT:
Sharon Dilling
sdilling@melinta.com
info@melinta.com

MENARINI GROUP PRESS OFFICE:
Valeria Speroni Cardi
pressoffice@menarini.it

Publication reaffirms the proven efficacy and safety of rezafungin dosed once-weekly versus a current standard of care echinocandin dosed once-daily

PARSIPPANY, NJ, and SAN DIEGO, CA — Dec 5, 2023 — Melinta Therapeutics, LLC and Cidara Therapeutics, Inc. (NASDAQ: CDTX) today announced the peer-reviewed publication of pooled data from two completed global clinical trials evaluating REZZAYO^® (rezafungin for injection) for the treatment of candidemia and invasive candidiasis. The article, “Efficacy and safety of rezafungin and caspofungin in candidemia and invasive candidiasis: pooled data from two prospective randomised controlled trials,” published in The Lancet Infectious Diseases, reports on pooled data analyses of the pivotal ReSTORE Phase 3 randomized controlled clinical trial, which demonstrated the non-inferiority of REZZAYO as compared to caspofungin for all-cause mortality, and the STRIVE Phase 2 randomized controlled trial, which provided safety and supportive efficacy data for REZZAYO. The pooled analyses in the article further support the non-inferiority of rezafungin versus caspofungin for all-cause mortality and with similar safety profiles and provide additional evidence for potential early treatment benefits. 

Christine Ann Miller, president and chief executive officer of Melinta Therapeutics, said, “We are very pleased with the publication of the pooled data from two completed clinical trials, the ReSTORE Phase 3 trial and the Phase 2 STRIVE trial, in Lancet ID, which, combined, continue to demonstrate a consistent efficacy and safety profile of REZZAYO as compared to caspofungin. These findings are of clinical importance given the ongoing morbidity and mortality caused by candidemia and invasive candidiasis. Since the approval of REZZAYO, Melinta has been leveraging our commercial infrastructure and experience in marketing infectious disease products, particularly within the hospital and acute care settings, to make REZZAYO available to healthcare providers and their patients suffering with candidemia and invasive candidiasis.”

Taylor Sandison, MD, MPH, chief medical officer at Cidara Therapeutics, added, “The continued clinical success of REZZAYO across global populations reinforces its potential as a therapeutic option for patients suffering from candidemia and invasive candidiasis.”

The ReSTORE pivotal Phase 3 trial demonstrated that REZZAYO met the primary endpoint for the U.S. Food and Drug Administration (FDA) New Drug Application (NDA) submission of all-cause mortality at Day 30, and also met the primary endpoint for the European Medicines Agency (EMA) Marketing Authorization Application (MAA) submission of global cure at Day 14. The STRIVE Phase 2 study provided safety and supportive efficacy data on REZZAYO.

In both studies, researchers evaluated one 400 milligram (mg) dose of REZZAYO for the first week followed by 200 mg of REZZAYO dosed once weekly for up to four weeks in total. REZZAYO was generally well tolerated and had a similar safety profile to caspofungin.

On March 22, 2023, the FDA approved REZZAYO for the treatment of candidemia and invasive candidiasis in adults with limited or no alternative treatment options. REZZAYO is the first new treatment option approved for patients with candidemia and invasive candidiasis in over fifteen years. Based on Qualified Infectious Disease Product (QIDP) designation, REZZAYO was approved under Priority Review. The Centers for Medicare & Medicaid Services (CMS) issued a permanent product-specific J-Code (J0349, Injection, rezafungin, 1 mg) for REZZAYO injection effective October 1, 2023. CMS also granted a new technology add-on payment (NTAP) for REZZAYO for eligible participating hospitals when Medicare patients are treated in the inpatient acute care hospital setting.

Last year, Melinta announced that it had acquired the exclusive rights to commercialize rezafungin in the U.S. from Cidara. Cidara retains the rights to rezafungin in Japan and has licensed the commercial rights to Melinta Therapeutics in the U.S. and Mundipharma in all other geographies. The EMA accepted the MAA for rezafungin in August 2022, and it is currently under review.  In October, the EMA Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion for rezafungin (rezafungin acetate) for the treatment of invasive candidiasis in adults.

About REZZAYO^® (rezafungin for injection)

REZZAYO (rezafungin for injection) is a novel once weekly echinocandin approved in the United States for the treatment of candidemia and invasive candidiasis in adults. REZZAYO is currently being studied for the prevention of invasive fungal diseases in adults undergoing allogeneic blood and marrow transplantation. The structure and properties of REZZAYO are specifically designed to improve upon a clinically validated mechanism.

INDICATIONS AND USE

REZZAYO is an echinocandin antifungal indicated in patients 18 years of age or older who have limited or no alternative options for the treatment of candidemia and invasive candidiasis. Approval of this indication is based on limited clinical safety and efficacy data.

REZZAYO has not been studied in patients with endocarditis, osteomyelitis, and meningitis due to Candida.

IMPORTANT SAFETY INFORMATION

REZZAYO is contraindicated in patients with known hypersensitivity to rezafungin or other echinocandins.

REZZAYO may cause infusion-related reactions, including flushing, sensation of warmth, urticaria, nausea, or chest tightness. If these reactions occur, slow or pause the infusion.

REZZAYO may cause photosensitivity. Advise patients to use protection from sun exposure and other sources of UV radiation.

Abnormalities in liver tests have been seen in clinical trial patients treated with REZZAYO. Monitor patients who develop abnormal liver tests and evaluate patients for their risk/benefit of continuing REZZAYO therapy.

Most common adverse reactions (incidence ≥ 5%) are hypokalemia, pyrexia, diarrhea, anemia, vomiting, nausea, hypomagnesemia, abdominal pain, constipation, and hypophosphatemia.

Please see the full Prescribing Information for REZZAYO (rezafungin for injection), available at www.rezzayo.com.

About Melinta Therapeutics LLC
Melinta Therapeutics is a biopharmaceutical company dedicated to providing innovative therapies to people impacted by acute and life-threatening illnesses. We focus our expanding portfolio on serving patients with an unmet need because that’s how we make the most meaningful impact. At Melinta, we’re visionaries dedicated to innovation while staying grounded in what matters most: patients. Our portfolio currently includes seven commercial-stage products: BAXDELA® (delafloxacin), KIMYRSA® (oritavancin), MINOCIN® (minocycline) for Injection, ORBACTIV® (oritavancin), REZZAYO® (rezafungin for injection), TOPROL-XL® (metoprolol succinate) and VABOMERE® (meropenem and vaborbactam). For more information about Melinta Therapeutics, our commitment to patients, and to learn about our portfolio of therapies, visit www.melinta.com.

About Cidara Therapeutics

Cidara Therapeutics is using its proprietary Cloudbreak® platform to develop novel drug-Fc conjugates (DFCs). These targeted immunotherapies offer the unique opportunity to create “single molecule cocktails” comprised of targeted small molecules and peptides coupled to a human antibody fragment (Fc). DFCs are designed to save lives and improve the standard of care for patients facing cancers and other serious diseases by inhibiting specific disease targets while simultaneously engaging the immune system. In addition, Cidara received FDA approval for REZZAYO® (rezafungin for injection), which it has licensed to multiple partners to commercialize in the U.S. and ex-U.S. 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,” “believe,” “could,” “expect,” “may,” “plan” or “will”. Forward-looking statements in this release include, but are not limited to, statements related to REZZAYO™ will be included in institutional formularies, prescribed by physicians or reimbursed by payors. . 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. These and other risks are identified under the caption “Risk Factors” in Cidara’s Annual Report on Form 10-K for the fiscal year ended December 31, 2022, and other filings subsequently made with the Securities and Exchange Commission. 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.

MELINTA MEDIA RELATIONS CONTACT:
Sharon Dilling
sdilling@melinta.com

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

CIDARA MEDIA RELATIONS CONTACT:
Veronica Eames
LifeSci Communications
(646) 970-4682
veames@lifescicomms.com

Parsippany, N.J., and Malvern, PA — November 9, 2023 — Melinta Therapeutics LLC (“Melinta”) and Venatorx Pharmaceuticals, Inc. (“Venatorx”), today announced that they have entered into a License Agreement to facilitate a strategic partnership in the U.S. to commercialize cefepime-taniborbactam, a beta-lactam / beta-lactamase inhibitor (BL/BLI) combination antibiotic being developed for the treatment of complicated urinary tract infections (cUTI) and hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP) in adults.

The partnership follows Venatorx’s submission of a New Drug Application (NDA) for cefepime-taniborbactam for the treatment of cUTI including pyelonephritis, in adults. Venatorx has been assigned a Prescription Drug User Fee Act (PDUFA) target action date for February 22, 2024. The U.S. Food and Drug Administration (FDA) granted cefepime-taniborbactam Qualified Infectious Disease Product (QIDP) and Fast Track designations for both the cUTI and HABP/VABP indications.

Cefepime-taniborbactam was developed to address the need for new, novel antibiotics to battle increasing gram-negative resistance, which is especially critical for high-risk patients. Due to its broad spectrum of in vitro activity against key, common pathogens with established and rapidly increasing mechanisms of carbapenem resistance, such as serine- and metallo-beta-lactamases, and the positive results demonstrated in the CERTAIN-1, cUTI study, cefepime-taniborbactam, if approved, will address a critical unmet need. CERTAIN-1 was a randomized, double-blind, active-controlled Phase 3 trial comparing cefepime-taniborbactam to meropenem in hospitalized adults with cUTI including acute pyelonephritis (AP). Cefepime-taniborbactam has also demonstrated in vitro activity against CDC Urgent and Serious Threat Pathogens multidrug-resistant Pseudomonas aeruginosa, carbapenem-resistant Enterobacterales, and Extended Spectrum Beta-lactamase-producing (ESBL) Enterobacterales.

“The addition of cefepime-taniborbactam accelerates our long-term growth strategy, and if approved, would expand and complement our existing portfolio, and provide clinicians with another option in the fight against the growing crisis of antimicrobial resistance,” said Christine Ann Miller, President and Chief Executive Officer, Melinta Therapeutics. “Importantly, this partnership supports Melinta’s mission of providing innovative therapies to people impacted by acute and life-threatening illnesses.” Miller added, “While building upon our demonstrated ability to commercialize products in the hospital market, our partnership will also provide a strong foundation for getting this important medicine into the hands of healthcare providers, and ultimately to patients across the U.S.”

“The progression of cefepime-taniborbactam from invention through clinical trials to FDA review is a source of enormous pride to the Venatorx team. With its U.S.  commercial infrastructure and significant experience in commercializing antibiotics, Melinta is ideally positioned to bring this agent to patients in the U.S.,” said Christopher J. Burns, Ph.D., Chief Executive Officer of Venatorx. “This partnership will allow Venatorx to continue advancing all of the R&D and Regulatory elements of its infectious diseases portfolio including its U.S. Government contractual commitments.”

Funding Partners and Collaborators for cefepime-taniborbactam

Development of cefepime-taniborbactam began with federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services under contract number HHSN272201300019C, and Wellcome Trust under award number 360G-Wellcome-101999/Z/13/Z, and continues with federal funds from the Biomedical Advanced Research and Development Authority, Administration for Strategic Preparedness and Response, Department of Health and Human Services under contract numbers HHSO100201900007C and 75A50122C00080.

In September 2018, Venatorx entered into an exclusive license agreement with Everest Medicines to support the development, registration, and commercialization of cefepime-taniborbactam in People’s Republic of China, Macau, Hong Kong, Taiwan, South Korea, and select countries in Southeast Asia (the “Territory”).

In April 2020, Venatorx and GARDP announced a collaboration to accelerate the development of, and access to, cefepime-taniborbactam for adult and pediatric populations. Venatorx has granted GARDP exclusive rights to distribute and sub-distribute cefepime-taniborbactam, once it is approved for clinical use, in low- and lower middle-income countries.

About Melinta Therapeutics LLC
Melinta Therapeutics is a biopharmaceutical company dedicated to providing innovative therapies to people impacted by acute and life-threatening illnesses. We focus our expanding portfolio on serving patients with an unmet need because that’s how we make the most meaningful impact. At Melinta, we’re visionaries dedicated to innovation while staying grounded in what matters most: patients. Our portfolio currently includes seven commercial-stage products: BAXDELA® (delafloxacin), KIMYRSA® (oritavancin), MINOCIN® (minocycline) for Injection, ORBACTIV® (oritavancin), REZZAYO® (rezafungin for injection), TOPROL-XL® (metoprolol succinate) and VABOMERE® (meropenem and vaborbactam). For more information about Melinta Therapeutics, our commitment to patients, and to learn about our portfolio of therapies, visit www.melinta.com.

About Venatorx Pharmaceuticals, Inc.
Venatorx is a private, pre-commercial pharmaceutical company focused on improving health outcomes for patients with difficult-to-treat drug resistant gram-negative bacterial infections and viral infections. Venatorx’s lead asset, cefepime-taniborbactam, is an investigational antibiotic that completed a Phase 3 study (NCT03840148) in adults with complicated urinary tract infections (cUTI), including pyelonephritis and is under FDA review with a PDUFA action date of February 22, 2024. In October 2022, BARDA awarded a contract of up to $318M to Venatorx for development and procurement of cefepime-taniborbactam for the treatment of melioidosis and multidrug-resistant infections. As part of its broader pipeline, Venatorx is also developing an oral antibacterial, ceftibuten-ledaborbactam etzadroxil, that will advance directly to a global Phase 3 cUTI clinical trial under a recently announced third BARDA contract.  For the license transaction cited herein, TD Cowen served as financial advisor to Venatorx. For more information about Venatorx and its anti-infectives portfolio, please visit www.venatorx.com.

About Cefepime-Taniborbactam
Cefepime-taniborbactam is an investigational intravenous (IV) beta-lactam/beta-lactamase inhibitor (BL/BLI) antibiotic combination being developed for the treatment of complicated urinary tract infections (cUTIs), including pyelonephritis, and hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP). Cefepime-taniborbactam was accepted for review by the U.S. FDA for cUTI, including pyelonephritis with a PDUFA date of February 22, 2024.

Cefepime, a fourth-generation cephalosporin, is a widely used beta-lactam (BL) antibiotic with more than two decades of proven safety and clinical utility against susceptible gram-negative and gram-positive bacteria. Taniborbactam is a beta-lactamase inhibitor (BLI) that, in combination with cefepime, is being studied as a potential treatment option for patients with serious bacterial infections caused by antibiotic resistant gram-negative bacteria, most notably Extended Spectrum Beta-lactamase (ESBL)-expressing Enterobacterales, carbapenem-resistant Enterobacterales (CRE), and multidrug-resistant (MDR) Pseudomonas aeruginosa (MDR-PA), which can include carbapenem-resistant P. aeruginosa (CRPA).

Cefepime-taniborbactam has been granted Qualified Infectious Disease Product (QIDP) and Fast Track designations by the U.S. Food and Drug Administration (FDA). Fast Track designation is designed to facilitate the development, and to expedite the review of drugs to treat serious conditions that do not have sufficient treatment options. QIDP designation provides certain incentives for the development of new antibiotics, including priority review, as well as a five-year regulatory exclusivity extension. QIDP was authorized under the Generating Antibiotic Incentives Now (GAIN) Act of 2012, as part of the FDA Safety and Innovation Act, to underscore the urgency in development of new antibiotics.

About Gram-Negative Infections and Antimicrobial Resistance (AMR)
In a recent report on AMR, the U.S. Centers for Disease Control and Prevention (CDC) reported rates of resistance have increased significantly in the U.S. among bacterial pathogens including those commonly causing cUTI, pyelonephritis, and bacteremia. The CDC also cited that there are more than 2.8 million AMR infections annually in the U.S., which are directly related to more than 35,000 deaths.^[1]

Between 2014 and 2019, an analysis of U.S. UTI patients determined that 4.4% of cases were carbapenem resistant (CR) and 24.5% of U.S. UTI patients were bacteremic with 1.7% of cases caused by a CR pathogen. Patients with CR infections had a significantly longer hospital length of stay (LOS), were less likely to be discharged home, had a higher readmission rate, and had greater LOS-associated charges than patients with carbapenem-susceptible infections. Additionally, patients with bacteremia (urosepsis) due to CR pathogens had a significantly higher rate of mortality than those with carbapenem susceptible pathogens.^[2]

Gram-negative bacteria have multiple AMR mechanisms that continue to adapt in response to increases in antibiotic usage. Carbapenems are broad-spectrum antibiotics that have been widely used to treat infections caused by multidrug-resistant gram-negative bacteria, including Enterobacterales. With the increased global use of carbapenems, CRE have emerged, which have limited treatment options and are associated with increased morbidity and mortality. Resistance to carbapenems among Enterobacterales is primarily achieved by production of carbapenemases, which are enzymes capable of hydrolyzing carbapenem antibiotics and most other beta-lactams and fall into two distinct families: serine beta-lactamases and metallo-beta-lactamases (MBLs). Klebsiella pneumoniae carbapenemase (KPC), a class-A serine beta-lactamase, is one of the most prevalent carbapenemases, and New Delhi MBL (NDM) and Verona Integron-encoded MBL (VIM) are common variants of MBLs identified in gram-negative infections due to Enterobacterales and P. aeruginosa. According to an IHMA surveillance study in 2018-2019 and a JMI U.S. Surveillance study from 2021, MBLs were the most commonly identified carbapenem resistance mechanism globally among Enterobacterales isolates, with ~16 to 18% of U.S. CRE isolates carrying MBLs.^[3,4]

While CRPA is also increasing in some geographies due to emergence of MBLs, MDR-PA, which may exhibit resistance to carbapenems, represents an increasing challenge for clinicians and their patients in the U.S. and globally due to the paucity of treatment options for this primarily hospital-associated pathogen. Especially outside the U.S., CRPA may carry carbapenemases including MBLs (i.e., VIM); however, non-carbapenemase resistance mechanisms (i.e., efflux pumps, porins) also contribute to the growing global resistance of MDR-PA and CRPA.^[5]

If AMR infections continue on this trajectory, it has been projected that an estimated 10 million people will die per year of resistant infections by 2050—a number that surpasses the projected annual number of deaths (8.2 million) caused by cancer—and the cumulative cost to the global economy could be as high as U.S. $100 trillion.^[6] In the U.S., estimates have reached as high as U.S. $20 billion in excess direct healthcare costs, with an additional U.S. $35 billion associated with lost productivity.^[7] By 2050, the world is at risk of losing up to 3.8% of its annual gross domestic product with an annual shortfall of up to U.S. $3.4 trillion by 2030, a figure on par with losses attributable to the 2008 global financial crisis.^[8]

The Infectious Disease Society of America (IDSA) maintains updated guidance on the Treatment of Antimicrobial Resistant Gram-Negative Infections online at https://www.idsociety.org/practice-guideline/amr-guidance/.^[9] For those patients who do not respond to current treatment, new antibiotic therapies are needed to combat AMR.

About Complicated Urinary Tract Infections
Complicated UTIs, which include pyelonephritis, are defined as urinary tract infections ascending from the bladder accompanied by local and systemic signs and symptoms, including fever, chills, malaise, flank pain, back pain, and/or costovertebral angle pain or tenderness, that usually occur in the presence of a functional or anatomical abnormality of the urinary tract or in the presence of catheterization. Bacteremia can arise secondary to infections like cUTI and can result in substantial morbidity and mortality. ^[1] Annually in U.S., it is estimated that more than 3 million cUTI patients will be diagnosed and require antibiotic therapy leading to over $6 billion in annualized 30-day costs.^[10]

MELINTA MEDIA RELATIONS CONTACT:
Sharon Dilling

sdilling@melinta.com
info@melinta.com

VENATORX MEDIA RELATIONS CONTACT:
Jennifer Guinan
Sage Strategic Marketing
jennifer@sagestrat.com
610.425.8659

References
^[1] Antibiotic Resistance Threats in the United States 2019, U.S. Department of Health and Human Services, Centers for Disease Control and Prevention.
^[2] Shields et al. Burden of illness in U.S. hospitals due to carbapenem-resistant gram-negative urinary tract infections in patients with or without bacteremia. BMC Infectious Diseases (2021) 21:572.
^[3] Estabrook et al. Epidemiology of Resistance Determinants Identified in Meropenem-Nonsusceptible Enterobacterales Collected as Part of a Global Surveillance Study, 2018 to 2019. Antimicrobial Agents and Chemotherapy; May 2023, Vol. 67, Issue 5
^[4] Castanheira et al. Increase in the Occurrence of Carbapenem-Resistant Enterobacterales in United States Hospitals from 2019 to 2021 and Activity of Novel Beta-Lactams/Beta-Lactamase Inhibitor Combinations Against these Isolates, 2022 ID Week Abstract #664. Open Forum Infectious Diseases, Volume 9, Issue Supplement_2, December 2022, ofac492.716
^[5] Jean S-S, Harnod D and Hsueh P-R (2022) Global Threat of Carbapenem Resistant Gram-Negative Bacteria. Front. Cell. Infect.Microbiol.12:823684. doi:10.3389/fcimb.2022.823684[6] O’Neill, J. ‘Tackling Drug-Resistant Infections Globally: Final Report and Recommendations’. Review on Antimicrobial Resistance. May 2016.
^[6] O’Neill, J. ‘Tackling Drug-Resistant Infections Globally: Final Report and Recommendations’. Review on Antimicrobial Resistance. May 2016.
^[7] Antibiotic Resistance Threats in the United States 2013, U.S. Department of Health and Human Services, Centers for Disease Control and Prevention.
^[8] World Bank. Final Report Drug Resistant Infections: A Threat to Our Economic Future. Mar 2017.
^[9] Infectious Disease Society of America maintains updated guidance on the Treatment of Antimicrobial Resistant Gram-Negative Infections posted online at https://www.idsociety.org/practice-guideline/amr-guidance/ accessed November 2023.
^[10] Carreno et al. Longitudinal, nationwide, cohort study to assess incidence, outcomes, and costs associated with complicated urinary tract infection. Open Forum Infectious Diseases. 8 October 2019

PARSIPPANY, N.J.–Melinta Therapeutics, LLC (Melinta), a commercial-stage company providing innovative therapies for acute and life-threatening illnesses, announced today, the presentation of nine scientific presentations with data from its current anti-infective portfolio at Infectious Disease Week (IDWeek) 2023, taking place October 11-15, 2023, in Boston, MA.  

IDWeek is the combined annual meeting of the Infectious Diseases Society of America (IDSA), the Society for Healthcare Epidemiology of America (SHEA), the HIV Medicine Association (HIVMA), the Pediatric Infectious Diseases Society (PIDS), and the Society of Infectious Diseases Pharmacists (SIDP).

Details of the presentations are provided below. The complete program of titles and abstracts can be accessed on the IDWeek 2023 website at www.idweek.org.

Melinta Portfolio Poster and Oral Presentations

About Melinta Therapeutics 

Melinta Therapeutics is a biopharmaceutical company dedicated to providing innovative therapies to people impacted by acute and life-threatening illnesses. We focus our expanding portfolio on serving patients with an unmet need because that’s how we make the most meaningful impact. At Melinta, we’re visionaries dedicated to innovation while staying grounded in what matters most: patients. Our portfolio currently includes seven commercial-stage products: BAXDELA® (delafloxacin), KIMYRSA® (oritavancin), MINOCIN® (minocycline) for Injection, ORBACTIV® (oritavancin), REZZAYO™ (rezafungin for injection), TOPROL-XL® (metoprolol succinate) and VABOMERE® (meropenem and vaborbactam). For more information about Melinta Therapeutics, our commitment to patients, and to learn about our portfolio of therapies, visit Melinta.com.  
 

Melinta Media Relations Contact: 
Sharon Dilling 
Sr. Director, Corporate Communications 
Melinta Therapeutics 
sdilling@melinta.com

REZZAYO receives product-specific J-Code and is granted NTAP

PARSIPPANY, N.J., October 2, 2023 – Melinta Therapeutics (Melinta), a commercial-stage company providing innovative therapies for acute and life-threatening illnesses, today announced expanded reimbursement and access for REZZAYO™ (rezafungin for injection). REZZAYO, the first new treatment option approved for adult patients with candidemia and invasive candidiasis in over a decade, has been commercially available in the U.S. since July. 

The Centers for Medicare & Medicaid Services (CMS) issued a permanent product-specific J-Code (J0349, Injection, rezafungin, 1 mg) for REZZAYO injection effective October 1, 2023. CMS also granted a new technology add-on payment (NTAP) for REZZAYO for eligible participating hospitals when Medicare patients are treated in the inpatient acute care hospital setting.

“We are very excited to share the news of the issuance of the J-Code and the NTAP for REZZAYO,” said Christine Ann Miller, Melinta President and CEO. “These two important milestones will help facilitate access to this innovative treatment option in both inpatient and outpatient settings. For Melinta, this is a significant step toward realizing our vision that all patients who need our therapies will receive them.”

A permanent J-Code plays a pivotal role in establishing reimbursement for medical products and services, offering a standardized way to identify the drug across various payers. The unique J-Code can be used for REZZAYO in all outpatient treatment settings. The NTAP, in turn, will provide eligible, participating hospitals with an incremental payment for REZZAYO in addition to the standard Medicare Severity Diagnostic Related Group (MS-DRG) reimbursement for inpatient Medicare cases beginning October 1, 2023. Under NTAP, this additional payment is the lesser of 75% of the costs of REZZAYO, or 75% of the amount by which the costs of the qualifying case exceed the MS-DRG payment, up to a maximum payment of $4,387.50 for a patient treated with REZZAYO per qualifying case.

REZZAYO was granted Qualified Infectious Disease Product (QIDP) designation and was approved by the U.S. Food and Drug Administration under Priority Review on March 22, 2023.  Last year, Melinta acquired the exclusive rights to commercialize REZZAYO in the U.S. from Cidara Therapeutics.  Once-weekly REZZAYO has been available by prescription since July 31, 2023. 

While echinocandins have been available since the early 2000’s, their use has been primarily limited to the hospital inpatient setting due to their requirement of daily IV infusions.  In contrast, REZZAYO is administered as a once-weekly infusion, which may allow appropriate patients to leave the hospital sooner to continue their treatment at home, potentially reducing the burden on patients and the healthcare system. 

“REZZAYO offers a needed option for physicians, and those patients who may be able to transition out of the hospital sooner. The J-Code and NTAP will support broader access to this innovative treatment for patients suffering from invasive Candida infections,” said John Harlow, Melinta’s Chief Commercial Officer. “This is another opportunity for Melinta to deliver on our mission to provide innovative therapies to people impacted by acute and life-threatening illnesses.”   

About REZZAYO™ (rezafungin for injection)  

INDICATIONS AND USE  
REZZAYO is an echinocandin antifungal indicated in patients 18 years of age or older who have limited or no alternative options for the treatment of candidemia and invasive candidiasis. Approval of this indication is based on limited clinical safety and efficacy data.  

REZZAYO has not been studied in patients with endocarditis, osteomyelitis, and meningitis due to Candida.  

IMPORTANT SAFETY INFORMATION  
Contraindications 

REZZAYO™ is contraindicated in patients with known hypersensitivity to rezafungin or other echinocandins. 

Warnings and Precautions 

Infusion-related Reactions: REZZAYO™ may cause infusion-related reactions, including flushing, sensation of warmth, urticaria, nausea, or chest tightness. If these reactions occur, slow or pause the infusion. 

Photosensitivity: REZZAYO™ may cause photosensitivity. Advise patients to use protection from sun exposure and other sources of UV radiation. 

Hepatic Adverse Reactions: Abnormalities in liver tests have been seen in clinical trial patients treated with REZZAYO™. Monitor patients who develop abnormal liver tests and evaluate patients for their risk/benefit of continuing REZZAYO™ therapy. 

Adverse Reactions 

Most common adverse reactions (incidence ≥ 5%) are hypokalemia, pyrexia, diarrhea, anemia, vomiting, nausea, hypomagnesemia, abdominal pain, constipation, and hypophosphatemia. 

Please see full Prescribing Information for REZZAYO™ (rezafungin for injection), available at www.rezzayo.com.  

About Melinta Therapeutics 

Melinta Therapeutics is a biopharmaceutical company dedicated to providing innovative therapies to people impacted by acute and life-threatening illnesses. We focus our expanding portfolio on serving patients with an unmet need because that’s how we make the most meaningful impact. At Melinta, we’re visionaries dedicated to innovation while staying grounded in what matters most: patients. Our portfolio currently includes seven commercial-stage products: BAXDELA® (delafloxacin), KIMYRSA® (oritavancin), MINOCIN® (minocycline) for Injection, ORBACTIV® (oritavancin), REZZAYO™ (rezafungin for injection), TOPROL-XL® (metoprolol succinate) and VABOMERE® (meropenem and vaborbactam). For more information about Melinta Therapeutics, our commitment to patients, and to learn about our portfolio of therapies, visit Melinta.com.   

Melinta Media Relations Contact: 
Sharon Dilling 
Sr. Director, Corporate Communications 
Melinta Therapeutics 

sdilling@melinta.com
609.516.6623 

New Treatment for Candidemia and Invasive Candidiasis Now Available in the U.S

PARSIPPANY, NJ, July 31, 2023 –Melinta Therapeutics, LLC today announced the availability of REZZAYO™ (rezafungin for injection), for the treatment of candidemia and invasive candidiasis in adults with limited or no alternative treatment options. REZZAYO is the first new treatment option approved for patients with candidemia and invasive candidiasis in over a decade. Based on Qualified Infectious Disease Product (QIDP) designation, REZZAYO was approved under Priority Review.  

While echinocandins have been available since the early 2000’s, their use has been primarily limited to the hospital in-patient setting due to their requirement of daily IV infusions.  In contrast, REZZAYO is administered as a once weekly infusion, creating the opportunity for appropriate patients to leave the hospital sooner to continue their treatment at home, potentially reducing the burden on patients and the healthcare system. 

John Harlow, Chief Commercial Officer for Melinta Therapeutics said, “Making REZZAYO available in the U.S. is another way Melinta will leverage our expansive commercial infrastructure and experience launching products and therapies into acute care environments with the ultimate goal of better patient care and outcomes.”   

Last year, Melinta announced that it had acquired the exclusive rights to commercialize REZZAYO in the U.S. from Cidara Therapeutics.  Once-weekly REZZAYO is available by prescription beginning July 31, 2023.    

Harlow added, “The availability of REZZAYO, the first new treatment of its kind in over a decade, is a major step forward in offering healthcare providers a way to simplify and treat patients suffering from invasive Candida infections. It’s a much-needed option for physicians, and those patients who may be able to transition out of the hospital sooner.”     

About REZZAYO™ (rezafungin for injection)  

INDICATIONS AND USE  
REZZAYO is an echinocandin antifungal indicated in patients 18 years of age or older who have limited or no alternative options for the treatment of candidemia and invasive candidiasis. Approval of this indication is based on limited clinical safety and efficacy data.  

REZZAYO has not been studied in patients with endocarditis, osteomyelitis, and meningitis due to Candida.  

IMPORTANT SAFETY INFORMATION  
Contraindications 

REZZAYO™ is contraindicated in patients with known hypersensitivity to rezafungin or other echinocandins. 

Warnings and Precautions 

Infusion-related Reactions: REZZAYO™ may cause infusion-related reactions, including flushing, sensation of warmth, urticaria, nausea, or chest tightness. If these reactions occur, slow or pause the infusion. 

Photosensitivity: REZZAYO™ may cause photosensitivity. Advise patients to use protection from sun exposure and other sources of UV radiation. 

Hepatic Adverse Reactions: Abnormalities in liver tests have been seen in clinical trial patients treated with REZZAYO™. Monitor patients who develop abnormal liver tests and evaluate patients for their risk/benefit of continuing REZZAYO™ therapy. 

Adverse Reactions 

Most common adverse reactions (incidence ≥ 5%) are hypokalemia, pyrexia, diarrhea, anemia, vomiting, nausea, hypomagnesemia, abdominal pain, constipation, and hypophosphatemia. 

Please see full Prescribing Information for REZZAYO™ (rezafungin for injection), available at www.rezzayo.com.  

About Melinta Therapeutics 

Melinta Therapeutics is a biopharmaceutical company dedicated to providing innovative therapies to people impacted by acute and life-threatening illnesses. We focus our expanding portfolio on serving patients with an unmet need because that’s how we make the most meaningful impact. At Melinta, we’re visionaries dedicated to innovation while staying grounded in what matters most: patients. Our portfolio currently includes seven commercial-stage products: BAXDELA® (delafloxacin), KIMYRSA® (oritavancin), MINOCIN® (minocycline) for Injection, ORBACTIV® (oritavancin), REZZAYO™ (rezafungin for injection), TOPROL-XL® (metoprolol succinate) and VABOMERE® (meropenem and vaborbactam). For more information about Melinta Therapeutics, our commitment to patients, and to learn about our portfolio of therapies, visit Melinta.com.   

Melinta Media Relations Contact: 
Sharon Dilling 
Sr. Director, Corporate Communications 
Melinta Therapeutics 

sdilling@melinta.com
609.516.6623