Table of Contents

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References to ContraFectREFERENCES TO CONTRAFECT

Throughout this Annual Report on Form10-K, the “Company,” “ContraFect,” “we,” “us,” and “our,” except where the context requires otherwise, refer to ContraFect Corporation, and “our board of directors” refers to the board of directors of ContraFect Corporation.

All brand names or trademarks appearing in this Annual Report on Form10-K are the property of their respective holders.

Forward Looking InformationFORWARD LOOKING STATEMENTS

The information in this Annual Report on Form10-K contains forward-looking statements and information within the meaning of Section 27A of the Securities Act of 1933, as amended, or the Securities Act, and Section 21E of the Securities Exchange Act of 1934, as amended, or the Exchange Act, which are subject to the “safe harbor” created by those sections. These forward-looking statements include, but are not limited to, statements concerning our strategy, future operations, future financial position, future revenues, our ability to continue as a going concern, projected costs, prospects and plans and objectives of management. The words “anticipates”, “believes”, “estimates”, “expects”, “intends”, “targets”, “may”, “plans”, “projects”, “potential”, “will”, “would”, “could” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. All such forward-looking statements involve significant risks and uncertainties, including, but not limited to, statements regarding:

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As more fully described under the heading “Risk Factors” contained elsewhere in this Annual Report on Form10-K, many important factors affect our ability to achieve our stated objectives and to develop and commercialize any product candidates. We may not actually achieve the plans, intentions or expectations disclosed in our forward-looking statements and you should not place undue reliance on our forward-looking statements. These forward-looking statements involve risks and uncertainties that could cause our actual results to differ materially from those in the forward-looking statements, including, without limitation, the risks and uncertainties set forth in our filings with the SEC. You should read this Annual Report on Form10-K and the documents that we have filed as exhibits to this Annual Report on Form10-K completely and with the understanding that our actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward-looking statements that we make. The forward-looking statements are applicable only as of the date on which they are made, and we do not assume any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law.

RISK FACTOR SUMMARY

iiOur business is subject to numerous risks and uncertainties, including those described in Part I, Item 1A. “Risk Factors” in this Annual Report on Form 10-K. You should carefully consider these risks and uncertainties when investing in our common stock. The principal risks and uncertainties affecting our business include the following:

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We are a clinical-stage biotechnology company focused 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. Antibiotic-resistant infections account for 2,000,000 illnesses in the United States and 700,000 deaths worldwide each year. We intend to address antibiotic-resistant infections using product candidates from our lysin and amurin peptide platforms. We believe DLAs are fundamentally different than antibiotics and offer a potential paradigm shift in the treatment of antibiotic-resistant infections. According to one of the most recent and comprehensive reports on the global burden of bacterial antimicrobial resistance (“AMR”), there were an estimated 4.95 million deaths associated with bacterial AMR in 2019, including 1.27 million deaths directly attributable to bacterial AMR. The six leading pathogens for deaths associated with resistance (Escherichia coli (“E. coli”), Staphylococcus aureus (“S. aureus”), Klebsiella pneumoniae (“K. pneumoniae”), Streptococcus pneumoniae, Acinetobacter baumannii (“A. baumannii”), and Pseudomonas aeruginosa (“P. aeruginosa”)) were responsible for 929,000 deaths. Only one pathogen–drug combination, methicillin-resistant S. aureus (“MRSA”), caused more than 100,000 deaths in 2019.

Our first DLA product candidate, exebacase, is currently 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. In addition to PJIs, Staphylococci, and S. aureus in particular, is also a common cause of bacteremia, pneumonia and osteomyelitis as well as biofilm-associated infections of heart valves (endocarditis), indwelling devices and catheters. These infections result in significant morbidity and mortality despite currently available antibiotic therapies.

Our 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.

Lysins are recombinantly-produced enzymes, thatenzymes; when applied to bacteria, they cleave a key component of the target bacteria’s peptidoglycan cell wall, resulting in rapid bacterial cell death. In addition to the speed of action and potent cidality, we believe lysins are differentiated by their other hallmark features, which include the demonstrated ability to eradicate biofilms and synergistically boost the efficacy of conventional antibiotics in animal models. Lysins also tend to have a “targeted spectrum,” meaning they kill only specific species of bacteria or closely related bacteria. Amurin peptides are a new class of DLAs, discovered in our laboratories, which disrupt the outer membrane of gram-negative bacteria, resulting in rapid bacterial cell death, offering a distinct mechanism of action from lysins. Amurins are further differentiated from lysins byhave a potent, “broad spectrum”broad spectrum of in vitro activity against a wide range of gram-negative pathogens, in, including deadly, drug-resistantPseudomonasP. aeruginosa (“P. aeruginosa”),KlebsiellaK. pneumoniae, EscherichiaE. coli, AcinetobacterA. baumanniiand Enterobacter cloacaebacteria species as well as difficult to treat pathogens such asStenotrophomonas,Achromobacter and some Burkholderiaspecies. The highly differentiated properties of DLAs have shown these agents to be complementary to and synergistic with conventional antibiotics enablingunderscore their potential use in addition to antibiotics with the goal of improving clinical outcomes compared to antibiotics alone. The development of DLAs involves a novel clinical and regulatory strategy, using superiority design clinical trials with the goal of delivering significantly improved clinical outcomes for patients with serious and/or antibiotic-resistant bacterial infections, including biofilm-associated infections. We believe this approach affords potential clinical benefits to patients as well as the potential ability to mitigate against further development of antibiotic resistance.

Our most advanced clinical candidate, exebacase, is an investigational novel lysin that targetsStaphylococcus aureus (“Staph aureus”), including methicillin-resistant (“MRSA”) strains, which causes serious infections such as bacteremia, pneumonia and osteomyelitis.Staph aureus is also a common cause of biofilm-associated infections of heart valves (endocarditis), prosthetic joints, indwelling devices and catheters. These infections result in significant morbidity and mortality despite currently available antibiotic therapies. Exebacase completed a Phase 2 superiority study that evaluated its safety, tolerability, efficacy and pharmacokinetics (“PK”) when used in addition to background standard of care (“SOC”) antibiotics compared to SOC antibiotics alone for the treatment ofStaph aureus bacteremia, including endocarditis in adult patients. In January 2019, we announced topline results from this study which showed clinically meaningful improvement in clinical responder rates among patients treated with exebacase in addition to SOC antibiotics compared to SOC antibiotics alone.

In the Phase 2 study, the primary efficacy analysis population of 116 patients with documentedStaph aureusbacteremia, including endocarditis, who received a single intravenous (“IV”) infusion of blinded study drug, the clinical responder rate at Day 14 was 70.4% for patients treated with exebacase and 60.0% for patients dosed with SOC antibiotics alone (p=0.314). The clinical responder rate at Day 14 in the subset of patients with bacteremia including right-sided endocarditis was 80.0% for patients treated with exebacase compared to 59.5% for patients treated with SOC antibiotics alone, an increase of 20.5% (p=0.028). In the subset of patients with bacteremia alone, the clinical responder rate at Day 14 was 81.8% for patients treated with exebacase compared to 61.5% for patients treated with SOC antibiotics alone, an increase of 20.3% (p=0.035). In apre-specified analysis of MRSA-infected patients, the clinical responder rate at Day 14 in patients treated with exebacase was nearly43-percentage points higher than in patients treated with SOC antibiotics alone (74.1% for patients treated with exebacase compared to 31.3% for patients treated with SOC antibiotics alone (p=0.010)). In addition to the higher rate of clinical response, MRSA-infected patients treated with exebacase showed a21-percentage point reduction in30-dayall-cause mortality (p=0.056), a four day lower mean length of hospital stay and meaningful

antibiotic-resistant infections was approximately $21 billion to $34 billion annually, a substantial portion of which is due to increased length of hospital stays necessary to treat these patients. Antibiotic resistance has limited the effectiveness of many conventional antibiotics andantibiotics; the discovery and development of new therapeutics to address resistance has not kept pace with the increasing incidence of thesedifficult-to-treat microbial infections. As Dr. Tedros Adhanom Ghebreyesus, Director-General of WHO, has accordingly stated, “never has the threat of antimicrobial resistance been more immediate and the need for solutions more urgent. Numerous initiatives are underway to reduce resistance, but we also need countries and the pharmaceutical industry to step up and contribute with sustainable funding and innovative new medicines.”

We take this mandate very seriously and have focused our 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. In particular, species of bacteria that are part of the ESKAPE pathogens (Enterococcus faecium,Staphylococcus aureus,Klebsiella pneumoniae,Acinetobacter baumannii,Pseudomonas aeruginosa,andEnterobacter species) are urgent or serious threats, and are also the leading causes of hospital acquired infections throughout the world. We believe that DLAsour DLA product candidates, if successfully developed and approved, will be highly complementary to conventional antibiotics in addressing most of these infections. We aim to improve outcomes in patient with these life-threatening bacterial infections through use of our DLA candidates developed from our novel lysin and amurin platforms.

We continue to advance novel lytic agents across our portfolio. We initiated the single Phase 3 DISRUPT study of exebacase in December 2019. We also expanded the investigator-initiated early access program for compassionate use of exebacase for individual named patients with chronic post-operative prosthetic joint infections (“PJIs”) under Temporary Authorizations for Use from the French National Agency for Medicines and Health Products Safety in collaboration with Dr. Tristan Ferry at the Hôpital de la Croix Rousse in Lyon, France. We have developed a novel, engineered variant of exebacase, known asCF-296, which we believe provides an additional opportunity to advance a potential targeted therapy for deep-seated, invasive biofilm-associatedStaph aureus infections. We are conducting furtherin vitro andin vivo characterization ofCF-296 to evaluate the full profile of this compound. We have been awarded up to $7.2 million of funding from the Military Infectious Diseases Research Program, United States Army Medical Research and Development Command (“USAMRDC”) over the course of three years to advanceCF-296 through Investigational New Drug application (“IND”)-enabling studies.

We have discovered and engineered a new lysin product candidate,CF-370, which in preclinical studies has demonstrated potent activity against antibiotic-resistantP. aeruginosabacteria, a major cause of morbidity and mortality in patients with hospital acquired pneumonia and a major medical challenge for patients with cystic fibrosis. We have initiatedIND-enabling activities and we expectCF-370 to be our next molecule in clinical studies. We have been awarded up to $3.3 million in funding fromCARB-X (Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator) in support of the advancement of anti-pseudomonal lysins. Beyond our lysin programs, we continue our research to advance potential product candidates from our amurin peptide platform. We will be initiating animal studies of our most promising amurins with the goal of moving this program into clinical studies as soon as possible. We have been awarded up to $6.9 million of funding fromCARB-X to support the amurin peptide program. In summary, we now have three modalities within the DLA therapeutic umbrella, including (i) native lysins for gram-positive pathogens (ii) engineered lysins forgram-negative pathogens and (iii) amurins for a wide spectrum of gram-negative pathogens.

Our Lead Program: Exebacase(CF-301)

Medical OpportunityOpportunities

StaphProsthetic Joint Infections

Prosthetic joint infection (“PJI”) is a devastating complication following total joint arthroplasty (“TJA”), either total knee arthroplasty (“TKA”) or total hip arthroplasty (“THA”). It is a leading cause of morbidity and revision following TJA and a significant driver of healthcare costs. There are over 100,000 orthopedic prosthesis-related infections annually in the U.S., representing approximately 2-3% of joint replacement patients; the prevalence of PJI related to resistant organisms is increasing. More importantly, Staphylococcus is the primary infecting organism and treatment failure is due to the presence of biofilms, or the protective structures that allow bacteria to “stick” to implanted devices and shield themselves from both the immune system and conventional antibiotics.

Once PJI is diagnosed, two-stage exchange arthroplasty remains the gold standard for treating PJI, since there is a high rate of treatment failure with current irrigation and debridement or one-stage exchange arthroplasty procedures. A two-stage exchange involves removal of the infected artificial joint components along with bone and soft tissue, followed by 12-16 weeks of IV and oral antibiotic therapy before a new artificial joint can be implanted. Unfortunately, systemic antibiotics are often unable to eradicate biofilms, resulting in poor outcomes. PJI significantly reduces the long-term quality of life (“QoL”) and the high failure rates ultimately result in arthrodesis, amputation, or mortality. In fact, PJI is associated with a 5-year mortality rate higher than that of breast cancer, melanoma, Hodgkin’s lymphoma, and other common malignancies.

In addition to the significant morbidity and mortality associated with PJI, the cost of treating PJI is substantial, with estimated annual hospital costs expected to increase to over $1.1 billion for TKA and to over $750 million for THA by 2030. Mean PJI treatment cost is approximately 3 to 4 times that for primary joint replacement, and when the causative pathogen is a resistant organism, such as MRSA, the mean PJI treatment cost increases nearly 60% compared to PJI caused by more susceptible microorganisms.

Bacteremia

S. aureus bacteremia is a serious bacterial infection associated with high morbidity and mortality. In the U.S. alone, there are approximately 200,000 hospitalizations forStaphS. aureus bacteremia annually. Mortality

often unsuccessful and necessitate surgery to eradicate bacteria from infected heart valves. Mortality attributed toStaphS. aureus bacteremia is higher when the infection is caused by MRSA as compared to methicillin-susceptible S. aureus(“MSSA”)Staph aureus. MRSA is considered a serious threat to global health by the CDC and a high priority threat by the WHO. Emerging resistance to conventional antibiotics such as vancomycin and daptomycin, which are used to treat MSSA and MRSA, represents an additional serious threat which may have serious consequences in terms of increasing morbidity, mortality and health care utilization.

Exebacase Development

Exebacase is the first lysin to enter U.S. clinical trials and represents a first-in-class anti-bacterial therapeutic candidate. Exebacase has beenwas granted both Breakthrough Therapy and Fast Track designations by the FDAdesignation for thedevelopment as a treatment offor MRSA bloodstream infections (bacteremia), including right-sided endocarditis, when used in addition to SOCstandard-of-care (“SOC”) anti-staphylococcal antibiotics in adult patients. Ifpatients, 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, we are ableinitiated 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 obtain regulatory approvalassess 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 this initial indication, we believefutility 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. We continued to monitor all already enrolled patients and all patients completed their follow-up visits. We also expect to complete all clinical study reports as required by the FDA.

We plan to continue to review the totality of our clinical data with exebacase and/or engineered variants, may bein bacteremia patients and our internal and external discussions will inform the next steps and any potential opportunities for further developeddevelopment of exebacase for the treatment of other serious diseases caused byStaphS. aureus including biofilm-related infections in prosthetic joints and indwelling devices, as well as pneumonia and osteomyelitis. bacteremia.

Clinical Studies

Prosthetic Joint Infections

On September 30, 2022, we 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, we have recently opened the site in order to initiate dosing of patients. We expect to report interim clinical data from the first cohort of patients in the second half of 2023.

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The trial is a Phase 3 Clinical Study1b/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

We are conductinghave conducted a multi-center Phase 3 clinical study of exebacase for the treatment ofStaphS. aureus bacteremia, including right-sided endocarditis, caused by MRSA or MSSA. This randomized, double-blind, placebo-controlled study comparescompared the efficacy, safety and tolerability of exebacase used in addition to SOC antibiotics to SOC antibiotics alone. The study is targeting enrollmentenrolled 259 of approximately 350the planned 348 patients, who were randomized 2:1 to receive either a single dose of exebacase administered as a2-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 our 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.

Demographically, the two arms were well balanced in most baseline factors including final diagnosis, primary source of infection, risk factors for bacteremia, SOC antibiotic used and age. There was an imbalance in the baseline disease severity of patients with MRSA bacteremia, as determined by the APACHE II score, with 34.8% of patients in the Exebacase Arm having an APACHE II score >15 at randomization, as compared to only 13.8% of patients in the SoCA Arm. A patient with an APACHE II score above 15 is considered to have an extremely poor prognosis and a significantly increased risk of mortality. Subgroup analyses of clinical response were all as expected, based on the topline results, other than APACHE II subgroups.

All patients have completed all study visits, and all patient outcomes have been verified by the blinded adjudication committee. The full results of the study, including the primary efficacy endpoint is clinicalof the study (clinical response at Day 14 in patients with MRSA bacteremia, including right-sided endocarditis. Secondarybacteremia), secondary endpoints include clinical(clinical response at Day 14 in the AllStaphS. aureuspatient group (MRSA and MSSA),30-dayall-cause30-day all-cause mortality in MRSA patients,patients), and clinical response at Day 30 and Day 60 in both the MRSA and the AllStaph aureus patient group. A summary of the statistical parameters of the key efficacy endpoints is shown in Table 1 below.

Table 1

Clinical response is defined by objective clinical response criteria including (1) resolution of signs and symptoms attributablelater timepoints are expected toStaph aureus bacteremia/right-sided endocarditis (“SAB/RIE”) that were present at

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 apre-specified analysis of MRSA-infected patients, the clinical responder rate was nearly43-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 a21-percentage point reduction in30-dayall-cause30-day all-cause mortality (p=0.056), a four day lower mean length of hospital stay and meaningful reductions in hospital readmission rates.

The clinical responder rate in the subset of patients with bacteremia, including right-sided endocarditis was 80.0% for patients treated with exebacase compared to 59.5% for patients treated with SOC antibiotics alone, an increase of 20.5% (p=0.028). Similarly, in the subset of patients with bacteremia alone, the clinical responder rate was 81.8% for patients treated with exebacase compared to 61.5% for patients treated with SOC antibiotics alone, an increase of 20.3% (p=0.035).

We conducted a pilot study evaluating exebacase’s ability to eradicateStaph CoNS biomass from clinical isolates of patients with PJIs. Figure 1 below shows the anti-biomass activity of exebacase in addition to SOC antibiotics compared to exebacase and antibiotics alone against S. epidermidis biofilms from 19 isolates. Remaining biomass after 24 h of exebacase exposure at 5, 50, and 150 mg/L, and/or rifampicin at 1 mg/L, vancomycin at 10 mg/L, and daptomycin 10 mg/L, was evaluated by crystal violet staining. All isolates treated with exebacase, whether alone or in addition to SOC antibiotics demonstrated statistically significant decreases in biomass (***P < 0.001) over SOC antibiotics alone.

Figure 1: Anti-Biomass Activity of Exebacase and SOC Antibiotics Against CoNS Biofilms

We 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. The endpoint of the model was a reduction in the amount of bacteria (measured in CFUs). Segments of the catheter were assigned to one of three different treatment groups: exebacase, daptomycin (DAP) or exebacase + DAP at the clinically relevant concentration of 1 µg/mL. As shown in Figure 12 below, exebacase eradicated the biofilm at 1 µg/mL whereas daptomycin alone did not clear biofilm at 1 µg/mL. The addition of exebacase with daptomycin resulted in the same clearance of biofilm as exebacase alone. The catheter biofilm contained MRSA as well as other Staph species. We believe these data provide important translation of the previously reported potent efficacy of exebacase against biofilms formed in vitro and in animal models, to biofilms formed in the setting of human disease.

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Figure 1:2: Sensitivity of MRSA Biofilms on Explanted Human Catheter to Exebacase(CF-301)

In view of the lack of efficacy of conventional antibiotics against biofilms, we believe exebacase, if approved, may provide an important new therapeutic option to address the biofilm components of invasiveStaph aureus infections and potentially forestall or eliminate the need for surgical intervention.

Rapid, potent and selective bactericidal activity

Lysins have demonstrated rapid bactericidal activity. We have performed timekill assays comparing the time it has taken exebacase to kill bacteriaintervention in vitroand exert a bactericidal effect to the time required for daptomycin or vancomycin to do the same. All drugs were administered at a concentration of 1x minimal inhibitory concentration (“MIC”). Exebacase reduced the number ofStaph aureus bacteria in tests on 62 strains

Figure 3: Study of nine animals treatedExebacase with exebacase andDaptomycin in Rabbit Implant-Associated Osteomyelitis Model

Bacterial burden of the bone		Bacterial burden on implant

*p<0.0025 vs vehicle control; **p<0.0098 vs daptomycin were found to have sterilized kidney, spleen and heart valve vegetations, whereas none of the animals treated with daptomycin alone had tissues that were sterilized.

We have subsequently conducted additional experiments at UCLAa study in the rabbit infective endocarditis model in order to both replicate the results of the rat study, but also to examine a range of exebacase doses used in addition to daptomycin as compared to both buffer and daptomycin alone. The results of a dose-ranging study, where a range of single doses of exebacase was assessed when administered in addition to four days of daptomycin treatment are shown in Figure 24 below. As seen in the rat studies, administration of daptomycin alone resulted in a3-log reduction in CFUs in the heart valve vegetations in these animals infected with MRSA. The addition of a single dose of exebacase, resulted in an additional~3-log reduction in CFUs in the cardiac vegetations compared to daptomycin alone at all doses of exebacase tested (p< 0.002). Using conventional allometric scaling, the 0.7 mg/kg dose of exebacase approximates the human clinical dose of 0.25mg/kg, which is the dose being studied in our Phase 2 clinical trial. This dose together with daptomycin resulted in a6-log reduction in CFUs compared to buffer (p< 0.001). Of note, efficacy was maintained even at the lowest dose of exebacase tested (0.09 mg/kg) in this study (p< 0.001).

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Endocarditis Model

Upon first exposure to exebacase, no hypersensitivity reaction was observed in any of our animal studies. Upon administration of a second course of exebacase, given two weeks after completion of the first course, includingmultiple-day courses, hypersensitivity or hypersensitivity-like findings were observed in mice, rats and dogs. In a dedicated hypersensitivity study in rats, using a model intended to elicit hypersensitivity, findings consistent with hypersensitivity were observed after atwo-week delayedre-challenge with a second course of exebacase and were not dose-dependent. In general, in humans, Type I hypersensitivity is an allergic anaphylaxis-like response (e.g., an immediate and potentially life-threatening allergic reaction) and Type III hypersensitivity is a serum sickness-like response (e.g., fever, joint pain, protein in urine, vascular changes). While the nature of hypersensitivity reactions in rats may not necessarily be predictive of hypersensitivity reactions that may occur in humans, we have also considered the risk of hypersensitivity occurring upon first administration of exebacase due to potential prior exposure to the active protein component of exebacase from the environment, as it is a naturally occurring protein. Testing for anti-drug antibodies was performed in Phase 1 subjects.subjects and Phase 2 patients. No clinical hypersensitivity related to exebacase was observed in subjects dosed in our Phase 1, Phase 2 or Phase 2 study.

Acinetobacter baumannii (“A. baumannii”)

A. baumannii is an investigationalfirst-in-class anti-bacterial therapeutic candidate targeting a gram-negative pathogen.CF-370 haspathogen which poses a particularly challenging threat to hospitalized patients because it frequently contaminates healthcare facility surfaces and shared medical equipment. A. baumannii is already resistant to many antibiotics, including carbapenems, which further reduces patient treatment options. Carbapenem-resistant strains can produce carbapenemases, which are enzymes that break down carbapenems and make them ineffective; these can spread to other gram-negative bacteria and amplify the problem of resistance through mobile resistance elements, appear to be increasing in incidence, with over 60% of all healthcare-associated A. baumannii infections being multi-drug resistant.

A. baumannii is a leading cause of VAP as well as bloodstream and wound infections. Invasive infections, especially in carbapenem-resistant strains, are consistently associated with high mortality. In China, mortality rates up to 55.7% have been engineeredreported in patients with A. baumannii infections and up to bypass36.5% of deaths are considered to be directly attributable to the outer membraneinfection.

Enterobacteriaceae

The Enterobacteriaceae familyof gram-negative bacteriaincludes Klebsiella pneumoniae (“K. pneumoniae”), Enterobacter species (“Enterobacter” e.g. Enterobacter cloacae) and Escherichia coli (“E. coli”), all of which can cause serious, life-threatening infections, and have demonstrated concerning resistance patterns.

Enterobacteriaceae canproduce enzymes (e.g., “extended-spectrum beta-lactamases (“ESBL”)) that confer resistance to most beta-lactam antibiotics, including penicillins, cephalosporins, and the monobactam aztreonam. Infections with ESBL-producing organisms have been associated with poor outcomes. Approximately 20% of K. pneumoniae infections and 31% of Enterobacter infections in intensive care units in the United States now involve strains which are not susceptible to third-generation cephalosporins. Community and hospital-acquired ESBL-producing Enterobacteriaceae are prevalent worldwide, and their prevalence may be underestimated because reliable identification of ESBL-producing organisms in clinical laboratories can be challenging.

Carbapenem antibiotics are considered to be the best currently available antimicrobial agent to treat infections caused by ESBL-producing Enterobacteriaceae. However, resistance to carbapenems is becoming increasingly prevalent, and the resulting Carbapenem-resistant Enterobacteriaceae (“CRE”), have high levels of resistance to antibiotics. K. pneumoniae and E. coli are a normal part of the human gut bacteria that can become carbapenem-resistant due to enzymes that breakdown carbapenem antibiotics and make them ineffective. These enzymes have also been reported in P. aeruginosa and A. baumannii infections. CRE infections typically occur in hospitals, nursing homes, and other healthcare settings. Patients who require devices like ventilators or catheters, and/or patients who are taking long courses of certain antibiotics are most at risk for CRE infections. Some CRE bacteria have become resistant to most available antibiotics, are very difficult to treat, and can lead to death in up to 50% of patients who become infected.

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CF-370 Development

We believe agents that target P. aeruginosa, K. pneumoniae, Enterobacteriaceae and E. coli will be important therapeutic options for the treatment of serious, potentially life-threatening invasive infections caused by multidrug resistant pathogens. Because of the novel mechanism by which direct lytic agents are designed to kill bacteria and the lack of observable cross resistance to enable potentconventional antibiotics, KPC, NDM and similar enzymes are not expected to have any effect on the activity of our investigational agents. We believe that direct lytic agents help to improve clinical outcomes and decrease mortality of infections caused by these pathogens.

We have 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.

We have 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 human serum. 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 as seen in Figure 5 below.

Figure 5: Study of CF-370 with Amikacin in a Neutropenic Rabbit Pulmonary Model of A. baumannii Infection

We have also utilized the neutropenic rabbit pneumonia model to study CF-370 against extensively drug-resistant (“XDR”) strains of both P. aeruginosa and K. pneumoniae as seen in Figures 6 and 7 below.

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Figure 6: Study of CF-370 with Amikacin in a Neutropenic Rabbit Pulmonary Model of XDR P. aeruginosa Infection

CF-370 was well-tolerated and when used in addition to amikacin, demonstrated significant reductions in CFUs in the lungs compared to amikacin alone as seen in Figure 6 above.

Figure 7: Study of CF-370 with Amikacin in a Neutropenic Rabbit Pulmonary Model of XDR K. pneumoniae Infection

CF-370 was well-tolerated and when used in addition to meropenem, demonstrated significant reductions in CFUs in the lungs compared to amikacin alone as seen in Figure 7 above.

We believe this isthe results from these studies provide in vivoproof-of-concept for CF-370 as a significant milestonepotential treatment for pulmonary infections caused by gram-negative pathogens and for direct lytic agents as native lysins are typically unablea potential new modality to penetratecombat the outer membranethreat of multidrug-resistant gram-negative bacteria and consequently unablepathogens. We plan to workin vitro in human blood or in animal models. However, based on the proprietary methods we have identified and utilizecontinue to engineer lysins,progress CF-370 has exhibited the hallmarkin vitro features of the lysin class, including rapid and potent bactericidal activity, synergy with a broad range of standard of care agents and the eradication of biofilms in preclinical studies. In preclinical rabbit pneumonia models, single doses ofCF-370 alone and in combination with meropenem, were tested against multi-drug resistantP. aeruginosa to evaluate survival and bacterial burden in lung and secondary organs. In these models, strong activity was observed forCF-370 as a monotherapy, showing that rabbits dosed withCF-370 alone had longer survival, as compared to vehicle control, and reductions in bacterial burden in the lung, kidney and spleen with single doses ofCF-370. Synergy with meropenem was also noted with greater reductions in bacterial burden compared to monotherapy. In these models,CF-370 was well tolerated with no adverse clinical consequences and no deaths among animals infected withP. aeruginosa.

We have advancedCF-370 into through IND-enabling activities and we expect it to be our next molecule in clinical studies. We have been awarded upplan to $3.3 millionsubmit an IND application with the FDA in funding fromCARB-Xthe second quarter of 2023 and, if approved, to initiate phase 1 clinical studies of CF-370 in support of the advancement of anti-pseudomonal lysins.

(Enterococcus faecium,Staphylococcus aureus,Klebsiella pneumoniae,Acinetobacter baumannii,Pseudomonas aeruginosa, andEnterobacter species), which are the leading causes of hospital acquired infections throughout the world.

LysinsIn nature, lysins are enzymes derived from naturally occurringpotent enzymatic killers of bacteria produced by bacteriophage, which are viruses that infect bacteria. When recombinantly produced from genetic sequences as purified proteins and then applied to bacteria, lysins cleave a key component of the target bacteria’s peptidoglycan cell wall, resulting in rapid bacterial cell death. Conventional antibiotics require bacterial cell division and metabolism to occur in order to exert their effect (i.e., cell death or cessation of growth). Based onin vitro tests, lysins, however, are fundamentally different in that they kill bacteria rapidly by enzymatic cleavage of the bacterial cell wall without need for bacterial growth and cell division. In addition to the speed of action and potent cidality, we believe lysins are differentiated by their other hallmark features which include the demonstrated ability to eradicate biofilms and synergistically boost the efficacy of conventional antibiotics in animal models. Importantly,Naturally occurring lysins alsotargeting gram-positive pathogens have a “narrow spectrum” meaning they kill only specific species of bacteria or closely related bacteria. As such, we believe that lysins targeting gram-positive pathogens willactivity and are not expected to have negative effects on the beneficial, normal human GI microbiome in contrast to conventional “broad spectrum” antibiotics which can kill the body’s normal, beneficial bacteria. We believe that the potential therapeutic profile of lysins is complementary to that of conventional antibiotics. As such, our 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.

We employ bioinformatics and a series of metagenomic-based techniques to identify and clone bacteriophage 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 bacteriophage lysin activity form the major component of our lysin discovery work. Once cloned, our scientists also employ a variety of techniques to further optimize and ‘engineer’ changes to the lysins to introduce specific characteristics which we believe may be favorable for potential therapeutic use.

For the functional metagenomic work that we perform, 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. We can vary both the source of environmental DNA and the way we monitor for desired phenotypes to focus only on environmental populations enriched for bacteriophage lysins that can actively kill a pathogen of interest. We sample 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 scalelarge-scale identification of lysins, enabling the production of lysin banks specific for any particular pathogen. We believe 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 our 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

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in vitro activity against a broad range of resistant pathogens, we believe that amurin peptides have the potential to become a powerful addition to our armamentarium against strains of gram-negative pathogens which have extreme-or pan- drug resistance to all or almost all currently available antibiotics. We plan to further progress agents from our amurin peptide program when adequate funding becomes available.

The focus of our research and discovery efforts is currently 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. We believe that

The U.S. patent system permits the filing of provisional andnon-provisional patent applications. Anon-provisional patent application is examined by the United States Patent and Trademark Office (“USPTO”), and can issue as a patent once the USPTO determines that the claimed invention meets the various standards for patentability. A provisional patent application is not examined or prosecuted, and automatically expires 12 months after its filing date if anon-provisional application is not filed based on the provisional application within that12-month period. Provisional applications are often used, among other things, to establish a priority filing date for the subsequently filednon-provisional patent application. The term of individual patents depends upon the legal term for patents in the countries in which they are filed. In most countries in which we file, the patent

Each license agreement terminates upon the later of (i) the expiration or abandonment of the last licensed patent under the license agreement to expire or become abandoned, or (ii) 10 years after the first commercial sale of the first licensed product. Rockefeller may terminate any license agreement in the event of a breach of such agreement by us or if we challenge the validity or enforceability of the underlying patent rights. We may terminate any license agreement at any time on 60 days’ notice.

Many of our competitors may have significantly greater financial resources and expertise in research and development, manufacturing, preclinical testing, conducting clinical trials, obtaining regulatory approvals and marketing approved medicines than we do. We compete with companies that have products on the market or in development for the same indications as our product candidates. Mergers and acquisitions in the pharmaceutical, biotechnology and diagnostic industries may result in even more resources being concentrated among a smaller number of our competitors. These competitors also compete with us in recruiting and retaining qualified scientific and management personnel and establishing clinical trial sites and patient registration for clinical trials. Smaller or early stageearly-stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large and established companies.

The key competitive factors affecting the success of all of our product candidates, if approved, are likely to be their efficacy, safety, convenience, price and the availability of reimbursement from government and other third-party payors. Our commercial opportunity could be reduced or eliminated if our competitors develop and

advertising, promotion, marketing, post-approval monitoring, and marketingpost-approval reporting of products employingbiologics such as those we are developing. We, along with third-party contractors, will be required to navigate the various preclinical, clinical and commercial approval requirements of the governing regulatory agencies of the countries in which we wish to conduct studies or seek approval or licensure of our researchproduct candidates. The process of obtaining regulatory approvals and intellectual property or that we may license from third parties are subject to extensive governmental regulation in the United Statessubsequent compliance with applicable federal, state, local and in other countries. foreign statutes and regulations require the expenditure of substantial time and financial resources.

U.S. Regulation of Drugs and Biologics

In the United States, ourthe FDA regulates biological products will be regulated as biologics and subject tounder the Federal Food, Drug, and Cosmetic Act as amended (the “FDC Act”(“FDCA”), and the Public Health Service Act as amended (the “PHSA”(“PHSA”), and their implementing regulations, and biologics under the FDCA and the regulationsPublic Health Service Act (“PHSA”), and its implementing regulations. FDA approval is required before any new unapproved drug or dosage form, including a new use of a previously approved drug, can be marketed in the FDA, as well asUnited States. Drugs and biologics are also subject to other federal, state, and local statutes and regulations. These laws, and similar laws outside the United States, govern the research, development, clinical and preclinical testing, manufacture, safety, effectiveness, approval, labeling, distribution, sale, import, export, storage, record-keeping, reporting, advertising, and promotion and marketing of our products. Product development and approval within this regulatory framework, if successful, will require the expenditure of substantial resources and take years to achieve. Violations of regulatory requirements at any stage may result in various adverse consequences, including the FDA’s and other health authorities’ delay in approving or refusal to approve a product and may result in enforcement actions and administrative or judicial sanctions.

The following provides further information on certain legal and regulatory requirements that have the potential to affect our operations and the future marketing of our products.

FDA Approval Process

In the United States, pharmaceutical products are subject to extensive regulationprocess required by the FDA. The FDC Act and other federal and state statutes and regulations govern, among other things, the research, development, testing, manufacture, storage, recordkeeping, approval, labeling, promotion and marketing, distribution, post-approval monitoring and reporting, sampling, and import and export of pharmaceutical products. In addition to

subjects provide their informed consent for their participation in any clinical study. Clinical trials must be conducted: (i) in compliance with federal regulations; (ii) in compliance with good clinical practice (“GCP”) regulations meant to protect the rights and health of healthy volunteers or patients and to define the roles of clinical trial sponsors, administrators, and monitors; as well as (iii)are conducted under protocols detailing, among other things, the objectives of the trial,study, the parameters to be used in monitoring safety and the effectiveness criteria to be evaluated. Each protocol involving testing on healthy volunteers or patients inA separate submission to the U.S.existing IND must be made for each successive clinical trial conducted during product development and for any subsequent protocol amendmentsamendments. While the IND is active, progress reports summarizing the results of the clinical trials and nonclinical studies performed since the last progress report, among other information, must be submitted at least annually to the FDA, and written IND safety reports must be submitted to the FDA as partand investigators for serious and unexpected suspected adverse events, findings from other studies suggesting a significant risk to humans exposed to the drug, findings from animal or in vitro testing suggesting a significant risk to humans exposed to the drug, and any clinically important increased rate of a serious suspected adverse reaction compared to that listed in the IND.protocol or investigator brochure.

The FDAFurthermore, an independent IRB for each site proposing to conduct the clinical trial must review and approve the plan for any clinical trial and its informed consent form before the clinical trial begins at that site, and must monitor the study until completed. Regulatory authorities, the IRB or the sponsor may order the temporary, or permanent, discontinuation ofsuspend a clinical trial at any time on various grounds, including a finding that the subjects are being exposed to an unacceptable health risk or impose other sanctions, if it believes that the trial is unlikely to meet its stated objectives. Some studies also include oversight by an independent group of qualified experts organized by the clinical study sponsor, known as a data safety monitoring board, which provides authorization for whether or not a study may move forward at designated check points based on access to certain data from the study and may halt the clinical trial eitherif it determines that there is not being conducted in accordance with FDA requirements or presents an unacceptable safety risk tofor subjects or other grounds, such as no demonstration of efficacy. There are also requirements governing the clinical trial patients. The study protocolreporting of ongoing preclinical studies and informed consent information for patients in clinical trials must also be submittedand clinical study results to an institutional review board (“IRB”) for approval. An IRB may also require thepublic registries.

The clinical trial at the site to be halted, either temporarily or permanently, for failure to comply with the IRB’s requirements, or may impose other conditions.

Clinical trials to support NDAs or BLAs for marketing approval are typically conducted ininvestigation of a drug is generally divided into three sequential phases, butphases. Although the phases are usually conducted sequentially, they may overlap. In overlap or be combined.

BLA Review Process

Assuming successful completion of all required testing in accordance with all applicable regulatory requirements, the requiredresults of product development, nonclinical studies and clinical testing, an NDA or BLA is prepared andtrials are submitted to the FDA. FDA as part of a BLA requesting approval of the NDA or BLA is required before marketing ofto market the product may begin in the United States.for one or more indications. The NDA or BLA must include theall relevant data available from pertinent preclinical studies and clinical trials, including negative or ambiguous results of all preclinical, clinical, and other testing and a compilation of dataas well as positive findings, together with detailed information relating to the product’s pharmacology, chemistry, manufacture,CMC and controls. The costproposed labeling, among other things. Data can come from company-sponsored clinical studies intended to test the safety and effectiveness of preparingthe product, or from a number of alternative sources, including studies initiated and submitting an NDA or BLA is substantial.sponsored by investigators. The submission of most NDAs and BLAs is additionally subject toa BLA requires payment of a substantial application user fee. For fiscal year 2020,fee to the FDA, unless a waiver or exemption applies.

In addition, under the Pediatric Research Equity Act (“PREA”), a BLA or supplement to a BLA must contain data to assess the safety and effectiveness of the biological product candidate for the claimed indications in all relevant pediatric subpopulations and to support dosing and administration for each pediatric subpopulation for which the product is safe and effective. FDA requires that a sponsor who is planning to submit a marketing application for a drug or biological product that includes a new active ingredient, new indication, new dosage form, new dosing regimen or new route of administration submit an initial pediatric study plan within sixty days after an end-of-Phase 2 meeting or as may be agreed between the sponsor and FDA. Unless otherwise required by regulation, PREA does not apply to any drug or biological product for an indication for which orphan designation has been granted.

Within 60 days following submission of the application, user fee is $2,942,965. The manufacturer and/or sponsor under an approved NDA or BLA are also subject to annual program user fees, currently set at $325,424 per program. These fees are typically adjusted annually.

Thethe FDA has 60 days from its receipt of an NDA orreviews the submitted BLA to determine whetherif the application will be acceptedis substantially complete before the agency accepts it for filing based on the agency’s threshold determinationfiling. The FDA may refuse to file any BLA that it is sufficiently complete to permit substantive review.deems incomplete or not properly reviewable at the time of submission and may request additional information. In this event, the BLA must be resubmitted with the additional information. Once the submission isa BLA has been accepted for filing, the FDA begins anin-depth review. The FDA has agreed to certain performance goals in the review of NDAs and BLAs. The FDA aims to review applications for standard review drugs containing new molecular entities or original biologic products within ten months of the date the application was accepted for filing, and theFDA’s goal is to review standard applications within ten months after the filing date, or, if the application qualifies for priority review, drugs or biologics in six months ofafter the dateFDA accepts the application was accepted for filing. Priority review can be appliedThe FDA reviews a BLA to applications for drugs containing new molecular entitiesdetermine, among other things, whether a product is safe, pure and potent and the facility in which it is manufactured, processed, packed or biologics that are intendedheld meets standards designed to treat a serious disease or conditionassure the product’s continued safety, purity and that, if approved, would provide a significant improvement in safety or effectiveness. The review process forpotency. In both standard and priority reviews, the review process may also be extended by FDA requests for additional information or clarification. When reviewing a BLA, the FDA to consider certain late-submitted information, or information intended to clarify information already provided in the submission.

The FDA may also refer applications for novel drug or biologic products, or drug or biologic products that present difficult questions of safety or efficacy, toconvene an advisory committee—typically a panel that includes clinicians and other experts—forcommittee to provide clinical insight on application review evaluation, and a recommendation as to whether the application should be approved.questions. The FDA is not bound by the recommendationrecommendations of an advisory committee, but it generally followsconsiders such recommendations. recommendations carefully when making decisions.

Before approving a BLA, the FDA will typically inspect the facility or facilities where the product is manufactured. The FDA will not approve an NDA orapplication unless it determines that the manufacturing processes and facilities are in compliance with cGMP requirements and adequate to assure consistent production of the product within required specifications. Additionally, before approving a BLA, the FDA will typically inspect one or more clinical sites to assure compliance with GCP. Additionally, the FDA will inspect the facility or the facilities at which the drug is manufactured. The FDA will not approve the product unless compliance with current good manufacturing practices (“cGMPs”) is satisfactory and the BLA contains data that provide substantial evidence that the proposed biologic is safe, pure and potent for its intended use, and has an acceptable purity profile. In the case of an NDA, whether the drug is safe and effective for its intended use.

After the FDA evaluates the NDA or BLA and theconducts inspections of manufacturing facilities it issues eitherwhere the investigational product and/or its drug substance will be produced, the FDA may issue an approval letter or a complete response letter. A complete response letter generally outlines the deficiencies in the submission and may require substantial additional testing, or information, in order for the FDA to reconsider the application. If, or when, those deficiencies have been addressed to the FDA’s satisfaction in a resubmission of the NDA or BLA, the FDA will issue an approval letter. The FDA has committed to reviewing such resubmissions in two or six months depending on the type of information included.

Complete Response Letter (“CRL”). An approval letter authorizes commercial marketing of the drug or biologicproduct with specific prescribing information for specific indications. As a conditionA CRL will describe all of NDA orthe deficiencies that the FDA has identified in the BLA, except that where the FDA determines that the data supporting the application are inadequate to support approval, the FDA may issue the CRL without first conducting required inspections, testing submitted product lots and/or reviewing proposed labeling. In issuing the CRL, the FDA may recommend actions that the applicant might take to place the BLA in condition for approval, including requests for additional information or clarification. The FDA may delay or refuse approval of a BLA if applicable regulatory criteria are not satisfied, require additional testing or information and/or require post-marketing testing and surveillance to monitor safety or efficacy of a risk evaluationproduct.

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If regulatory approval of a product is granted, such approval will be granted for particular indications and mitigation strategymay entail limitations on the indicated uses for which such product may be marketed. For example, the FDA may approve the BLA with a Risk Evaluation and Mitigation Strategy (“REMS”), to help ensure that the benefits of the drugproduct outweigh its risks. A REMS is a safety strategy to manage a known or biologic outweigh the potential risks. REMS canserious risk associated with a product and to enable patients to have continued access to such medicines by managing their safe use, and could include medication guides, physician communication plans, for healthcare professionals, andor elements to assure safe use, (“ETASU”). ETASU can include, but are not limitedsuch as restricted distribution methods, patient registries and other risk minimization tools. The FDA also may condition approval on, among other things, changes to special trainingproposed labeling or certification for prescribing or dispensing, dispensing only under certain circumstances, special monitoring,the development of adequate controls and

prevalence of the condition and the availability or lack of alternative treatments. In clinical trials,As a surrogate endpoint is a measurementcondition of laboratory or clinical signs of a disease or condition that substitutes for a direct measurement of how a patient feels, functions, or survives. Surrogate endpoints can often be measured more easily or more rapidly than clinical endpoints.

A drug or biologic candidate approved on this basis is subject to rigorous post-marketing compliance requirements, including the completion of Phase 4 or post-approval clinical trials to confirm the effect on the clinical endpoint. Failure to conduct required post-approval studies, or confirm a clinical benefit during post-marketing studies, will allow the FDA to withdraw the drug or biologic from the market on an expedited basis. All promotional materials for drug candidates approved under accelerated regulations are subject to prior review by the FDA.

The Food and Drug Administration Safety and Innovation Act established a category of drugs and biologics referred to as “Breakthrough Therapies” that may be eligible to receive Breakthrough Therapy designation. A sponsor may seek FDA designation of a product candidate as a “Breakthrough Therapy” if the product is intended, alone or in combination with one or more other products, to treat a serious or life-threatening disease or condition and preliminary clinical evidence indicates that the product may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development. Under the Breakthrough Therapy program, the sponsor of a new drug candidate may request that the FDA designate the drug candidate for a specific indication as a breakthrough therapy concurrent with, or after, the filing of the IND for the drug candidate. The designation includes all of the fast track program features, as well as more intensive FDA interaction and guidance. The Breakthrough Therapy designation is a distinct status from both accelerated approval, and priority review, which can also be granted to the same drug if relevant criteria are met. If a product is designated as Breakthrough Therapy, the FDA will workgenerally require the sponsor to expediteperform adequate and well-controlled post-marketing clinical studies to verify and describe the development and review of such drug. The FDAanticipated effect on irreversible morbidity or mortality or other clinical benefit. Products receiving accelerated approval may also rescind Breakthrough Therapy designation for a product candidatebe subject to expedited withdrawal procedures if the FDA determinessponsor fails to conduct the product candidate no longer meetsrequired post-marketing studies or if such studies fail to verify the criteria for Breakthrough Therapy designation.predicted clinical benefit. In February 2020,addition, the FDA granted breakthrough therapy designation to exebacasecurrently requires as a condition for accelerated approval pre-approval of promotional materials, which could adversely impact the treatmenttiming of MRSA bacteremia, including right-sided endocarditis, when used in addition to SOC anti-staphylococcal antibiotics in adult patients.the commercial launch of the product.

Fast track designation, breakthrough therapy designation, priority review, and accelerated approval do not change the standards for approval but may expedite the development or approval process. Even if a product qualifies for one or more of these programs, the FDA may later decide that the product no longer meets the conditions for qualification or decide that the time period for FDA review or approval will not be shortened.

GuidancePost-Approval Requirements

Any products manufactured or distributed pursuant to FDA approvals are subject to pervasive and continuing regulation by the FDA, including, among other things, requirements relating to record-keeping, reporting of adverse experiences, periodic reporting, product sampling and distribution, and advertising and promotion of the product. After approval, most changes to the approved product, such as adding new indications or other labeling claims, are subject to prior FDA review and approval. There also are continuing user fee requirements, under which the FDA assesses an annual program fee for Industry: “Antibacterial Therapieseach product identified in an approved BLA. 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 Patientscompliance with an Unmet Medical Need forcGMPs, which impose certain procedural and documentation requirements upon us and our third-party manufacturers. Changes to the Treatmentmanufacturing process are strictly regulated, and, depending on the significance of Serious Bacterial Diseases” – Potential for Streamlined Developmentthe change, may require prior FDA approval before being implemented. FDA regulations also require investigation and correction of any deviations from cGMPs and impose reporting requirements upon us and any third-party manufacturers that we may decide to use. Accordingly, manufacturers must continue to expend time, money and effort in the area of production and quality control to maintain compliance with cGMPs and other aspects of regulatory compliance.

The FDA issued guidance formay withdraw approval if compliance with regulatory requirements and standards is not maintained or if problems occur after the industryproduct reaches the market. Later discovery of previously unknown problems with a product, including adverse events of unanticipated severity or frequency, or with manufacturing processes, or failure to comply with regulatory requirements, may result in August 2017, whichrevisions to the approved labeling to add new safety information; imposition of post-market studies or clinical studies to assess new safety risks; or imposition of distribution restrictions or other restrictions under a REMS program. Other potential consequences include, among other things:

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The FDA closely regulates the marketing, labeling, advertising and promotion of biologics. A company can make only those claims relating to safety and efficacy, purity and potency that are approved by the FDA and in accordance with the provisions of the approved label. The FDA and other agencies actively enforce the laws and regulations prohibiting the promotion of off-label uses. Failure to comply with these requirements can result in, among other things, discussesadverse publicity, warning letters, corrective advertising and potential civil and criminal penalties. Physicians may prescribe legally available products for uses that are not described in the potentialproduct’s labeling and that differ from those tested by us and approved by the FDA. Such off-label uses are common across medical specialties. Physicians may believe that such off-label uses are the best treatment for antibacterial drug candidates intendedmany patients in varied circumstances. The FDA does not regulate the behavior of physicians in their choice of treatments. The FDA does, however, restrict manufacturer’s communications on the subject of off-label use of their products.

Biosimilars and Reference Product Exclusivity

The Biologics Price Competition and Innovation Act of 2009 (“BPCIA””), created an abbreviated approval pathway for biological products that are highly similar, or “biosimilar,” to treat serious bacterial infectionsor interchangeable with an FDA-approved reference biological product. Biosimilarity, which requires that there be no clinically meaningful differences between the biological product and the reference product in patients who have fewterms of safety, purity, and potency, is generally shown through analytical studies, animal studies, and a clinical study or no available therapiesstudies. Interchangeability requires that a product is biosimilar to the reference product and the product must demonstrate that it can be expected to produce the same clinical results as the reference product in any given patient and, for products that are administered multiple times to an individual, the biologic and the reference biologic may be alternated or switched after one has been previously administered without increasing safety risks or risks of diminished efficacy relative to exclusive use of the reference biologic. A product shown to be candidates for a streamlined development pathway. According to the guidance, candidates for a streamlined process would be likely to have (1) a new mechanism of action that preserves antibacterial activity against bacteria that have mechanisms of resistance to other available antibacterial drugs; (2)biosimilar or interchangeable with an added inhibitor that neutralizes a mechanism of resistance; (3) an alterationFDA-approved reference biological product may rely in the structure of the molecule

health, to prepare or procure products in the event of shortages and critical public health needs, and to authorize the creation and enforcement of regulations to prevent the introduction or spread of communicable diseases in the United States and between states.

After a BLA is approved, the product may also be subject to official lot release as a condition of approval. As part of the manufacturing process, the manufacturer is required to perform certain tests on each lot of the product before it is released for distribution. If the product is subject to official release by the FDA, the manufacturer submits samples of each lot of product to the FDA together with a release protocol showing a summary of the history of manufacture of the lot and the results of all of the manufacturer’s tests performed on the lot. The FDA may also perform certain confirmatory tests on lots of some products, such as viral vaccines, before releasing the lots for distribution by the manufacturer. In addition, the FDA conducts laboratory research related to the regulatory standards on the safety, purity, potency, and effectiveness of biological products. As with drugs, after approval of biologics, manufacturers must address any safety issues that arise, are subject to recalls or a halt in manufacturing, and are subject to periodic inspection after approval.

Biosimilars

The Biologics Price Competition and Innovation Act of 2009 (“BPCIA”), created an abbreviated approval pathway for biological products shown to be highly similar to or interchangeable with anFDA-licensed reference biological product. Biosimilarity sufficient to reference a priorFDA-approved product requires that there be no

resulting from a violation of the U.S. federal Anti-Kickback Statute constitutes a false or fraudulent claim for purposes of the civil False Claims Act. The majority of states also have statutes or regulations similar to the federal anti-kickback law and false claims laws, which apply to items and services reimbursed under Medicaid and other state programs, or, in several states, apply regardless of the payor.

HIPAA also created new federal criminal statutes that prohibit among other actions, knowingly and willfully executing, or attempting to execute, a scheme to defraud any healthcare benefit program, including private third-party payors, knowingly and willfully embezzling or stealing from a healthcare benefit program, willfully obstructing a criminal investigation of a healthcare offense, and knowingly and willfully falsifying, concealing or covering up a material fact or making any materially false, fictitious or fraudulent statement in connection with the delivery of or payment for healthcare benefits, items or services. Similar to the federal Anti-Kickback Statute, a person or entity does not need to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation.

There has also been a recent trend of increased federal and state regulation of payments made to physicians and other healthcare providers. The Patient Protection and Affordable Care Act, as amended by the Health Care and Education Reconciliation Act (collectively, the “Affordable Care Act”“ACA”), among other things, imposes new reporting requirements on drug manufacturers for payments made by them to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors), certain non-physician practitioners (physician assistants, nurse practitioners, clinical nurse specialists, certified nurse anesthetists, anesthesiologist assistants and certified nurse midwives), and teaching hospitals, as well as ownership and investment interests held by physicians and their immediate family members. Failure to submit required information may result in significant civil monetary penalties of up to an aggregate of $165,786 per year (or up to an aggregate of $1,105,241 per yearand additional penalties for “knowing failures”), for all payments, transfers of value or ownership or investment interests that are not timely, accurately and completely reported in an annual submission. Drug manufacturers are required to submit reports to the government by the 90th day of each calendar year. Certain states also mandate implementation of compliance programs, impose restrictions on drug manufacturer marketing practices and/or require the tracking and reporting of gifts, compensation and other remuneration to physicians.

WeViolations of any of the laws described above or any other governmental regulations that apply to us may also be subject to data privacy and security regulation by both the federal government and the statesresult in which we conduct our business. HIPAA, HITECH, and their respective implementing regulations, impose specified requirements relating to the privacy, security and transmission of individually identifiable

the FDA. In addition to new legislation, FDA regulations and policies are often revised or interpreted by the agency in ways that may significantly affect our business and our products. It is impossible to predict whether further legislative changes will be enacted or whether FDA regulations, guidance, policies or interpretations changed or what the effect of such changes, if any, may be.

For example, in December 2016, the 21st Century Cures act, or Cures Act, was signed into law. The Cures Act, among other things, is intended to modernize the regulation of drugs and biologics and spur innovation, but its ultimate implementation remains unclear. Among other things, the Cures Act provides a new “limited population” approval pathway for antibacterial and antifungal drugs intended to treat serious or life-threatening infections.

Government Contracts and Regulation

We currently contract with the federal government. In March 2021, the Company entered into a cost-share contract with BARDA, a division of the U.S. Department of Health and Human Services’ Office of the Assistant Secretary for Preparedness and Response. The base period for the BARDA Contract included government funding of up to $9.8 million to reimburse expenses to support the conduct of the Phase 3 DISRUPT study and futility analysis. In connection with the closure of the trial, the BARDA Contract was modified to provide for up to $6.6 million in funding to support a futility outcome root-cause analysis and the close-out of the Phase 3 DISRUPT study of exebacase. As a government contractor, we are subject to complex and wide-ranging federal and agency-specific regulations and contractual requirements that not only govern how we perform under the contract but also impose other requirements that affect our operations, including socio-economic obligations such as obligations related to affirmative action or maintaining a drug-free workplace. While some of our employees have been involved in government contracts previously, many of these government contracting requirements are new to us as a company. The costs of compliance with these requirements may be significant. Failure to comply with government contracting requirements could result in termination of our contract or the imposition of penalties.

Foreign Regulation

In addition to regulations in the United States, we may becomeare subject to widely varying foreign regulations which may be quite different from those of the FDA, governing, among other things, clinical trials, manufacture, product registration and approval, and pharmaceutical sales. Whether or not FDA approval has been obtained, we must obtain a separate approval for a product by the comparable regulatory authorities of foreign countries prior to the commencement of clinical studies or marketing of the product marketing in these countries. The requirements and process governing the conduct of clinical studies, approval process, variesproduct licensing, pricing and reimbursement vary from country to country,country. Failure to comply with applicable foreign regulatory requirements, may be subject to, among other things, fines, suspension or withdrawal of regulatory approvals, product recalls, seizure of products, operating restrictions and criminal prosecution.

Non-clinical studies and clinical trials

Similar to the United States, the various phases of non-clinical and clinical research in the European Union, or EU, are subject to significant regulatory controls.

Non-clinical (pharmaco-toxicological) studies are performed to demonstrate the health or environmental safety of new chemical or biological substances. Non-clinical studies must be conducted in compliance with the principles of good laboratory practice, or GLP, as set forth in EU Directive 2004/10/EC. In particular, non-clinical studies, both in vitro and in vivo, must be planned, performed, monitored, recorded, reported and archived in accordance with the GLP principles, which define a set of rules and criteria for a quality system for the organizational process and the conditions for non-clinical studies. These GLP standards reflect the Organization for Economic Co-operation and Development requirements.

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Clinical trials of medicinal products in the EU must be conducted in accordance with EU and national regulations and the International Conference on Harmonization (“ICH”) guidelines on GCP as well as the applicable regulatory requirements and the ethical principles that have their origin in the Declaration of Helsinki. If the sponsor of the clinical trial is not established within the EU, it must appoint an EU entity to act as its legal representative. The sponsor must take out a clinical trial insurance policy, and in most EU member states, the sponsor is liable to provide ‘no fault’ compensation to any study subject injured in the clinical trial.

The regulatory landscape related to clinical trials in the EU has been subject to recent changes. The EU Clinical Trials Regulation, or CTR, which was adopted in April 2014 and repeals the EU Clinical Trials Directive, became applicable on January 31, 2022. Unlike directives, the CTR is directly applicable in all EU member states without the need for member states to further implement it into national law. The CTR notably harmonizes the assessment and supervision processes for clinical trials throughout the EU via a Clinical Trials Information System, which contains a centralized EU portal and database.

While the Clinical Trials Directive required a separate clinical trial application, or CTA, to be submitted in each member state in which the clinical trial takes place, to both the competent national health authority and an independent ethics committee, much like the FDA and IRB respectively, the CTR introduces a centralized process and only requires the submission of a single application to all member states concerned. The CTR allows sponsors to make a single submission to both the competent authority and an ethics committee in each member state, leading to a single decision per member state. The CTA must include, among other things, a copy of the trial protocol and an investigational medicinal product dossier containing information about the manufacture and quality of the medicinal product under investigation. The assessment procedure of the CTA has been harmonized as well, including a joint assessment by all member states concerned, and a separate assessment by each member state with respect to specific requirements related to its own territory, including ethics rules. Each member state’s decision is communicated to the sponsor via the centralized EU portal. Once the CTA is approved, clinical study development may proceed.

The CTR foresees a three-year transition period. The extent to which ongoing and new clinical trials will be governed by the CTR varies. Clinical trials for which an application was submitted (i) prior to January 31, 2022 under the Clinical Trials Directive, or (ii) between January 31, 2022 and January 31, 2023 and for which the sponsor has opted for the application of the EU Clinical Trials Directive remain governed by said Directive until January 31, 2025. After this date, all clinical trials (including those which are ongoing) will become subject to the provisions of the CTR.

Medicines used in clinical trials must be manufactured in accordance with Good Manufacturing Practice, or GMP. Other national and EU-wide regulatory requirements may also apply.

Marketing Authorization

In order to market our future product candidates in the EU and many other foreign jurisdictions, we must obtain separate regulatory approvals. More concretely, in the EU, medicinal product candidates can only be commercialized after obtaining a marketing authorization, or MA. To obtain regulatory approval of an investigational medicinal product under EU regulatory systems, we must submit a marketing authorization application, or MAA. The process for doing this depends, among other things, on the nature of the medicinal product. There are two types of MAs:

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Under the centralized procedure, the maximum timeframe for the evaluation of an MAA by the EMA is 210 days. In exceptional cases, the CHMP might perform an accelerated review of an MAA in no more than 150 days (not including clock stops). Innovative products that target an unmet medical need and are expected to be of major public health interest may be longer or shorter thaneligible for a number of expedited development and review programs, such as the Priority Medicines (“PRIME”) scheme, which provides incentives similar to the breakthrough therapy designation in the U.S. PRIME is a voluntary scheme aimed at enhancing the EMA’s support for the development of medicines that requiredtarget unmet medical needs. It is based on increased interaction and early dialogue with companies developing promising medicines, to optimize their product development plans and speed up their evaluation to help them reach patients earlier. Many benefits accrue to sponsors of product candidates with PRIME designation, including but not limited to, early and proactive regulatory dialogue with the EMA, frequent discussions on clinical trial designs and other development program elements, and accelerated MAA assessment once a dossier has been submitted. Importantly, a dedicated contact and rapporteur from the CHMP is appointed early in the PRIME scheme facilitating increased understanding of the product at EMA’s committee level. An initial meeting initiates these relationships and includes a team of multidisciplinary experts at the EMA to provide guidance on the overall development and regulatory strategies.

MAs have an initial duration of five years. After these five years, the authorization may be renewed for FDA approval. In certain countries,an unlimited period on the basis of a reevaluation of the risk-benefit balance.

Data and Marketing Exclusivity

The EU also provides opportunities for market exclusivity. Upon receiving MA, reference products generally receive eight years of data exclusivity and an additional two years of market exclusivity. If granted, data exclusivity prevents regulatory authorities also establish pricingin the EU from referencing the innovator’s data to assess a generic or biosimilar application. During the additional two-year period of market exclusivity, a generic or biosimilar MAA can be submitted, and reimbursement criteria. the innovator’s data may be referenced, but no generic or biosimilar product can be marketed until the expiration of the market exclusivity. The overall ten-year market exclusivity period may be extended to a maximum of eleven years if, during the first eight years a new therapeutic indication with significant clinical benefit over existing therapies is approved. However, there is no guarantee that a product will be considered by the EU’s regulatory authorities to be a new chemical or biological entity, and products may not qualify for data exclusivity.

There is a special regime for biosimilars, or biological medicinal products that are similar to a reference medicinal product but that do not meet the definition of a generic medicinal product, for example, because of

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differences in raw materials or manufacturing processes. For such products, the results of appropriate preclinical or clinical trials must be provided, and guidelines from the EMA detail the type of quantity of supplementary data to be provided for different types of biological product. There are no such guidelines for complex biological products, such as gene or cell therapy medicinal products, and so it is unlikely that biosimilars of those products will currently be approved in the European Union. However, guidance from the EMA states that they will be considered in the future in light of the scientific knowledge and regulatory experience gained at the time.

In addition, under current United States law,the EU, MAAs for new medicinal products have to include the results of studies conducted in the pediatric population, in compliance with a pediatric investigation plan (“PIP”) agreed with the EMA’s Pediatric Committee (“PDCO”). The PIP sets out the timing and measures proposed to generate data to support a pediatric indication of the drug for which MA is being sought. The PDCO can grant a deferral of the obligation to implement some or all of the measures of the PIP until there are restrictions onsufficient data to demonstrate the export of products not approved by the FDA, depending on the country involvedefficacy and the statussafety of the product in adults. Further, the obligation to provide pediatric clinical trial data can be waived by the PDCO when these data is not needed or appropriate because the product is likely to be ineffective or unsafe in children, the disease or condition for which the product is intended occurs only in adult populations, or when the product does not represent a significant therapeutic benefit over existing treatments for pediatric patients. Once the MA is obtained in all the EU member states and study results are included in the product information, even when negative, the product is eligible for six months’ supplementary protection certificate extension (if any is in effect at the time of approval) or, in the case of orphan pharmaceutical products, a two-year extension of the orphan market exclusivity is granted.

Failure to comply with EU and member state laws that country.apply to the conduct of clinical trials, manufacturing approval, MA of medicinal products and marketing of such products, both before and after grant of the MA, manufacturing of pharmaceutical products, statutory health insurance, bribery and anti-corruption or with other applicable regulatory requirements may result in administrative, civil or criminal penalties. These penalties could include delays or refusal to authorize the conduct of clinical trials, or to grant MA, product withdrawals and recalls, product seizures, suspension, withdrawal or variation of the marketing authorization, total or partial suspension of production, distribution, manufacturing or clinical trials, operating restrictions, injunctions, suspension of licenses, fines and criminal penalties. The aforementioned EU rules are generally applicable in the European Economic Area, or EEA, which consists of the 27 EU member states plus Norway, Liechtenstein and Iceland.

Brexit and the Regulatory Framework in the United Kingdom

Since the end of the Brexit transition period on January 1, 2021, Great Britain (England, Scotland and Wales) has not been directly subject to EU laws, however under the terms of the Ireland/Northern Ireland Protocol, EU laws generally apply to Northern Ireland. On February 27, 2023, the United Kingdom (“UK”) Government and the European Commission reached a political agreement on the “Windsor Agreement” which will revise the Protocol on Ireland/Northern Ireland in order to address some of the perceived shortcomings in its operation. Under the proposed changes, Northern Ireland would be reintegrated under the regulatory authority of the Medicines and Healthcare products Regulatory Agency (“MHRA”) with respect to medicinal products. These proposed changes need to be codified and agreed by the respective parliaments of the UK and EU before taking effect.

It is currently unclear to what extent the UK Government will seek to align its regulations with the EU. The EU laws that have been transposed into UK law through secondary legislation remain applicable in Great Britain. However, under the Retained EU Law (Revocation and Reform) Bill 2022, which is currently before the UK parliament, any retained EU law not expressly preserved and “assimilated” into domestic law or extended by ministerial regulations (to no later than June 23, 2026) will automatically expire and be revoked by December 31, 2023. In addition, new legislation such as the (EU) CTR is not applicable in Great Britain. The UK regulatory framework in relation to clinical trials is derived from existing EU legislation (as implemented into UK law, through secondary legislation). On January 17, 2022, the MHRA launched an eight-week consultation on

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