About ContraFect

ContraFect Corporation operates as a clinical-stage biotechnology company. The company focuses on the discovery and development of direct lytic agents ('DLAs'), including lysins and amurin peptides, as new medical modalities for the treatment of life-threatening, antibiotic-resistant infections. The company's first DLA product candidate, exebacase, is being studied in an ongoing Phase 1b/2 study in patients with chronic prosthetic joint infections ('PJIs') of the knee due to S. aureus or coagulase-negative Staphylococci. The company's next product candidate, CF-370, is designed to target a range of gram-negative bacteria, including P. aeruginosa, K. pneumoniae and A. baumannii, and has demonstrated potent in vivo activity against these pathogens, even against multidrug-resistant ('MDR') and extensively drug-resistant ('XDR') strains. Gram-negative pathogens are a major cause of morbidity and mortality in patients with hospital-acquired or ventilator-associated pneumonia and P. aeruginosa remains a major medical challenge for cystic fibrosis patients with chronic lung infections. Portfolio The company intends to develop and commercialize novel therapeutic agents to treat life-threatening infections, including those caused by antibiotic-resistant pathogens. The company has focused its research and discovery efforts on those pathogens that are considered to be urgent or serious threats to global health by the CDC, or considered critical priority by the WHO. The company's DLA product candidates, if successfully developed and approved, will be highly complementary to conventional antibiotics in addressing most of these infections. The company intends to improve outcomes in patient with these life-threatening bacterial infections through use of the company's DLA candidates developed from the company's novel lysin and amurin platforms. Strategy The company's strategy is to use the company's novel, highly differentiated therapeutic DLAs, if approved, to achieve a leading market position in the treatment of life-threatening infectious diseases, including those caused by antibiotic-resistant pathogens. The company plans to pursue commercialization of therapeutic products through discovery, partnerships, acquisitions and development as follows: Evaluate safety and efficacy of exebacase as a treatment for chronic PJIs in the company's Phase 1b/2 study in France. If the Phase 1b/2 study demonstrates positive results, the company would seek to advance exebacase into one or more potential registrational studies, including in the U.S.; Evaluate safety of CF-370 in a Phase 1 study of healthy volunteers. If the results from the Phase 1 studies are positive, the company would seek to advance CF-370 into a Phase 2 study to evaluate the safety and efficacy of CF-370 in one or more patient populations; Advance additional product candidates from the company's portfolio of direct lytic agents targeting gram-negative bacteria, to clinical development as rapidly as possible; Establish partnerships or collaborations to further expand or more rapidly conduct the development of the company's product candidates; Acquire additional technologies that enable the efficient discovery of anti-infective agents; and Acquire clinical stage therapies that treat infectious diseases through unique mechanisms of action. Lead Program: Exebacase (CF-301) Exebacase Development Exebacase is the first lysin to enter U.S. clinical trials and represents a first-in-class anti-bacterial therapeutic candidate. Exebacase was granted Breakthrough Therapy designation for development as a treatment for MRSA bloodstream infections (bacteremia), including right-sided endocarditis, when used in addition to standard-of-care ('SOC') anti-staphylococcal antibiotics in adult patients, by the U.S. Food and Drug Administration ('FDA') in February 2020. The Phase 2 data for MRSA-infected patients treated with exebacase, which demonstrated superior outcomes in clinical response at Day 14 and in 30-day all-cause mortality, as well as health economics benefits, provided the basis for the FDA to grant Breakthrough Therapy designation. In December 2019, the company initiated the Phase 3 DISRUPT (Direct Lysis of S. aureus Resistant Pathogen Trial) superiority design study of exebacase. The DISRUPT study was a randomized, double-blind, placebo-controlled Phase 3 clinical trial conducted in the U.S. alone to assess the efficacy and safety of exebacase in adult and adolescent patients with complicated S. aureus bacteremia, including right-sided endocarditis. Patients entering the study were randomized 2:1 to either exebacase or placebo, with all patients receiving SOC antistaphylococcal antibiotics. The primary efficacy endpoint of the study was clinical response at Day 14 in patients with MRSA bacteremia, including right-sided endocarditis. Secondary endpoints included clinical response at Day 14 in the All S. aureus patient group (MRSA and methicillin-sensitive S. aureus ('MSSA')), 30-day all-cause mortality in MRSA patients, and clinical response at later timepoints. In July 2022, the Data Safety Monitoring Board ('DSMB') of the company's Phase 3 DISRUPT study completed a pre-specified, interim futility analysis and recommended that the DISRUPT study be stopped because the conditional power of the study was below the pre-specified threshold for futility in the DSMB charter. The recommendation was based on an analysis of the clinical response rate at day 14 (the primary efficacy endpoint of the study) in 84 patients, or approximately 60% of the total planned MRSA population with bacteremia, including right-sided endocarditis. Based on the DSMB's recommendation, patient enrollment in the Phase 3 trial was stopped and the trial was closed. The company continued to monitor all already enrolled patients and all patients completed their follow-up visits. The company also expects to complete all clinical study reports as required by the FDA. The company plans to continue to review the totality of the company's clinical data with exebacase in bacteremia patients and the company's internal and external discussions will inform the next steps and any potential opportunities for further development of exebacase for the treatment of S. aureus bacteremia. Clinical Studies Prosthetic Joint Infections On September 30, 2022, the company submitted a Clinical Trial Authorization ('CTA') to the French National Agency for the Safety of Medicines and Health Products ('ANSM') for the study of intra-articular exebacase in patients with chronic prosthetic joint infections of the knee due to S. aureus or coagulase-negative Staphylococci ('CoNS'). The CTA was approved by ANSM in November 2022 and, following IRB/EC approval of the study protocol, the company has recently opened the site in order to initiate dosing of patients. The company expects to report interim clinical data from the first cohort of patients in the second half of 2023. The trial is a Phase 1b/2 study of exebacase in the setting of an arthroscopic debridement with joint retention and systemic antibiotics (DAIR) procedure in patients with chronic PJI of the knee due to S. aureus and/or CoNS. The study is a randomized, double-blind, placebo-controlled two-part clinical study to be conducted at a single center in France to assess the efficacy and safety of exebacase. Part 1 will evaluate the safety, PK, early clinical outcomes, and microbiologic response in patients through Day 42. Up to 2 dose levels of intra-articularly administered exebacase in addition to systemic antibiotics will be studied in up to 2 patient cohorts. Part 2 will consist of a long-term follow-up study of safety and efficacy parameters in patients who complete Part 1 of the study. Follow-up assessments will be performed on Days 90, 180, 360 and 720, including health resource utilization and QoL measures. Patients entering the study will be randomized 3:1 to either exebacase or placebo, with all patients receiving study drug in the setting of a DAIR Procedure. Bacteremia The company has conducted a multi-center Phase 3 clinical study of exebacase for the treatment of S. aureus bacteremia, including right-sided endocarditis, caused by MRSA or MSSA. This randomized, double-blind, placebo-controlled study compared the efficacy, safety and tolerability of exebacase used in addition to SOC antibiotics to SOC antibiotics alone. The study enrolled 259 of the planned 348 patients, who were randomized 2:1 to receive either a single dose of exebacase administered as a 2-hour IV infusion in addition to SOC antibiotics or placebo plus SOC antibiotics. Enrollment in the trial was stopped following a review of the pre-specified, interim futility analysis by the DSMB. No safety concerns were noted by the DSMB. The results from the interim futility analysis were generated based on 84 MRSA bacteremia patients, of which 55 patients were treated with exebacase plus SOC antibiotics (the Exebacase Arm) and 29 patients were treated with placebo plus SOC antibiotics (the SoCA Arm). Topline data showed clinical response at day 14 was 52.7% in the Exebacase Arm compared to 58.6% in the SoCA Arm. The unexpected clinical response in the placebo arm of this study is nearly double the response rate observed in the company's Phase 2 study of exebacase and in prior comparable Phase 3 studies; this was the primary reason the conditional power of the study at the interim futility analysis was below the pre-specified threshold for continuation of the study. The company completed a multi-national Phase 2 clinical study of exebacase for the treatment of S. aureus bacteremia, including endocarditis, caused by MRSA or MSSA. This randomized, double-blind, placebo-controlled study compared the efficacy, safety and tolerability of exebacase used in addition to SOC antibiotics to SOC antibiotics alone. The study enrolled 121 patients randomized 3:2 to receive either a single dose of exebacase administered as a 2-hour IV infusion in addition to SOC antibiotics or placebo plus SOC antibiotics. The primary efficacy analysis population (also known as the microbiological intent-to-treat population, or 'mITT') consisted of 116 patients with confirmed S. aureus infection based on blood culture who received study drug, of which 71 patients received exebacase and 45 patients received placebo. All patients were treated with SOC antibiotics as prescribed by the study investigators, consisting of vancomycin or daptomycin for MRSA and a semi-synthetic penicillin or first-generation cephalosporin for MSSA, prescribed in accordance with treatment guidelines, accepted medical practice and the study protocol. The majority of patients were enrolled in the U.S. (79.3%) with the remainder of patient enrolled from sites in Europe, Latin America, Russia and Israel. A total of 38.8% of exebacase-treated and 35.5% of placebo patients, respectively, had a MRSA infection. The majority of patients in both treatment groups had bacteremia, 77.5% of the exebacase-treated group and 86.7% of the placebo group. Final diagnosis was determined by an independent, blinded clinical adjudication committee. Topline efficacy results from the core study demonstrated the clinical responder rate was 70.4% for patients treated with exebacase and 60.0% for patients treated with SOC antibiotics alone (p=0.314). In a pre-specified analysis of MRSA-infected patients, the clinical responder rate was nearly 43-percentage points higher in the exebacase group compared to the SOC antibiotics alone group (74.1% for patients treated with exebacase compared to 31.3% for patients dosed with SOC antibiotics alone (p=0.010)). In addition to the higher rate of clinical response, MRSA-infected patients treated with exebacase showed a 21-percentage point reduction in 30-day all-cause mortality (p=0.056), a four day lower mean length of hospital stay and meaningful reductions in hospital readmission rates. Phase 1 Clinical Study In 2015, the company concluded a Phase 1 single ascending dose study in healthy volunteers. This trial was a randomized, double-blind, placebo-controlled trial designed to evaluate the safety, tolerability and PK of four different intravenous doses of exebacase. Healthy normal subjects were randomized to receive a single IV dose of exebacase or placebo, each administered as a 2-hour IV infusion. In this Phase 1 study, exebacase was generally well tolerated and there were no clinical adverse safety signals. No SAEs or hypersensitivity adverse events ('AEs') related to exebacase were reported, and no study stopping rules were met. A total of five non-serious AEs were reporting during the study as follows: two subjects who received exebacase reported a total of three non-serious AEs (headache, contact dermatitis, and allergic rhinitis); two subjects who received placebo reported a total of two non-serious AEs (viral upper respiratory tract infection and viral infection). All of these events were mild in intensity and resolved. No patients withdrew from the study due to an AE. There were no clinically relevant changes in inflammatory markers (e.g., erythrocyte sedimentation rate, high sensitivity c-reactive protein, or complement factors, including total hemolytic complement (CH50) associated with exebacase dosing. The company conducted a study evaluating exebacase's ability to eradicate CoNS biomass from clinical isolates of patients with PJIs. The company also conducted a study evaluating exebacase's ability to eradicate S. aureus biofilm from the inside of a hemodialysis catheter removed from an infected patient. Non-Clinical Activities Chemistry, Manufacturing and Controls ('CMC') Exebacase is manufactured using a proprietary engineered E. coli strain that expresses the product in a recombinant manner during the fermentation process. This technology allows production of up to nine grams of exebacase per liter of fermentation broth. After fermentation, the broth containing exebacase is separated and purified through a process containing two chromatographic columns. The resulting product has greater than 99% purity. Safety Pharmacology and Toxicology The company conducted non-clinical safety pharmacology and toxicology studies in connection with the company's Investigational New Drug ('IND') application for exebacase. In these studies, exebacase was well-tolerated in rats for a single two-hour IV administration of doses up to 25mg/kg (determined by the company to be the no observable adverse effect level, or 'NOAEL') and that a single dose of 2.5 mg/kg was not associated with any effects, adverse or not, and was therefore determined to be the no observable effect level ('NOEL'). Exebacase was well tolerated in these studies in both rats and dogs for seven consecutive days of once daily two-hour IV infusions of up to 2.5 mg/kg. In a non-GLP pilot study in rats, 1.0 mg/kg/day was well tolerated for up to seven consecutive days of once daily two-hour IV infusions or IV boluses. Dose-dependent adverse effects were seen in both species at doses above 25 mg/kg/day for 1 day in the rat and above 2.5 mg/kg/day for seven-consecutive days in both the rat and the dog. The dose limiting toxicity observed was a localized microscopic histopathological change surrounding certain blood vessels. In accordance with industry practice, the company has studied exebacase in clinical trials at doses much lower than those that caused adverse effects in animals, and these doses to be within the efficacious range of the drug. Testing for anti-drug antibodies was performed in Phase 1 subjects and Phase 2 patients. No clinical hypersensitivity related to exebacase was observed in subjects dosed in the company's Phase 1, Phase 2 or Phase 3 studies. CF-370: A Novel Engineered Lysin for Infections Caused by Gram-negative Pathogens The company has discovered and engineered a novel lysin, CF-370, an investigational first-in-class anti-bacterial therapeutic candidate targeting gram-negative pathogens. CF-370 has been engineered to bypass the outer membrane of gram-negative bacteria and to enable potent activity in human serum. CF-370 Development The company has studied CF-370 in multiple animal models with external organizations with both sensitive and resistant strains and using CF-370 in addition to either amikacin ('AMK') or meropenem, demonstrating the superiority of the combination of CF-370 with SOC antibiotics in comparison to other agents evaluated in these same models. Key studies and findings are summarized below. The company has studied the in vivo activity of CF-370 against A. baumannii in a neutropenic rabbit pneumonia model. The neutropenic rabbit model was developed to mimic, and therefore potentially translate to, drug activity in immunocompromised patients. CF-370 was well-tolerated and when used in addition to amikacin, demonstrated significant reductions in CFUs in the lungs compared to amikacin alone. The company has also utilized the neutropenic rabbit pneumonia model to study CF-370 against extensively drug-resistant ('XDR') strains of both P. aeruginosa and K. pneumoniae. CF-370 was well-tolerated and when used in addition to amikacin, demonstrated significant reductions in CFUs in the lungs compared to amikacin alone. CF-370 was well-tolerated and when used in addition to meropenem, demonstrated significant reductions in CFUs in the lungs compared to amikacin alone. The results from these studies provide in vivo proof-of-concept for CF-370 as a potential treatment for pulmonary infections caused by gram-negative pathogens and for direct lytic agents as a potential new modality to combat the threat of multidrug-resistant gram-negative pathogens. The company plans to continue to progress CF-370 through IND-enabling activities and the company expects it to be its next molecule in clinical studies. The company plans to submit an IND application with the FDA in the second quarter of 2023 and, if approved, to initiate phase 1 clinical studies of CF-370 in healthy volunteers shortly thereafter. Discovery Platform The company's approach includes the use of lysins in addition to conventional antibiotics for the treatment of serious, drug-resistant bacterial infections, including biofilm-associated infections, in an effort to achieve greater efficacy and improve clinical outcomes, as well as potentially protect against antibiotic resistance. The company employs bioinformatics and a series of metagenomic-based techniques to identify lysins from bacterial, viral, and environmental sources. The field of metagenomics is based on the bulk extraction of DNA/RNA from environmental samples (e.g., soil, water, etc.) without prior isolation of individual microbial sources. This is useful when one considers that less than 1% of microbes are culturable under standard laboratory conditions. Once extracted, the metagenomic DNA can then be examined using sequence-based methods or by proprietary functional screens. These functional screens for lysin activity form the major component of the company's lysin discovery work. Once cloned, the company's scientists also employ a variety of techniques to further optimize and 'engineer' changes to the lysins to introduce specific characteristics, which may be favorable for potential therapeutic use. For the functional metagenomic work that the company performs, environmental genes are expressed in a recombinant format in a standard host organism (i.e., Escherichia coli) and cells are monitored for the acquisition of a desired phenotype. The company can vary both the source of environmental DNA and the way the company monitors for desired phenotypes to focus only on environmental populations enriched for bacteriophage lysins that can actively kill a pathogen of interest. The company samples various DNA sources, including viral, prophage, and pathogen-amplified viral metagenomics. Multiple methods for both DNA library construction and for functional screening are used in parallel in order to maximize lysin identification. The application of these methods enables the large-scale identification of lysins, enabling the production of lysin banks specific for any particular pathogen. The ability to rapidly identify lysins specific for any pathogen of interest, either by in vitro or in silico methods, will provide a steady pipeline of novel lysins for consideration as potential antimicrobial therapeutic candidates. Amurin peptides are another class of novel, phage-derived lytic agents discovered in the company's laboratories. In preclinical studies, amurin peptides have shown some features common to lysins, including potent bacteriocidality, including antibiotic-resistant strains, the ability to clear biofilms and synergize with conventional antibiotics. Amurin peptides have shown the potential to exert these actions on the full range of gram-negative ESKAPE pathogens, as well as a range of additional, serious and difficult to treat gram-negative bacteria, including some strains of Burkholderia and Stenotrophomonas, in the context of human serum, without apparent 'off target' effects against gram-negatives. As such, amurin peptides would be extremely well suited as potential treatments for patients suffering from polymicrobial gram-negative infections, such as cystic fibrosis, ventilator-associated pneumonia, intra-abdominal infections, and serious burns or certain chronic wound infections. Given their powerful in vitro activity against a broad range of resistant pathogens, amurin peptides have the potential to become a powerful addition to the company's armamentarium against strains of gram-negative pathogens which have extreme-or pan- drug resistance to all or almost all available antibiotics. The company plans to further progress agents from the company's amurin peptide program when adequate funding becomes available. The focus of the company's research and discovery efforts is on identifying lysins which selectively kill specific species of gram-negative bacteria that are considered to be urgent or serious threats to global health by the CDC or critical priorities by the WHO. Emerging strains of multi-drug resistant gram-negative pathogens that are resistant to all or nearly all available antibiotics are considered to be a major global health threat. The company believe that lysins targeting gram-negative pathogens have the potential to be important therapeutics to combat antimicrobial resistance due to their novel mechanism of action and therapeutic profile, which is complementary to conventional antibiotics. Intellectual Property The company's portfolio consists of thirty (30) U.S. patents, one-hundred and fifty-four 154) issued foreign patents and two hundred and fourty-six (246) pending U.S. and international patent applications that the company has licensed from Rockefeller and/or developed in-house. The company's patents and patent applications include those that are directed to compositions and methods for the treatment of infections caused by Gram-positive bacteria (Group B Streptococci, S. aureus, Streptococcus pneumonia, Bacillus anthracis (anthrax), Enterococcus faecalis and Enterococcus faecium) and infections caused by Gram-negative bacteria (P. aeruginosa, K. pneumoniae, Enterobacter cloacae and E. coli). If patents are granted on the company's patent applications, which include certain patent applications related to exebacase, CF-296 and the Gram-negative lysins, they would expire between 2029 and 2042. For exebacase, the company's issued patent with composition of matter claims and issued patent with method claims for killing S. aureus strains both provide protection through 2032, the company's issued patent with method claims for disrupting or treating biofilm provides protection until 2033 and additional patents, if issued as the company expects, could provide further protection beyond 2033. For CF-370, the company's issued patent with composition of matter and method claims for killing P,aeruginosa strains provides protection until 2039. The company's patent applications with further method of use claims directed to Gram-negative strains, which include K. pneumoniae, A. baumannii, Enterobacter cloacae, E. coli, and S. maltophilia, if granted, could provide protection beyond 2039. License Agreements-The Rockefeller University The company has entered into the following license agreements with Rockefeller: On July 12, 2011, the company entered into a license agreement for the worldwide, exclusive right to a provisional patent application, upon which a non-provisional patent application has since been filed, covering the composition of matter for the lysin PlySS2 for the treatment and prevention of diseases caused by gram-positive bacteria (the 'CF-301 License'). The company rebranded PlySS2 as CF-301, or exebacase. This license gives the company the right to exclusively develop, make, have made, use, import, lease, sell and offer for sale products that would fall within the scope of claims in the patent application or otherwise infringe a claim of the patent. On June 1, 2011, the company entered into a license agreement for the exclusive rights to Rockefeller's interest in a joint patent application, which have granted patents covering the method of delivering antibodies through the cell wall of a gram-positive bacteria to the periplasmic space. This intellectual property was developed as a result of the sponsored research agreement between the company and Rockefeller, and was jointly discovered and filed by the two parties. On September 23, 2010, the company entered into a license agreement for the worldwide, exclusive right to develop, make, have made, use, import, lease and sell, and offer for sale products that would otherwise infringe or fall within the scope of a claim of the suite of patents and patent applications covering the composition of matter for eight individual lysin molecules for the treatment and prevention of diseases caused by gram-positive bacteria. The lysins in this suite have activity against Group B Streptococci, S. aureus, Streptococcus pneumonia, Bacillus anthracis, Enterococcus faecalis and Enterococcus faecium. Government Regulation The FDA and other regulatory authorities at federal, state, and local levels, as well as in foreign countries, extensively regulate, among other things, the research, development, testing, manufacture, quality control, import, export, safety, effectiveness, labeling, packaging, storage, distribution, record keeping, approval, advertising, promotion, marketing, post-approval monitoring, and post-approval reporting of biologics, such as those the company is developing. Drug and biologic manufacturers and their subcontractors are required to register their establishments with the FDA and certain state agencies, and are subject to periodic unannounced inspections by the FDA and certain state agencies for compliance with cGMPs, which impose certain procedural and documentation requirements upon the company and its third-party manufacturers. To obtain regulatory approval of an investigational medicinal product under EU regulatory systems, the company must submit a marketing authorization application, or MAA. Research and Development The company recorded $44.7 million of research and development expenses for the year ended December 31, 2022. History ContraFect Corporation was founded in 2008. The company was incorporated as a Delaware corporation in 2008.