−Removed: We are a biopharmaceutical company focused on the discovery, development, and commercialization of novel antibiotics for serious infectious diseases.
−Removed: We are conducting a Phase 3 clinical program focused on the infectious disease Clostridiodes difficile infection, also known as C.
+Added: We are a biopharmaceutical company focused on the discovery, development, and commercialization of patient-, physician-, caregiver- and societal-friendly medicinal therapies intended to improve quality of life, increase life expectancy, and resolve serious unmet needs.
+Added: Our novel mechanism pipeline of product candidates is designed with the goal to become the patient-friendly, new-era standard-of-care medicines, and to work in harmony with the human microbiome.
+Added: Summit’s lead product candidate, ridinilazole, is a novel first-in-class drug that is engaged in a global Phase III clinical trial program.
+Added: On December 20, 2021, we announced topline results for the Phase III Ri-CoDIFy study evaluating ridinilazole for treating patients suffering from Clostridioides difficile infection, also known as C.
difficile infection, or CDI.
−Removed: We are also expanding our product candidate portfolio through the development of new mechanism, precision antibiotics using our proprietary Discuva Platform.
−Removed: Summit Therapeutics Inc.
−Removed: was incorporated under the laws of the state of Delaware in July 2020, prior to the completion of the Redomiciliation Transaction.
+Added: Our second product candidate, SMT-738, was announced in May 2021 for combating multidrug resistant infections, specifically Carbapenem-resistant Enterobacteriaceae (“CRE”) infections.
+Added: SMT-738 is the first of a novel class of precision antibiotics that has entered into preclinical development.
+Added: We intend to expand our portfolio by developing further new mechanism, new era product offerings that are designed to work in harmony with the human gut microbiome in the therapeutic areas of oncology and infectious diseases.
+Added: Throughout the process of our clinical development of ridinilazole, we have learned a substantial amount regarding the importance of the microbiome as we have sought to reduce C.
+Added: difficile infection recurrence to the lowest practical levels.
+Added: Importantly, as we have continued to intensify our focus on the microbiome, we believe that the focus on the health of the microbiome will become one of the most important developments in human health over the next decade.
+Added: As a result, we intend to implement a strategy that primarily centers on microbiome-focused therapeutics that could benefit treatments in the areas of oncology and anti-infectives.
+Added: We will enact this focus through business development activities, including possible acquisitions of and/or collaborations with existing entities.
+Added: For ridinilazole, we are in the process of evaluating the future path forward, including potential partnership opportunities.
Ridinilazole for Clostridioides difficile Infection
−Removed: Our lead CDI product candidate is ridinilazole (formerly SMT19969), an orally administered small molecule antibiotic.
−Removed: We dosed the first patient in our Phase 3 clinical trials of ridinilazole for CDI in February 2019.
−Removed: The pivotal Phase 3 clinical program consists of two Phase 3 clinical trials that are each designed to assess, as their primary endpoint, the superiority of ridinilazole compared to vancomycin in sustained clinical response, or SCR, which is defined as clinical cure based on the resolution of diarrhea at the end of treatment and no recurrence of CDI within 30 days after the end of treatment.
−Removed: Additional endpoints include safety and tolerability, analyses of the gut microbiome and metabolome, quality of life and health economic outcome measures.
+Added: Our lead CDI product candidate is ridinilazole (formerly SMT19969), an orally administered, novel mechanism, small molecule antibiotic.
+Added: The first patient in our Phase III clinical program was dosed ridinilazole in February 2019.
+Added: The Phase III clinical program consists of two Phase III pivotal clinical trials (“Ri-CoDIFy 1” and “Ri-CoDIFy 2”) which were combined into a single study (“Ri-CoDIFy”).
+Added: The Phase III clinical program also consists of a pediatrics study (“Ri-CoDIFy 3”).
+Added: The Phase III Ri-CoDIFy pivotal trial was designed to assess, as the primary endpoint, the superiority of ridinilazole compared to vancomycin in Sustained Clinical Response (“SCR”), which was defined as Clinical Response of the treated episode of CDI and no recurrence of CDI through 30 days after the end of treatment.
+Added: Additional endpoints included Clinical Response ("CR"), recurrence rate, safety and tolerability, analyses of the gut microbiome and metabolome, in addition to quality of life and health economic outcome measures.
+Added: The top-line results of the Ri-CoDIFy study showed that ridinilazole resulted in a numerically higher SCR rate than vancomycin but did not meet the study’s primary endpoint threshold for superiority.
+Added: Patients treated with ridinilazole, a precision antibiotic, experienced substantially less recurrence of C.
+Added: difficile infection as compared to patients administered vancomycin (nominal p-value = 0.0002).
+Added: It further showed that ridinilazole was well tolerated, and the overall safety profile remained unchanged.
+Added: We are in the process of evaluating the future path forward with respect to ridinilazole, including potential partnership opportunities.
Ridinilazole is designed to selectively target the bacterium Clostridioides difficile (previously known as Clostridium difficile ) or C.
−Removed: difficile , bacteria while preserving the remainder of the gut microbiome, thus allowing more rapid restoration of the microbiome to a healthy state.
+Added: difficile while preserving the commensal microbes of the gut microbiome, thus allowing more rapid restoration of the microbiome to a healthy state.
A healthy, diverse microbiome is associated with decreased CDI recurrence rates.
−Removed: If the Phase 3 program confirms that ridinilazole is associated with decreased recurrence rates and higher SCR rates, these data would potentially have health economic value since CDI recurrence is associated with increased morbidity, mortality, and healthcare costs over weeks to months.
−Removed: The FDA has designated ridinilazole as a qualified infectious disease product, or QIDP, and the FDA granted ridinilazole fast track designation.
−Removed: In 2019, the Centers for Disease Control and Prevention of the U.S.
−Removed: Department of Health and Human Services, or CDC, published an update of its 2013 report reviewing antibiotic resistance threats to the United States.
−Removed: This updated report continued to highlight that CDI poses an immediate public health threat that requires urgent and aggressive action, and is one of four bacterial pathogens with this urgent threat status.
−Removed: CDI is a bacterial infection of the colon that produces toxins causing inflammation of the colon and severe watery diarrhea, painful abdominal cramping, nausea, fever, and dehydration.
+Added: CDI is a bacterial infection of the colon caused by the bacterium C.
+Added: difficile which produces toxins that cause inflammation of the colon resulting in severe watery diarrhea, painful abdominal cramping, nausea, fever, and dehydration.
CDI can also result in more serious disease complications, including bowel perforation, sepsis, and death.
2 unchanged sentences
CDI represents a serious healthcare issue in hospitals, long-term care homes, and in the wider community.
−Removed: In November 2015, we reported top-line results from our double blind, randomized, active controlled Phase 2 clinical trial that evaluated ridinilazole compared to the current standard of care, vancomycin, for the treatment of CDI.
−Removed: The Phase 2 clinical trial exceeded its primary endpoint of non-inferiority, with ridinilazole achieving statistical superiority over vancomycin in SCR.
−Removed: The statistical superiority was driven by a large numerical reduction in recurrent CDI compared with vancomycin.
−Removed: We subsequently reported that data from our Phase 2 clinical trial showed ridinilazole to be highly preserving of the gut microbiome compared to patients who received vancomycin and experienced substantial damage to their gut microbiome that for many patients persisted during the 30-day post-treatment period.
−Removed: Ridinilazole was well tolerated at all doses tested in the Phase 2 clinical trial.
−Removed: We have been awarded a contract from Biomedical Advanced Research and Development Authority, or BARDA, an agency of the U.S.
−Removed: government's Department of Health and Human Services' Office of the Assistant Secretary for Preparedness and Response originally worth up to $62.0 million.
−Removed: In June 2019 and again in January 2020, BARDA increased the value of our contract such that it is now worth up to $72.5 million.
+Added: CDI is the most common healthcare-associated infection.
+Added: Ridinilazole’s Phase III clinical program has been funded in part with federal funds from the Biomedical Advanced Research and Development Authority (“BARDA”), part of the Office of the Assistant Secretary for Preparedness and Response at the U.S.
+Added: Department of Health and Human Services.
+Added: The awarded contract was originally worth up to $62.0 million.
+Added: In June 2019 and again in January 2020, BARDA increased the value of the contract such that it is now worth up to $72.5 million.
+Added: remaining federal government funding is dependent on BARDA at its sole discretion exercising the final independent option work segment, under our achievement of certain agreed-upon milestones for ridinilazole.
As of December 31, 2021, an aggregate of $56.5 million of the total committed BARDA funding has been received.
−Removed: Our contract with BARDA will, in part, fund our ongoing Phase 3 clinical trials and potential regulatory applications for marketing approval for ridinilazole in the United States.
−Removed: We have also entered into a license and commercialization agreement with Eurofarma Laboratórios S.A., or Eurofarma, pursuant to which we granted to Eurofarma exclusive rights to commercialize ridinilazole in specified countries in South America, Central America and the Caribbean.
−Removed: We have retained commercial rights to ridinilazole for the treatment of CDI in the rest of the world.
−Removed: Infectious Disease Pipeline
−Removed: Our goal is to build a franchise in the field of infectious diseases through the discovery and development of new mechanism of action antibiotics focused on treating patients with serious bacterial infections, where there is a substantial unmet need and where we believe we have the ability to show meaningful advantages over current treatments.
−Removed: Our focus is on developing patient friendly antibiotics against pathogens that represent serious healthcare threats.
+Added: We have also entered into a license and commercialization agreement with Eurofarma Laboratórios S.A., or Eurofarma, pursuant to which we granted Eurofarma exclusive rights to commercialize ridinilazole in specified countries in South America, Central America and the Caribbean.
+Added: We have retained commercial rights to ridinilazole for the treatment of CDI across Rest of World territories.
+Added: Other Pipeline Product Candidates
Discuva Platform
−Removed: In December 2017, we expanded our activities in the field of infectious diseases with the acquisition of Discuva Limited, a privately held U.K.-based company.
−Removed: Through this acquisition, we obtained a bacterial genetics software based technology (our Discuva Platform), which facilitates the discovery and development of new mechanism antibiotics.
−Removed: Our Discuva Platform can be used to help elucidate new bacterial targets for drug discovery, understand the mechanism of action of antibiotics and optimize preclinical antibiotic candidates against the propensity to develop bacterial resistance.
−Removed: In addition to discovery project support, the deep biology and microbiology expertise of the Discuva group has been utilized over the past year to gain a better understanding of the mechanism of action of ridinilazole and to characterize the preclinical microbiology of ridinilazole in greater detail.
−Removed: The mechanism of action and microbiology studies will form part of the new drug application, or NDA, filing for ridinilazole.
+Added: In December 2017, we expanded our activities in the field of infectious diseases with the acquisition of Discuva Limited, a privately held United Kingdom-based company.
+Added: Through this acquisition, we obtained a bacterial genetics platform and a suite of software-based technologies (collectively termed our “Discuva Platform”), which facilitate the discovery and development of new mechanism antibiotics.
+Added: Our Discuva Platform can be used to identify new bacterial targets for drug discovery, understand the mechanism of action of small molecules targeting varying types of bacteria and select the most optimal preclinical candidates, including those with the least propensity to develop bacterial resistance.
+Added: In addition to discovery project support, our deep biology and microbiology expertise has been utilized over the past year to provide further insights into the mechanism of action of ridinilazole and to characterize the preclinical microbiology of ridinilazole in greater detail.
+Added: The mechanism of action and microbiology studies may be an important component of any regulatory filings and communications with regulatory agencies for ridinilazole.
Enterobacteriaceae Program
−Removed: We continue to advance our late lead optimization program targeting infections caused by Enterobacteriaceae.
−Removed: We have used our Discuva Platform to identify a novel bacterial target and chemotype for the potential treatment of Enterobacteriaceae infections.
−Removed: Enterobacteriaceae are a family of bacteria responsible for serious infections across a number of conditions including bloodstream infections, urinary tract infections and hospital-acquired pneumonias.
−Removed: Multidrug resistant Enterobacteriaceae are resistant to treatment by most or occasionally all existing antibiotics.
−Removed: The most difficult to treat among them are the Extended Spectrum Beta-Lactamase ("ESBL")-producing and the Carbapenem-Resistant Enterobacteriaceae which according to the CDC, have collectively caused an estimated 210,500 infections and 10,200 deaths in hospitalized patients in the United States in 2017.
−Removed: Our DDS-04 series continues to build on highly promising preclinical in vivo efficacy data with an immediate focus on a new antibiotic agent for the treatment of complex urinary tract infections and associated bacteremia.
−Removed: Neisseria gonorrhoeae program
−Removed: In July 2018, we were granted a sub-award of up to $4.5 million from the Trustees of Boston University under the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator program, or CARB-X, to advance our small molecule antibiotic candidate targeting Neisseria gonorrhoeae (SMT-571).
−Removed: Based on toxicology data from preclinical studies, the SMT-571 chemotype was determined not to have suitable qualities for further development and therefore, we have ceased all work on the gonorrhea program.
+Added: We continue to advance our highly innovative program targeting infections caused by Enterobacteriaceae.
+Added: We have used our Discuva Platform to identify our DDS-04 series, a novel chemotype active against a clinically unexploited bacterial target that has the potential to treat Enterobacteriaceae infections.
+Added: Enterobacteriaceae are a family of bacteria responsible for serious infections across a number of conditions including bloodstream infections, urinary tract infections (“UTI”) and hospital-acquired pneumonias.
+Added: Multi-drug resistant (“MDR”) Enterobacteriaceae are resistant to treatment by most or occasionally all existing antibiotics.
+Added: The most difficult to treat among them are the Extended Spectrum Beta-Lactamase (“ESBL”)-producing and the Carbapenem-resistant Enterobacteriaceae (“CRE”).
+Added: According to the Center for Disease Control and Prevention (“CDC”), ESBL-producing and CRE Enterobacteriaceae have collectively caused an estimated 197,400 infections and 9,100 deaths in hospitalized patients in the United States in 2019.
+Added: Our DDS-04 series continues to build on highly promising preclinical in vivo efficacy data with an immediate focus on a new antibiotic agent for the treatment of complicated urinary tract infections, pneumonia and the associated bacteremia.
+Added: Our lead preclinical candidate for the Enterobacteriaceae program from the DDS-04 series is SMT026738 (formerly “DIS-0104145” and referred to as “SMT-738”).
+Added: SMT-738 is a novel small molecule inhibitor of the essential bacterial lipoprotein transport system (LolCDE) in Gram-negative bacteria, which displays a narrow spectrum of activity towards Enterobacteriaceae.
+Added: SMT-738 has demonstrated potent in vitro activity against global MDR isolates of E.
+Added: pneumoniae, including the clinically challenging NDM-carrying CRE isolates where many currently available treatment options have succumbed to clinical resistance including colistin, an antibiotic of last resort.
+Added: Most importantly, SMT-738 has also shown robust in vivo efficacy in relevant murine models of UTI, pneumonia and sepsis.
+Added: A preliminary rodent toxicity study has been concluded and the data supports the continued clinical development of SMT-738.
+Added: SMT-738 has the potential to become a first in class antibiotic to treat life-threatening infections.
+Added: Summit has received a sub-award from CARB-X to progress SMT-738 through preclinical development and an option to continue into Phase Ia clinical studies.
+Added: The award commits initial non-dilutive funding of up to $4.1 million for the preclinical phase, with the potential for a further $3.7 million available for the continued clinical development upon successfully achieving key preclinical development milestones.
+Added: We have been and plan to continue to perform IND-enabling activities.
Our Product Development Pipeline
The following table summarizes our product development pipeline.
−Removed: We are also developing an earlier stage pipeline of antibiotic compounds for serious bacterial infections.
−Removed: * We have granted Eurofarma an exclusive license to the commercial rights for ridinilazole in specified countries in South America, Central America and the Caribbean.
−Removed: We retain commercialization rights in the rest of the world.
−Removed: Our goal is to become a fully-integrated biopharmaceutical company focused on the discovery, development, and commercialization of novel mechanism of action antibiotics for the treatment of serious infectious diseases.
−Removed: Our most advanced program targets CDI, and we have an emerging pipeline of new mechanism antibiotics.
+Added: (1) We have granted Eurofarma (see further discussion below of funding arrangement) an exclusive license to the commercial rights for ridinilazole in specified countries in South America, Central America and the Caribbean.
+Added: We retain commercialization rights across Rest of World territories.
+Added: (2) Currently supported by funding from CARB-X (see further discussion below of funding arrangement).
+Added: Our goal is to become a fully integrated biopharmaceutical company focused on the discovery, development, and, commercialization of patient-, provider-, novel mechanism of action and/or new era products that work in harmony with the human gut microbiome, including innovative therapeutics for the treatment of certain cancers and infectious diseases.
+Added: We have announced our intention to continue to expand our pipeline with therapeutics that work in conjunction with the human gut microbiome for the treatment of certain cancers and infectious diseases through business development activities including, but not limited to, partnerships with, collaborations with, and/or acquisitions of existing entities.
The key elements of our strategy to achieve this goal are to:
−Removed: Rapidly advance the development of our lead product candidate ridinilazole for the treatment of CDI.
−Removed: We are focusing our resources and business efforts primarily on rapidly advancing the development of ridinilazole for the treatment of CDI.
−Removed: We are currently conducting two global Phase 3 clinical trials that are evaluating the benefits of ridinilazole compared to the current standard of care antibiotic, vancomycin, by testing for superiority in the endpoint of sustained clinical response.
−Removed: Commercialize ridinilazole for CDI in the United States with our own sales team.
−Removed: We hold exclusive commercialization rights for ridinilazole for all indications in the United States.
−Removed: If ridinilazole receives regulatory approval, we intend to commercialize it initially in the United States with our own focused, specialized sales force that we plan to establish.
−Removed: We will evaluate our options to maximize the commercial opportunity for ridinilazole in other key territories where we retain exclusive commercialization rights, including Europe and Asia.
−Removed: We have granted the exclusive right to commercialize ridinilazole in certain countries in South America, Central America, and the Caribbean to Eurofarma in exchange for an upfront payment and specified development, commercial, and sales milestones, as well as specified product supply transfer payments.
−Removed: Expand our product portfolio of new mechanism antibiotics using our Discuva Platform.
−Removed: We are focused on expanding our product portfolio through the identification of new mechanism antibiotics that target pathogens that are classified as posing serious or urgent healthcare threats by organizations such as the CDC and WHO.
−Removed: We are using our proprietary Discuva Platform that includes libraries of a wide range of bacteria to facilitate the discovery and development of our new mechanism antibiotic compounds.
−Removed: For example, we are developing a series of new mechanism antibiotics for the potential treatment of infections caused by highly-resistant Enterobacteriaceae.
−Removed: Maintain and expand our leadership in the field of antibiotic research and development.
−Removed: We are seeking to apply our existing knowledge and experience to position ourselves as a leader in antibiotic research and development and generate a pipeline of new mechanism antibiotics.
−Removed: We aim to design new mechanism, precision antibiotics that are targeted for a pathogen or infection.
−Removed: Precision antibiotics have the potential to preserve the healthy bacteria in the human microbiome that provide natural protection against infection and helps maintain general human health.
−Removed: We may expand our development capabilities or product pipeline through opportunistically in-licensing or acquiring the rights to complementary products, product candidates, or technologies that we believe will enhance our leadership in the field of antibiotic innovation.
−Removed: We believe our strategy will allow us to develop new antibiotics that are able to show meaningful advantages over existing standards of care, which will promote their use in patients and not have them held in reserve.
−Removed: We believe our strategy is aligned with the principles of good antibiotic stewardship.
−Removed: Seek additional governmental and other third-party grants and support.
−Removed: We have obtained development funding and other assistance from government entities, philanthropic, non-government, and not-for-profit organizations for our product candidates.
−Removed: For example, the Wellcome Trust Limited provided funding for ridinilazole up until the completion of our Phase 2 proof of concept clinical trial, and BARDA is providing funding to support our ongoing Phase 3 clinical trials and regulatory development of ridinilazole.
−Removed: We have also received funding from CARB-X and Innovate UK to support the development of previous early-stage programs.
−Removed: We plan to continue to encourage these types of organizations to provide additional funding and support for our development programs.
−Removed: Antimicrobial Resistance
−Removed: Overuse and misuse of antibiotics contribute to two serious public health issues:
−Removed: antimicrobial resistance, or AMR, and CDI.
−Removed: AMR is a natural process that has allowed microbes (bacteria, viruses, fungi and parasites) to survive in their environments for billions of years.
−Removed: As microbes are challenged with antimicrobial substances, some microbes will be able to survive and can pass their AMR genes to the next generation.
−Removed: The overuse and inappropriate use of antimicrobial medicines has increased the rate at which microbes are acquiring AMR, with serious consequences for the effective use of many clinical antibiotics.
−Removed: Approximately 700,000 people die every year from antimicrobial resistant infections.
−Removed: According to the 2016 report, Tackling Drug-Resistant Infections Globally , chaired by Jim O’Neill, the number of deaths due to antimicrobial resistant infections is projected to rise to 10 million by 2050, a number that surpasses deaths due to cancer.
−Removed: The rise of AMR could render once easily treated infections untreatable and undermine the ability of physicians to perform surgeries and other routine medical procedures.
−Removed: From the 1920s through the 1980s, new classes of antibiotics were discovered and approved for use in patients at a pace where AMR was not considered a clinical issue.
−Removed: However, since the 1990s, there has been a dramatic reduction in the number of antibiotics developed with very few new mechanism antibiotics reaching the patient.
−Removed: Consequently, AMR has emerged as an increasingly serious clinical issue.
−Removed: Recently, approved antibiotics have generally been broad-spectrum analogues of older antibiotics already in use.
−Removed: These antibiotics are not necessarily the most appropriate drug for a given infection and resistance has generally developed quickly after their introduction to the clinic.
−Removed: The Pew Trust regularly publishes a pipeline of antibiotics currently in global clinical development, and in March 2021 (the most recent release), the Pew Trust's report showed that of the 41 antibiotics in clinical development, 13 antibiotics are in Phase 3 clinical trials, of which only three are a new class of antibiotic.
−Removed: Antimicrobial Stewardship
−Removed: The CDC defines antimicrobial stewardship as ensuring patients receive the right antibiotic at the right dose, at the right time and for the right duration with the goal of improving patient care, more effectively combating AMR and ultimately saving lives.
−Removed: Our strategy for the development of new antibiotics is closely aligned with good antibiotic stewardship.
−Removed: We believe we can design antibiotics for a specific pathogen or infection, allowing physicians to reserve broad-spectrum antibiotics for idiopathic infections.
−Removed: We believe this approach will serve to improve patient outcomes and reduce resistance development.
+Added: Evaluating the future path forward for our existing pipeline product candidates, including potential partnership opportunities, as applicable.
+Added: For ridinilazole, we are in the process of evaluating the future path forward, including potential partnership opportunities.
+Added: Expand our product portfolio of patient-friendly, new-era standards-of-care through our Summit Therapeutics Innovation Engine, including expanding our pipeline to potentially include patient-friendly oncology treatments.
+Added: We intend to expand our product portfolio through the identification of new-era standards-of-care therapies that work in harmony with the human gut microbiome.
+Added: Our therapeutic areas of focus, incorporating the gut microbiome, include oncology and anti-infectives.
+Added: We intend to expand our pipeline through our Summit Therapeutics Innovation Engine which is our research and discovery capabilities.
+Added: In addition, business development activities are planned to potentially further expand our pipeline through strategic collaborations with, or acquisitions of, target opportunities that elucidate our mission.
Clostridioides difficile Infection Overview
−Removed: Clostridioides difficile , or C.
−Removed: difficile infection ("CDI") is a bacterial infection of the colon that produces toxins causing inflammation of the colon and severe watery diarrhea, painful abdominal cramping, nausea, fever and dehydration.
+Added: Clostridioides difficile infection (“ C.
+Added: difficile infection” or "CDI") is a bacterial infection of the colon caused by the bacterium C.
+Added: difficile which produces toxins that cause inflammation of the colon resulting in severe watery diarrhea, painful abdominal cramping, nausea, fever and dehydration.
CDI can also result in more serious disease complications, including bowel perforation, sepsis and death.
−Removed: CDI represents a serious healthcare issue in hospitals, long-term care homes and in the wider community.
+Added: CDI represents a serious healthcare issue in hospitals as the most common hospital-acquired infection, in long-term care homes and in the wider community.
We estimate that there are approximately half a million cases of CDI each year across the United States based on a meta-analysis published in the Journal of Global Health in June 2019.
5 unchanged sentences
Hypervirulent C.
−Removed: difficile strains have also emerged and are frequently associated with more severe disease.
+Added: difficile strains have also emerged and are frequently associated with more severe diseases.
A paper published in 2018 in the peer-reviewed journal, American Journal of Infection Control , reported that in the United States, the hypervirulent strain, ribotype 027, accounts for approximately one-fifth of all CDI cases.
12 unchanged sentences
Existing treatment options for CDI are limited.
−Removed: Currently, the most commonly used treatments for CDI are vancomycin or off label use of metronidazole, both of which are broad-spectrum antibiotics.
−Removed: Broad-spectrum antibiotics may not be the most appropriate treatment for CDI because although the antibiotics reduce levels of C.
−Removed: difficile , they cause significant collateral damage to the gut microbiome by also killing bacteria that contribute to a healthy microbiome.
+Added: Currently, the most commonly used treatments for CDI is vancomycin, which is a broad-spectrum antibiotic.
+Added: A broad-spectrum antibiotic may not be the most appropriate treatment for CDI because although the antibiotics reduce levels of C.
+Added: difficile , they cause significant collateral damage to the gut microbiome by killing bacteria that contribute to a healthy microbiome.
This collateral damage to the gut microbiome leaves patients vulnerable to recurrent CDI.
−Removed: According to the Infectious Disease Society of America, or IDSA, guidelines, the current standard of care for primary CDI is to treat with antibiotics, such as fidaxomicin or vancomycin.
+Added: According to the Infectious Disease Society of America (“IDSA”) guidelines, the current standard-of-care for primary CDI is to treat with antibiotics, such as fidaxomicin or vancomycin.
Both are recommended to treat primary CDI, and they do not have a label claim to reduce or prevent CDI recurrence.
−Removed: No antibiotic therapeutics are currently approved for treatment of recurrent CDI.
+Added: No antibiotic therapeutics are currently approved for the treatment of recurrent CDI.
In October 2016, the FDA approved bezlotoxumab, a monoclonal antibody, in conjunction with an antibiotic to reduce the recurrence of CDI in patients who have a high risk of recurrence.
+Added: For patients with a recurrent CDI episode within the last 6 months, IDSA suggests using bezlotoxumab as a co-intervention along with standard-of-care (SOC) antibiotics rather than SOC antibiotics alone (conditional recommendation, very low certainty of evidence).
Bezlotoxumab binds to toxin B, one of the toxins produced by the C.
difficile bacteria, to neutralize its effects.
−Removed: Bezlotoxumab does not treat CDI.
+Added: Bezlotoxumab does not treat CDI and has no direct antimicrobial activity.
Ridinilazole for the Treatment of CDI
−Removed: We are developing ridinilazole as an orally administered small molecule antibiotic for the treatment of CDI.
+Added: We have been developing ridinilazole as an orally-administered, small molecule targeted antibiotic for the treatment of CDI.
Ridinilazole is designed to selectively target C.
difficile bacteria while preserving the microbiome and thereby treat the initial infection and reduce CDI recurrence rates.
−Removed: Ridinilazole promotes good stewardship through its targeted spectrum of activity and potential to improve patient outcomes.
−Removed: The active ingredient in ridinilazole is a bis-benzimidazole tetrahydrate.
+Added: Ridinilazole is aligned with good antibiotic stewardship through its targeted spectrum of activity and the potential to reduce disease recurrence.
+Added: Ridinilazole comprises of a symmetrical bis-benzimidazole scaffold which forms its core structure.
We believe, based on preclinical studies conducted to date, that ridinilazole is part of a novel structural class of antibiotics that is distinct from the major classes of marketed antibiotics.
−Removed: We are conducting a Phase 3 clinical program that is evaluating the benefits of ridinilazole compared to the current standard of care antibiotic, vancomycin, in patients with CDI.
−Removed: Our Phase 3 clinical program comprises two randomized, double blind, active controlled, multicenter Phase 3 clinical trials with the primary endpoint in both trials testing for superiority in sustained clinical response, or SCR, which is defined as clinical cure based on the resolution of diarrhea at the end of treatment and no recurrence of CDI within 30 days after the end of treatment.
−Removed: We refer to these two Phase 3 clinical trials as "Ri-CoDIFy 1" and "Ri-CoDIFy 2." We dosed the first patient in our Phase 3 clinical trials in February 2019.
−Removed: As of December 31, 2020, we had enrolled a total of 494 patients into our Phase 3 clinical trials, with a further 866 patients still to be enrolled.
−Removed: We continue to experience a delay in enrollment due to the global COVID-19 pandemic.
−Removed: Due to the uncertainties surrounding COVID-19, we have withdrawn the expected timing of completion for the clinical trials.
−Removed: In November 2015, we reported top-line results from our double blind, randomized, active controlled Phase 2 clinical trial that evaluated ridinilazole compared to the current standard of care, vancomycin, for the treatment of CDI.
−Removed: The Phase 2 clinical trial exceeded its primary endpoint of non-inferiority, with ridinilazole achieving statistical superiority over vancomycin in SCR.
−Removed: The statistical superiority was driven by a large numerical reduction in recurrent CDI compared with vancomycin.
−Removed: We subsequently reported that data from our Phase 2 clinical trial also showed ridinilazole to be highly preserving of the gut microbiome compared to patients who received vancomycin and experienced substantial damage to the gut microbiome, which for many patients persisted during the 30-day post-treatment period.
−Removed: In September 2017, we reported top-line data from our exploratory, open label, active controlled Phase 2 clinical trial evaluating ridinilazole compared to fidaxomicin for the treatment of CDI.
+Added: We conducted a Phase III clinical study that evaluated the benefits of ridinilazole compared to the current standard-of-care antibiotic, vancomycin, in patients with CDI.
+Added: The Phase III Ri-CoDIFy trial had the primary endpoint that was testing for superiority in SCR, which is defined as Clinical Response and no recurrence of CDI within 30 days after the end of treatment.
+Added: Due to the uncertainties surrounding COVID-19 and the desire of Summit to not delay the understanding of potential clinical practice-changing data, Summit combined the two trials, formerly known as “Ri-CoDIFy 1” and "Ri-CoDIFy 2,” into a single study.
+Added: We refer to this Phase III clinical trial as "Ri-CoDIFy." We dosed the first patient in our Phase III clinical trials in February 2019.
+Added: We enrolled 759 patients in the combined Ri-CoDIFy clinical trial.
+Added: On December 20, 2021, we announced topline results for the Phase III Ri-CoDIFy study.
+Added: The study showed that ridinilazole resulted in a numerically higher SCR rate than vancomycin but did not meet the study’s primary endpoint for superiority.
+Added: We will continue to evaluate the underlying data and perform additional analyses, including analyses specific to the microbiome.
+Added: In November 2015, we reported top-line results from our double blind, randomized, active controlled Phase II clinical trial that evaluated ridinilazole compared to the current standard-of-care, vancomycin, for the treatment of CDI.
+Added: The Phase II clinical trial showed its primary endpoint of non-inferiority, with ridinilazole achieving statistical significance in testing the non-inferiority hypothesis to vancomycin in SCR.
+Added: We subsequently reported that data from our Phase II clinical trial also showed ridinilazole to be highly preserving of the gut microbiome and secondary bile acids compared to patients who received vancomycin and experienced substantial damage to the gut microbiome, which for many patients persisted during the 30-day post-treatment period.
+Added: In September 2017, we reported top-line data from our exploratory, open label, active controlled Phase II clinical trial evaluating ridinilazole compared to fidaxomicin for the treatment of CDI.
In the trial, ridinilazole preserved the gut microbiome of CDI patients to a greater extent than fidaxomicin, achieving a key secondary endpoint.
−Removed: Ridinilazole was well tolerated at all doses tested in our completed Phase 1 and Phase 2 clinical trials.
−Removed: We were awarded in September 2017 a contract from BARDA originally worth up to $62.0 million.
−Removed: This contract was increased by BARDA in July 2019 and again in January 2020, and it is now worth up to $72.5 million.
−Removed: As of December 31, 2020, an aggregate of $53.3 million of the total committed BARDA funding has been received.
−Removed: The BARDA contract will, in part, fund our ongoing Phase 3 clinical trials of ridinilazole.
−Removed: We have also received $2.5 million upfront as part of our license and commercialization agreement with Eurofarma Laboratórios S.A., or Eurofarma, pursuant to which we granted to Eurofarma exclusive rights to commercialize ridinilazole in specified countries in South America, Central America and the Caribbean and are eligible to receive additional development milestones upon the achievement of staged patient enrollment targets in our ongoing Phase 3 clinical trials of ridinilazole.
−Removed: In February 2020, we achieved the first of these enrollment targets and triggered a milestone payment of $1.0 million from Eurofarma, and we are eligible to receive up to an additional $2.75 million in development milestones upon the achievement of additional enrollment targets.
−Removed: Under our license and commercialization agreement with Eurofarma, we are also eligible to receive up to $21.4 million in development, commercial and sales milestones when cumulative net sales equal or exceed $100.0 million in the licensed territory.
−Removed: Each subsequent achievement of an additional $100.0 million in cumulative net sales will result in us receiving additional milestone payments, which, when combined with anticipated product supply transfer payments from Eurofarma paid to us in connection with a commercial supply agreement to be entered into between the two parties, will provide payments estimated to range from a mid- to high-teens percentage of cumulative net sales in the licensed territory.
−Removed: We estimate such product supply transfer payments from
−Removed: Eurofarma will range from a high single-digit to low double-digit percentage of cumulative net sales in the licensed territory.
−Removed: We have retained commercial rights to ridinilazole for the treatment of CDI in the rest of the world.
−Removed: The FDA has designated ridinilazole as a qualified infectious disease product, or QIDP.
−Removed: The QIDP incentives are provided through GAIN.
−Removed: The QIDP designation provides for priority review by the FDA, eligibility for “fast track” designation and extension of statutory exclusivity periods in the United States for an additional five years upon FDA approval of the product for the treatment of CDI.
−Removed: The FDA granted fast track designation to ridinilazole in July 2015.
+Added: The overall safety profile of ridinilazole remains unchanged.
Ridinilazole Clinical Development
−Removed: Phase 3 Clinical Trial Program
−Removed: We are currently evaluating ridinilazole in two randomized, double blind, active-controlled, multicenter Phase 3 clinical trials in patients with CDI.
−Removed: We refer to these two Phase 3 clinical trials as "Ri-CoDIFy 1" and "Ri-CoDIFy 2." We are conducting the Phase 3 clinical trials at sites located in the United States, Europe, South America, Central America, Australia, New Zealand, South Korea and Israel.
−Removed: We expect to enroll approximately 680 patients into each of the Phase 3 clinical trials.
−Removed: The first patient was enrolled in February 2019.
−Removed: As of December 31, 2020, we had enrolled a total of 494 patients into both Phase 3 clinical trials.
−Removed: Due to the uncertainties surrounding COVID-19, we are withdrawing the expected timing of completion for the clinical trials.
−Removed: We expect to report quarterly enrollment updates going forward.
−Removed: For further information regarding the uncertainties and impact of the COVID-19 pandemic, see Item 7 'Business Impact of COVID-19 Pandemic'.
−Removed: Quarter Number of Patients Enrolled Cumulative Patients Enrolled
−Removed: Q2 2019 21 30
−Removed: Q3 2019 43 73
−Removed: Q4 2019 78 151
−Removed: Q1 2020 101 252
−Removed: Q2 2020 73 325
−Removed: Q3 2020 64 389
−Removed: Q4 2020 105 494
−Removed: Q1 2021* 103* 597*
−Removed: *Q1 2021 includes quarter-to-date enrollment through March 27, 2021
−Removed: In the trials, we are randomizing patients in a one-to-one ratio to receive either a 200 mg dose of ridinilazole administered twice per day for ten days or a 125 mg dose of vancomycin administered four times per day for ten days.
−Removed: Due to the different treatment regimens, we have also developed dummy placebos that are administered to the patients in the Phase 3 clinical trials according to a schedule designed to maintain the blind within each trial.
−Removed: Enrolled patients must be 18 years of age or older, have a confirmed diagnosis of CDI as measured by the presence of toxin A and/or toxin B of C.
+Added: Phase III Clinical Trial Program
+Added: In the Ri-CoDIFy trial, we randomized patients in a one-to-one ratio to receive either a 200 mg dose of ridinilazole tetrahydrate administered twice per day for ten days or a 125 mg dose of vancomycin administered four times per day for ten days.
+Added: Due to the different treatment regimens, we developed dummy placebos that are administered to the patients in the Phase III clinical trials according to a schedule designed to maintain the blind within each trial.
+Added: Enrolled patients in Ri-CoDIFy were required to be at least 18 years of age or older, have a confirmed diagnosis of CDI as measured by the presence of toxin A and/or toxin B of C.
difficile in the stool as confirmed by a positive free toxin test, and must not have had more than one prior episode of CDI in the previous three months, or more than three episodes in the prior 12 months.
−Removed: Each study in the pivotal phase 3 program is designed to assess, as its primary endpoint, the superiority of ridinilazole compared to vancomycin in sustained clinical response, or SCR, which is defined as clinical cure based on the resolution of diarrhea at the end of treatment and no recurrence of CDI within 30 days after the end of treatment.
−Removed: Additional endpoints include safety and tolerability, analyses of the gut microbiome and metabolome, quality of life and health economic outcome measures.
−Removed: Phase 2 Clinical Trial in Patients with CDI
−Removed: In November 2015, we reported top-line results from our randomized, double blind, active controlled, multicenter, Phase 2 clinical trial of ridinilazole in patients with CDI, and we subsequently presented additional data.
−Removed: We referred to this as our Phase 2 proof of concept clinical trial and as the “CoDIFy’’ study.
+Added: The Ri-CoDIFy Phase III clinical trial was designed to assess, as its primary endpoint, the superiority of ridinilazole compared to vancomycin in Sustained Clinical Response, or SCR, which was defined as Clinical Response of the treated episode of CDI and no recurrence of CDI through 30 days after the end of treatment.
+Added: Additional endpoints included Clinical Response ("CR"), recurrence rate, safety and tolerability, analyses of the gut microbiome and metabolome, in addition to quality of life and health economic outcome measures.
+Added: On December 20, 2021, we announced topline results for the Phase III Ri-CoDIFy study evaluating ridinilazole for the treatment of and Sustained Clinical Response for patients suffering from C.
+Added: difficile infection.
+Added: The study showed that ridinilazole resulted in a numerically higher SCR rate than vancomycin but did not meet the study’s primary endpoint for superiority.
+Added: We will continue to evaluate the underlying data, including analyses specific to the microbiome.
+Added: Phase II Clinical Trial in Patients with CDI
+Added: In November 2015, we reported top-line results from our randomized, double blind, active controlled, multicenter, Phase II clinical trial of ridinilazole in patients with CDI, and we subsequently presented additional data.
+Added: We referred to this as our Phase II proof of concept clinical trial and as the "CoDIFy" study.
We conducted this clinical trial at approximately 35 sites in the United States and Canada.
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We enrolled a total of 100 patients between 18 to 90 years of age.
−Removed: The trial randomized patients in a one-to-one ratio to receive either a 200 mg dose of ridinilazole administered twice per day for ten days or a 125 mg dose of vancomycin administered four times per day for ten days.
+Added: The trial randomized patients in a one-to-one ratio to receive either a 200 mg dose of ridinilazole tetrahydrate administered twice per day for ten days or a 125 mg dose of vancomycin administered four times per day for ten days.
The primary objective of this clinical trial was to evaluate the efficacy of ten days of dosing with ridinilazole compared to treatment with vancomycin.
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Analysis of Results
−Removed: We observed the following results in our Phase 2 proof of concept trial:
−Removed: • Ridinilazole Demonstrated Statistical Superiority Over Vancomycin.
−Removed: Our Phase 2 proof of concept trial met its primary endpoint with ridinilazole achieving a SCR rate of 66.7% compared to 42.4% for vancomycin (non-inferiority margin of 15%, p=0.0004).
−Removed: This represented statistical superiority of ridinilazole over vancomycin using the pre-specified 90% confidence interval.
+Added: We observed the following results in our Phase II proof of concept trial:
+Added: • Ridinilazole Demonstrated Statistical Superiority Over Vancomycin for the Primary Endpoint.
+Added: Our Phase II proof of concept trial met its primary endpoint with ridinilazole achieving a SCR rate of 66.7% compared to 42.4% for vancomycin (non-inferiority margin of 15%, p=0.0004 for testing non-inferiority).
+Added: At the pre-specified 2-sided alpha level of 0.10, ridinilazole was statistically superior to vancomycin.
The primary analysis was conducted on the modified intent-to-treat, or mITT, population (36 patients dosed with ridinilazole, 33 patients dosed with vancomycin) that comprised patients with CDI confirmed by the presence of free toxin in feces.
−Removed: The results of the mITT population were consistent with the intent-to-treat, or ITT, population (50 patients dosed with ridinilazole, 50 patients dosed with vancomycin) and the per protocol, or PP, population (31 patients dosed with ridinilazole, 25 patients dosed with vancomycin).
We also observed a generally consistent trend of improved SCR with ridinilazole across subgroups at higher risk of recurrence, including the elderly, patients who were on concomitant antibiotics at the start of treatment and patients with a prior history of CDI.
• Ridinilazole Demonstrated a Large Reduction in Rates of Recurrence Compared to Vancomycin.
−Removed: We observed that the statistical superiority in SCR with ridinilazole compared to vancomycin was driven by a large numerical reduction in rates of disease recurrence.
−Removed: Clinical cure rates at the end of ten days of treatment were similar, with ridinilazole achieving a rate of 77.8% compared to 69.7% for vancomycin, but ridinilazole achieved a recurrence rate of 14.3% compared to 34.8% for vancomycin during the 30-day post-treatment period.
+Added: We observed that the statistical superiority at 2-sided alpha of 0.10 (which was prespecified in the protocol) in SCR with ridinilazole compared to vancomycin was driven by a large numerical reduction in rates of disease recurrence.
+Added: Clinical cure rates at the end of ten days of treatment were similar, with ridinilazole achieving a rate of 77.8% compared to 69.7% for
+Added: vancomycin, but ridinilazole achieved a recurrence rate of 14.3% compared to 34.8% for vancomycin during the 30-day post-treatment period.
• Ridinilazole had Minimal Impact on the Gut Microbiome.
−Removed: The microbiome primary analysis of the Phase 2 study was performed on fecal samples collected from CDI patients at baseline, and at end of therapy (EOT, Day 10).
+Added: The microbiome primary analysis of the Phase II study was performed on fecal samples collected from CDI patients at baseline, and at end of therapy (EOT, Day 10).
This analysis showed that ridinilazole had minimal impact on the gut microbiome diversity and composition compared to vancomycin indicating a smaller impact on microbiota health and preservation of resistance to infections.
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>1000-fold for Lachnospiraceae and >500-fold for Ruminococcaceae), in the Bacteroidetes (>1000- fold) and in the Actinobacteria (5-fold) phyla.
+Added: These impacts are demonstrated in the illustraiont below.
These reductions were associated with a >20-fold increase in the Proteobacteria and, in particular, a >200-fold increase in Enterobacteriaceae and >1000-fold increase in Klebsiella spp .
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Differential impact of ridinilazole and vancomycin on the gut microbiota
−Removed: Changes in relative abundance of bacterial taxa in CDI patients
−Removed: after 10 day-treatment with ridinilazole or vancomycin
−Removed: lower abundance at the end of treatment Green:
+Added: Changes in relative abundance of bacterial taxa in CDI patients after 10 day-treatment with ridinilazole or vancomycin
+Added: l ower abundance at the end of treatment Green:
higher abundance at the end of treatment
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As expected, in healthy controls, bile acids that can block C.
−Removed: difficile growth, i.e.
−Removed: the protective bile acids were predominant while in Phase 2 CDI patients bile acids that can promote C.
+Added: difficile growth, i.e., the protective bile acids were predominant while in Phase II CDI patients bile acids that can promote C.
difficile growth were predominant.
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Ridinilazole was restricted to the gastrointestinal tract, which is the site where CDI occurs in the body.
−Removed: Systemic exposure was close to or below the level of detection in patients with CDI, with plasma concentrations very similar to those observed in our Phase 1 clinical trial in healthy volunteers.
+Added: Systemic exposure was close to or below the level of detection in patients with CDI, with plasma concentrations very similar to those observed in our Phase I clinical trial in healthy volunteers.
• Ridinilazole Reduced Biomarkers of Inflammation.
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The overall rate of adverse events and serious adverse events reported in the ridinilazole and vancomycin treatment arms were comparable.
−Removed: Phase 2 Exploratory Clinical Trial of Ridinilazole Compared to Fidaxomicin
−Removed: In September 2017, we reported top-line data from our randomized, open label, active controlled, multicenter Phase 2 clinical trial evaluating ridinilazole compared to fidaxomicin for the treatment of CDI.
+Added: Phase II Exploratory Clinical Trial of Ridinilazole Compared to Fidaxomicin
+Added: In September 2017, we reported top-line data from our randomized, open label, active controlled, multicenter Phase II clinical trial evaluating ridinilazole compared to fidaxomicin for the treatment of CDI.
This exploratory clinical trial was designed to generate data comparing ridinilazole to fidaxomicin, a CDI antibiotic launched in 2011, and the results of this clinical trial are expected to help to inform the commercial positioning of ridinilazole.
We conducted this clinical trial at sites in the United Kingdom, Europe and the United States, enrolling 27 patients between 18 and 90 years of age.
−Removed: We randomized patients in a one-to-one ratio to receive either a 200 mg dose of ridinilazole administered twice per day for ten days or a 200 mg dose of fidaxomicin administered twice per day for ten days.
+Added: We randomized patients in a one-to-one ratio to receive either a 200 mg dose of ridinilazole tetrahydrate administered twice per day for ten days or a 200 mg dose of fidaxomicin administered twice per day for ten days.
The trial population was unbalanced with more patients randomized to ridinilazole having predisposing factors for recurrent CDI, and at a higher risk of poorer clinical outcomes as measured by ATLAS score, a tool for evaluating CDI in patients by age, temperature, leukocytes and albumin levels, and use of systemic antibiotics.
−Removed: The primary efficacy objective of this clinical trial was to determine the safety and tolerability of ten days of dosing with 200 mg of ridinilazole compared to dosing with 200 mg of fidaxomicin.
+Added: The primary efficacy objective of this clinical trial was to determine the safety and tolerability of ten days of dosing with 200 mg BID of ridinilazole tetrahydrate compared to dosing with 200 mg BID of fidaxomicin.
The secondary objectives of the clinical trial were to assess the following:
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We believe that these measures provide further evidence of ridinilazole's precision in killing C.
−Removed: difficile while preserving the gut microbiome.
+Added: difficile while preserving the gut.
• Ridinilazole was Well Tolerated.
4 unchanged sentences
The trial was however not designed for efficacy comparisons due to the small number of patients enrolled, and so we believe no conclusions on efficacy should be made based solely on these data.
−Removed: Phase 1 Clinical Trial in Healthy Volunteers
−Removed: In 2013, we completed a randomized, partially blind, placebo controlled Phase 1 clinical trial of ridinilazole in healthy volunteers.
+Added: Phase I Clinical Trial in Healthy Volunteers
+Added: In 2013, we completed a randomized, partially blind, placebo-controlled Phase I clinical trial of ridinilazole in healthy volunteers.
We conducted this clinical trial at a single site in the United Kingdom under approval from the U.K.
52 unchanged sentences
difficile in this study as compared to vancomycin, metronidazole and fidaxomicin.
−Removed: In vitro potency is measured by determining the concentration of a drug (in micrograms per liter) needed to inhibit the growth of 90% of the bacterial strains being
−Removed: tested, referred to as a MIC 90 measurement.
+Added: In vitro potency is measured by determining the concentration of a drug (in micrograms per milliliter) needed to inhibit the growth of 90% of the bacterial strains being tested, referred to as a MIC90 measurement.
A high number, typically higher than 256, indicates a weak antimicrobial effect, and a low number, typically less than eight, indicates a potent antimicrobial effect.
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difficile bacteria while preserving the microbiome and thereby reduce CDI recurrence rates.
−Removed: • Novel Mechansim of Action (MOA) .
−Removed: Ridinilazole is believed to drive its bactericidal effect through a novel MOA that results in lethal perturbation of cell division.
−Removed: Through our Discuva Platform expertise, we are completing studies to confirm the exact MOA to be included in the NDA filing.
Profile of Selectivity of Ridinilazole vs.
Other CDI Antibiotics
+Added: • Novel Mechanism of Action (MOA) .
+Added: Ridinilazole is believed to drive its bactericidal effect through a novel MoA that results in lethal perturbation of cell division.
+Added: We have conducted further studies to characterize the MoA.
+Added: It has now been demonstrated that ridinilizole is able to bind, with high affinity, to the minor groove of double-stranded DNA substrates, including C.
+Added: difficile genomic DNA.
+Added: Cell imaging using fluorescence confocal microscopy has revealed that ridinilazole exclusively co-localizes with genomic DNA in C.
+Added: DNA binding is believed to be the primary mechanism through which ridinilazole exerts its bactericidal activity in C.
+Added: Further studies will be conducted to determine the biological consequences of ridinilazole binding to genomic DNA in C.
• Protection Against CDI Recurrence .
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This is an important finding because a significant portion of CDI patients receive antibiotic treatment for persistent or new infections.
−Removed: Infectious Diseases Pipeline
−Removed: We are seeking to build a pipeline of new, patient friendly antibiotics that focus on treating patients with serious bacterial infections where there remains a substantial unmet need.
−Removed: Our pipeline antibiotic programs are focused on new mechanisms to reset resistance and with microbiome sparing profiles where possible to minimize damage to the human microbiome.
−Removed: In December 2017, we expanded our activities in this field when we acquired Discuva Limited, a privately held U.K.-based company.
−Removed: Through this acquisition, we obtained a complementary bacterial genetics software based technology (the Discuva Platform) that facilitates the discovery and development of new mechanism, precision antibiotics.
−Removed: With this acquisition, we believe we are better placed to advance additional potential drug treatments for patients with serious bacterial infections.
−Removed: We are currently developing a program targeting infections caused by Enterobacteriaceae using our Discuva Platform and the wider antibiotic discovery expertise within the group.
+Added: Other Pipeline Product Candidates
Discuva Platform
4 unchanged sentences
Our pathogen specific transposons have three different activating promoters to drive bacterial gene upregulation, to cause gene disruption, or cause the downregulation of bacterial gene expression.
−Removed: There is normally a single transposon insertion per genome.
+Added: There is a single transposon insertion per genome.
The density of transposon insertion at the different genomic loci is determined in the whole library with insertion rates potentially being as high as every two to three base pairs.
1 unchanged sentence
i) Identifying Essential Genes in Bacteria.
−Removed: We are able to use our Discuva Platform to identify genes within bacteria that are essential for their survival and which we believe will allow us to identify new bacterial targets against which to develop new antibiotic drugs.
+Added: We are able to use our Discuva Platform to identify genes within bacteria
+Added: that are essential for their survival.
+Added: This allows us to identify new bacterial targets against which to develop new
+Added: antibiotic drugs.
ii) Elucidating Mechanism of Action.
−Removed: We are able to use our Discuva Platform to elucidate the mechanism of action of a compound to be inferred by the genes that are upregulated during experiments when in the presence of a drug.
−Removed: We are able to rapidly identify the mechanism of action of a potential drug and this represents an important capability of our Discuva Platform.
−Removed: We have been able to validate the ability of our Discuva Platform to elucidate mechanisms of action by testing antibiotic compounds whose mechanisms of action are known.
+Added: We are able to use our Discuva Platform to elucidate the mechanism of action of
+Added: a compound to be inferred by the genes that are upregulated during experiments when in the presence of a drug.
+Added: are able to rapidly identify the mechanism of action of a potential drug and this represents an important capability of
+Added: our Discuva Platform.
+Added: We have been able to validate the ability of our Discuva Platform to elucidate mechanisms of
+Added: action by testing antibiotic compounds representative of known classes whose mechanisms of action are known.
iii) Understanding Emergent Mechanisms of Resistance.
−Removed: We are able to use our Discuva Platform to test a compound’s susceptibility towards known mechanisms of antibiotic resistance to allow us to select potential drug candidates with what we believe will be much better resistance profiles.
−Removed: We believe the importance of understanding emergent mechanisms of resistance is that it will allow us to discover new antibiotics that have potential for longer use in patients prior to the development of widespread resistance.
+Added: We are able to use our Discuva Platform to test a
+Added: compound’s susceptibility towards known mechanisms of antibiotic resistance to allow us to select potential drug
+Added: candidates with what we believe will be much better resistance profiles.
+Added: We believe the importance of understanding
+Added: patients prior to the development of widespread resistance.
Enterobacteriaceae Program
−Removed: We are developing our DDS-04 series of new mechanism antibiotics for the potential treatment of infections caused by the Enterobacteriaceae, a family of Gram-negative bacteria containing numerous human pathogens such as E.
+Added: We are developing a new mechanism novel small molecule antibiotic (SMT-738 which has originated from our DDS-04 series) for the potential treatment of infections caused by the Enterobacteriaceae, a family of Gram-negative bacteria which includes E.
coli and Klebsiella species.
−Removed: Enterobacteriaceae are responsible for serious infections including bloodstream infections, urinary tract infections and hospital-acquired pneumonias.
−Removed: Multidrug resistant Enterobacteriaceae are resistant to treatment by most or occasionally all of existent antibiotics.
−Removed: The most difficult to treat among them are the ESBL-producing and the Carbapenem-resistant Enterobacteriaceae, which according to the CDC, have collectively caused an estimated 210,500 infections and 10,200 deaths in hospitalized patients in the United States in 2017.
+Added: Enterobacteriaceae are responsible for causing serious infections across multiple indications, for example bloodstream infections, urinary tract infections and hospital-acquired pneumonias.
+Added: Multi-Drug Resistant (“MDR”) Enterobacteriaceae are resistant to treatment by most or occasionally all existing classes of known antibiotics.
+Added: The most difficult to treat infections are those caused by the Extended Spectrum Beta-Lactamase (“ESBL”)-producing Enterobacteriaceae and the Carbapenem-resistant Enterobacteriaceae (“CRE”).
+Added: According to the CDC, ESBL-producing and CRE Enterobacteriaceae have collectively caused an estimated 197,400 infections and 9,100 deaths in hospitalized patients in the United States in 2019.
We identified the novel DDS-04 series using our Discuva Platform and, like ridinilazole, the DDS-04 series has a targeted- spectrum of activity, in this case highly specific for Enterobacteriaceae.
−Removed: Compounds from the series act via a novel and clinically unexploited target, LolCDE, which is involved in the transport of lipoproteins from the inner to outer membrane in Gram-negative bacteria.
+Added: The DDS-04 series act via a clinically unexploited target, LolCDE, which is involved in the transport of lipoproteins from the inner to outer membrane in Gram-negative bacteria.
The cell membrane is crucial for cell viability and the lol genes are essential in bacteria such as E.coli .
−Removed: In April 2019, we reported data that showed our DDS-04 series to be rapidly bactericidal and highly potent across globally diverse Enterobacteriaceae strains, including multi-drug resistant isolates.
−Removed: In July 2019, we reported initial, positive proof of concept data on our DDS-04 series from in vivo models of sepsis, urinary tract infection and pneumonia, with further data presented in September 2019.
−Removed: Our DDS-04 series has also shown a low propensity for resistance development and did not show cross resistance with existing classes of antibiotics in our research studies.
−Removed: Over the past year we have continued to advance the series towards the selection of a preclinical candidate.
−Removed: This includes further in vivo data to demonstrate that selected compounds in the series have the required efficacy in translational urinary tract and sepsis infection models.
−Removed: We continue to believe that our DDS-04 series has the potential to overcome known resistance mechanisms to treat patients with life threatening Enterobacteriaceae infections.
−Removed: Gonorrhoeae program
−Removed: We identified the DDS-01 and DDS-03 series of new mechanism antibiotics targeting Neisseria gonorrhoeae , or N.
−Removed: gonorrhoeae , using our Discuva Platform.
−Removed: In September 2018, we nominated SMT-571 from the DDS-01 series as our preclinical candidate for progression into IND enabling studies.
−Removed: In December 2019, we announced that the focus of our gonorrhea program had moved from SMT-571 to other related compounds from the DDS-01 series as part of the ongoing preclinical studies as we looked to identify and advance an optimal candidate from the DDS-01 series into human clinical trials.
−Removed: IND enabling studies for the DDS-01 series continued in 2020, including preclinical toxicology studies which were performed ahead of downstream first in human studies.
−Removed: These studies did not indicate a satisfactory safety window to merit further development of either individual compounds or the series as a whole.
−Removed: Based on the data from the preclinical studies, both series of antibiotics were determined not to have suitable qualities for further development and therefore, we are ceasing work on the gonorrhea program.
−Removed: In July 2018, we were granted a sub-award of up to $4.5 million from the Trustees of Boston University under the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator program, or CARB-X.
−Removed: CARB-X is a public private partnership dedicated to accelerating antibacterial research and development to address the rising global threat of drug resistant bacteria.
−Removed: In February 2020, CARB-X increased the value of this award by up to $1.2 million, bringing the total value of the award worth up to $5.7 million.
−Removed: However, with our decision not to advance the DDS-01 series of antibiotics and to cease work on the gonorrhea program, we expect CARB-X will cover its remaining share of the work that has been funded under the award.
−Removed: Roche Collaboration
−Removed: Prior to our acquisition of Discuva Limited, in 2014 Roche and Discuva entered into a collaboration using the Discuva Platform for the discovery and development of new antibiotic compounds.
−Removed: The joint research element of the collaboration concluded in early 2018, and Roche is solely responsible for continuing development of any compound that was identified under the collaboration.
−Removed: We are eligible to receive from Roche milestones and royalty payments based on the successful development and commercialization of any such compound.
+Added: In April 2019, we
+Added: reported data that showed our DDS-04 series to be rapidly bactericidal and highly potent across globally diverse Enterobacteriaceae strains, including multi-drug resistant isolates.
+Added: Importantly, our DDS-04 series has a low propensity for resistance development and displays no cross resistance with existing classes of antibiotics.
+Added: In July 2019, we reported initial, positive proof of concept data on an exemplar compound from our DDS-04 series across in vivo rodent models of sepsis, urinary tract infection, and pneumonia with further data presented in September 2019.
+Added: On May 18, 2021, we announced SMT026738 (“SMT-738”) as our preclinical candidate to combat multidrug resistant infections, specifically Carbapenem-resistant Enterobacteriaceae (“CRE”) infections.
+Added: SMT-738 is the first of a novel class of precision antibiotics.
+Added: Combining a novel antibiotic class (SMT-738) with a clinically unexploited target (LolCDE) mitigates the risk of pre-existing resistance, potentially allowing for the effective treatment of infections caused by Enterobacteriaceae that currently have very limited and failing treatment options due to resistance to existing antibiotic classes.
+Added: We retain worldwide clinical development and commercial rights to SMT-738.
+Added: We have been and plan to continue to perform IND-enabling activities.
Our Collaborations and Funding Arrangements
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In January 2020, BARDA increased the contract by a further $8.8 million.
−Removed: This increased the total value of the funding contract to up to $72.5 million and brought the total amount of committed BARDA funding to $62.4 million.
+Added: This increased the total value of the funding contract to $72.5 million and brought the total amount of committed BARDA funding to $62.4 million.
+Added: The remaining federal government funding is dependent on BARDA in its sole discretion exercising the final independent option work segment, upon the achievement by the Company of certain agreed-upon milestones for ridinilazole.
As of December 31, 2021, an aggregate of $56.5 million of the total committed BARDA funding has been received and the Company has recognized $50.3 million of cumulative income since contract inception.
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Under this cost sharing arrangement, we are responsible for a portion of the costs associated with each segment of work, including any costs in excess of the estimated amounts.
−Removed: During the base period of the contract, BARDA agreed to fund, in part, activities for our two Phase 3 clinical trials of ridinilazole, which included obtaining requisite regulatory approvals for the opening of trial sites, arranging for the manufacture of clinical supply of ridinilazole and engaging third-party contract research organizations to conduct the clinical trials including initial patient enrollment and treatment.
+Added: During the base period of the contract, BARDA agreed to fund, in part, activities for our two Phase III clinical trials of ridinilazole, which were later combined into one trial (Ri-CoDIFy), and included obtaining requisite regulatory approvals for the opening of trial sites, arranging for the manufacture of clinical supply of ridinilazole and engaging third-party contract research organizations to conduct the clinical trials including initial patient enrollment and treatment.
Under the original terms of the award, the three option work segments, if exercised in full, provided for up to an additional $30 million of funding from BARDA to support the development of ridinilazole through to potential submission of applications for marketing approval.
1 unchanged sentence
In August 2018, one of the three option work segments was exercised by BARDA with the $12.0 million in funding to be drawn down to specifically support drug manufacturing activities required for the submission of marketing approval applications and other regulatory activities.
−Removed: In June 2019, a second of the three option work segments was exercised by BARDA with the $9.6 million in funding to be drawn down to support patient enrollment and dosing in the ongoing Phase 3 clinical trials of ridinilazole.
+Added: In June 2019, a second of the three option work segments was exercised by BARDA with the $9.6 million in funding to be drawn down to support patient enrollment and dosing in the Phase III clinical trials of ridinilazole.
In January 2020, BARDA increased its award by $8.8 million, with this additional funding to support a new clinical trial in adolescent patients.
1 unchanged sentence
The remaining option work segment is an independent, discrete work segment that is eligible to be exercised, in BARDA’s sole discretion, upon the completion of agreed-upon milestones and deliverables.
−Removed: If this option work segment is exercised by BARDA, the contract would run into 2022, unless extended by us and BARDA.
+Added: If this option work segment is exercised by BARDA, the contract will run through April 2022, unless extended by us and BARDA.
The contract specifies the plan of activities to be conducted under the contract.
18 unchanged sentences
Wellcome Trust
−Removed: In October 2012, we entered into a translation award funding agreement with the Wellcome Trust Limited, as trustee of the Wellcome Trust, in order to support a Phase 1 and a Phase 2 clinical trial of ridinilazole for the treatment of CDI.
+Added: In October 2012, we entered into a translation award funding agreement with the Wellcome Trust Limited, as trustee of the Wellcome Trust, in order to support a Phase I and a Phase II clinical trial of ridinilazole for the treatment of CDI.
We refer to the translation award funding agreement as the translation award agreement.
9 unchanged sentences
Revenue Sharing Agreement
−Removed: The terms of the translation award agreement required us to enter into a revenue sharing agreement with the Wellcome Trust prior to the further development (beyond the Phase 2 trial supported by the 2012 translational award agreement) and commercialization, which together we refer to as the "Exploitation" of any compound or product that is covered by the intellectual property rights created under the translational award agreement or the discovery award agreement, or that is covered by background intellectual property rights.
+Added: The terms of the translation award agreement required us to enter into a revenue sharing agreement with the Wellcome Trust prior to the further development (beyond the Phase II trial supported by the 2012 translational award agreement) and commercialization, which together we refer to as the "Exploitation" of any compound or product that is covered by the intellectual property rights created under the translational award agreement or the discovery award agreement, or that is covered by background intellectual property rights.
Under such revenue sharing agreement, the Wellcome Trust would be entitled to a share of the net revenue that we, our affiliates, licensees or third-party collaborators receive under the Exploitation of the award products or any intellectual property associated with such Exploitation.
9 unchanged sentences
Unless earlier terminated, the revenue sharing agreement will expire upon the later of the expiration of the last patent or patent application covering ridinilazole;
−Removed: the expiration of any agreement or payment obligations entered into by ourselves with a third party relating to the Exploitation of ridinilazole;
+Added: the expiration of any agreement or payment obligations that we have entered into with a third party relating to the Exploitation of ridinilazole;
or the expiration of any payment obligations owed to the Wellcome Trust relating to the Exploitation of ridinilazole.
In addition, each party has the right to terminate the revenue sharing agreement if the other party materially breaches the agreement, and the breach remains uncured for a specified period or the breach is uncurable, or if the other party experiences specified insolvency related events.
−Removed: Discuva Limited Acquisition
−Removed: Share Purchase Agreement
−Removed: In December 2017, we entered into a share purchase agreement with the shareholders of Discuva, a private limited company organized under the laws of England and Wales pursuant to which we acquired all of the outstanding share capital of Discuva.
−Removed: Discuva was a discovery-stage company with a bacterial genetics-based platform that facilitates the discovery and development of new mechanism antibiotics.
−Removed: Under the terms of the share purchase agreement, we paid the Discuva shareholders a total upfront consideration comprised of (A) $6.7 million in cash plus an amount equal to the cash and cash equivalents of Discuva minus (i) indebtedness, (ii) any other liabilities of Discuva at the closing of the transaction that had arisen outside of the ordinary course of business and (iii) funds to be held in escrow and (B) $6.7 million of shares of common stock, satisfied by the issue of 586,685 of our fully-paid shares of common stock at a price per share of $11.41.
−Removed: We made payment of the amount held in escrow, and an additional balancing amount in respect of the closing cash position was made to the Discuva shareholders in December 2018.
−Removed: In addition, the Discuva shareholders will be entitled to receive contingent payments from us based on (i) the receipt of potential research and development tax credits to which Discuva may be entitled for the period from April 1, 2015, to the date of the share purchase agreement and (ii) approximately one-half of the economic benefit from any amounts received in connection with certain payments made to us under an existing collaboration agreement between Discuva and F.
−Removed: Hoffman - La Roche Limited, or Roche.
−Removed: We made two contingent payments to the Discuva shareholders in December 2018 and May 2019 totaling $1.0 million in respect of research and development tax credits for the period from April 2015 to December 2017 (when the acquisition occurred).
−Removed: Separately, certain employees, former employees and former directors of Discuva are eligible for further payments from Discuva of up to $10.6 million based on specified development and clinical milestones related to proprietary product candidates developed under the platform.
−Removed: Under the terms of the share purchase agreement, the Discuva shareholders agreed, subject to certain limited exceptions, to a lock-up period during which they would not sell, transfer or otherwise dispose of, or create any encumbrance over any of, the ordinary shares received as consideration;
−Removed: this lock-up period expired in September 2018.
−Removed: Following the lock-up period, each of the Discuva shareholders agreed for a period of twelve months to only dispose of their ordinary shares in accordance with certain orderly market undertaking provisions specified in the share purchase agreement, which, among other things, limited the number of ordinary shares each seller was permitted to dispose of during such twelve-month period.
−Removed: This orderly market undertaking expired in September 2019.
−Removed: The share purchase agreement also prohibits the selling Discuva shareholders from engaging in certain business activities which are competitive with the business of Discuva at the time of the transaction and from soliciting customers or hiring employees of Discuva, subject to certain limited exceptions as set forth in the agreement, for a period of two years following the date of the agreement.
−Removed: This prohibition expired in December 2019.
−Removed: The share purchase agreement contained customary representations and warranties that we and the selling Discuva shareholders made to each other as of specific dates.
−Removed: The assertions embodied in those representations and warranties were made solely for purposes of the share purchase agreement and may be subject to important qualifications and limitations agreed to by us and the Discuva shareholders in connection with negotiating its terms.
−Removed: Moreover, the representations and warranties may be subject to a contractual standard of materiality that may be different from what may be viewed as material to shareholders or may have been used for the purpose of allocating risk between us and the Discuva shareholders rather than establishing matters as facts.
−Removed: For the foregoing reasons, no person should rely on such representations and warranties as statements of factual information at the time they were made or otherwise.
Eurofarma Laboratórios S.A.
2 unchanged sentences
Financial Terms
−Removed: Under the terms of the license agreement, we received an upfront payment of $2.5 million and are entitled to receive additional development milestones upon the achievement of staged patient enrollment targets in the licensed territory in one of our two ongoing Phase 3 clinical trials of ridinilazole.
−Removed: In February 2020, we achieved the first of these patient enrollment targets to trigger a milestone payment of $1.0 million, and we are eligible to receive up to an additional $2.75 million in development milestones upon the achievement of additional staged enrollment targets.
−Removed: We are also eligible to receive up to $21.4 million in development, commercial and sales milestones when cumulative net sales equal or exceed $100.0 million in the licensed territory.
−Removed: Each subsequent achievement of an additional $100.0 million in cumulative net sales will result in us receiving additional milestone payments, which, when combined with anticipated product supply transfer payments from Eurofarma paid to us in connection with a commercial supply agreement to be entered into between the two parties, will provide payments estimated to range from a mid- to high-teens percentage of cumulative net sales in the licensed territory.
+Added: Under the terms of the license agreement, we received an upfront payment of $2.5 million and are entitled to receive additional development milestones upon the achievement of staged patient enrollment targets in the licensed territory in our Ri-CoDIFy 1 and Ri-CoDIFy 2 Phase III clinical trials for ridinilazole.
+Added: In February 2020, we achieved the first of these patient enrollment targets to trigger a milestone payment of $1.0 million.
+Added: In September 2021, we reached the second enrollment milestone and earned $1.25 million.
+Added: In addition, we could receive an additional $1.5 million in various development milestones.
+Added: We are eligible to receive a further $1.0 million in development milestones, $2.4 million in commercial milestones and up to $18.0 million in sales milestones when cumulative net sales equal or exceed $100.0 million in the Eurofarma licensed territory.
+Added: Each subsequent achievement of an additional $100.0 million in cumulative net sales will result in Summit receiving additional milestone payments, which, when combined with anticipated product supply transfer payments from Eurofarma paid to us in connection with a commercial supply agreement to be entered into between the two parties, will provide payments estimated to range from a mid-teens to high-teens percentage of cumulative net sales in the Eurofarma licensed territory.
We estimate such product supply transfer payments from Eurofarma will range from a high single-digit to low double-digit percentage of cumulative net sales in the licensed territory.
1 unchanged sentence
Under the license agreement, Eurofarma is responsible for all costs related to obtaining regulatory approval of ridinilazole in the licensed territory and is obligated to use commercially reasonable efforts to file applications for regulatory approval in specified countries in the licensed territory within a specified time period after we have filed an application for regulatory approval, or obtained regulatory approval, for ridinilazole in a jurisdiction where we retain commercial rights.
−Removed: To assist Eurofarma in obtaining regulatory approvals in the licensed territory, we are responsible, at our expense, to conduct such additional chemistry, manufacturing and control studies as may be required by regulatory authorities in countries within the licensed territory.
We retain sole responsibility for the clinical development of ridinilazole in all countries and are responsible for all costs related to obtaining regulatory approval for ridinilazole outside of the licensed territory.
We are obligated to use commercially reasonable efforts to supply or cause to be supplied to Eurofarma sufficient commercial supply of ridinilazole, and Eurofarma has agreed to purchase its supply of ridinilazole exclusively from us.
−Removed: If we are unable to supply Eurofarma with commercial supply of ridinilazole during the term of the agreement, we are obligated to transfer to Eurofarma or its third-party suppliers’ know-how that would be needed for Eurofarma or its third-party suppliers to manufacture the product for commercial sale in the licensed territory.
−Removed: Unless earlier terminated, the license and commercialization agreement will expire upon the latest of (i) the earliest date on which there are no longer any valid patent claims covering ridinilazole in the licensed territory, (ii) the earliest date on which there is no longer regulatory exclusivity for ridinilazole in the licensed territory or (iii) ten years from the date of the first commercial sale of ridinilazole in the licensed territory.
−Removed: The license agreement may be terminated by Eurofarma in its entirety upon six months’ prior written notice any time after Eurofarma has paid to us the specified development milestones related to our ongoing Phase 3 clinical trials of ridinilazole.
−Removed: Either party may, subject to a cure period, terminate the license agreement in the event of the other party’s uncured material breach.
−Removed: Eurofarma may also terminate the license agreement under specified circumstances relating to the safety, efficacy or regulatory approvability of ridinilazole or under specified circumstances if Eurofarma determines certain commercialization plans are no longer economically viable.
−Removed: Each of the parties has granted to the other a right of reference to copy and use all information included in any regulatory filing in connection with such other party’s development, manufacture and commercialization, as applicable, of ridinilazole in the territories where such other party retains such rights.
−Removed: In addition, during the term of the license agreement, except in certain limited circumstances, Eurofarma has agreed not to commercialize any competing antibiotic treatments actively marketed for the treatment of CDI in the licensed territory or our territory without our prior written consent.
−Removed: Similarly, we have agreed not to commercialize any antibiotic treatments competing with the licensed products which would be actively marketed for the treatment of CDI in the licensed territory.
−Removed: In July 2018, we were granted a sub-award of up to $4.5 million from the Trustees of Boston University under the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator program, or CARB-X to fund, in part, the development of new mechanism antibiotics for the potential treatment of infections caused by gonorrhea.
+Added: If we are unable to supply Eurofarma with commercial supply of ridinilazole during the term of the agreement, we are obligated to transfer to
+Added: Eurofarma or its third-party suppliers’ know-how that would be needed for Eurofarma or its third-party suppliers to manufacture the product for commercial sale in the licensed territory.
+Added: In July 2018, we were granted a sub-award of up to $4.5 million from the Trustees of Boston University under the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator program (“CARB-X”) to fund, in part, the development of new mechanism antibiotics for the potential treatment of infections caused by gonorrhea.
Under our CARB-X award, we received an initial $2.0 million in funding from CARB-X in July 2018.
1 unchanged sentence
The remaining $2.5 million was split into two option segments.
−Removed: In the third quarter of 2020, we made the decision not to advance the DDS-01 series of antibiotics and to cease work on the gonorrhea program based on toxicology data from preclinical studies.
−Removed: We expect CARB-X will cover its remaining share of the work that has been funded under the award.
−Removed: Sarepta Therapeutics, Inc.
−Removed: In October 2016, we entered into an exclusive license and collaboration agreement with Sarepta, pursuant to which we granted Sarepta the exclusive right to commercialize products in our utrophin modulator pipeline for the treatment of Duchenne muscular dystrophy in certain specified territories in exchange for upfront, development, regulatory and sales milestones, as well as future royalties on product sales.
−Removed: In June 2018, we announced the discontinuation of the development of ezutromid after its Phase 2 clinical trial called PhaseOut DMD did not meet its primary or secondary endpoints.
−Removed: Effective as of August 2019, the agreement with Sarepta was terminated with no material ongoing obligations for either party.
+Added: In the third quarter of 2020, we made the decision not to advance the DDS-01 series of antibiotics and to cease work on the gonorrhoeae program based on toxicology data from preclinical studies.
+Added: Given we have ceased work on the DDS-01 series in 2020, no additional funding has been received by CARB-X in 2021 pursuant to this sub-award.
+Added: In May 2021, we announced the selection of a new preclinical candidate, SMT-738, which originated from the DDS-04 series.
+Added: SMT-738 is being developed to combat multi-drug resistant infections, specifically Carbapenem-resistant Enterobacteriaceae ("CRE") infections.
+Added: Simultaneously, Summit has received a sub-award from CARB-X to progress SMT-738 through preclinical development and an option to continue into Phase Ia clinical studies.
+Added: The award commits initial non-dilutive funding of up to $4.1 million for the preclinical phase, with the potential for a further $3.7 million available for the Phase Ia clinical phase upon successfully achieving key preclinical development milestones.
+Added: As of December 31, 2021, $0.5 million of grant funding from CARB-X has been received, $0.1 million is in accounts receivable for amounts billed, $0.6 million is in other current assets as a contract asset and we have recognized $1.2 million of cumulative income since contract inception.
University College London
2 unchanged sentences
To date, we have paid £0.1 million under this agreement.
+Added: Discuva Limited Acquisition
+Added: Share Purchase Agreement
+Added: In December 2017, we entered into a share purchase agreement with the shareholders of Discuva, a private limited company organized under the laws of England and Wales pursuant to which we acquired all of the outstanding share capital of Discuva.
+Added: Discuva was a discovery-stage company with a bacterial genetics-based platform that facilitates the discovery and development of new mechanism antibiotics.
+Added: Under the terms of the share purchase agreement, we paid the Discuva shareholders a total upfront consideration comprised of (A) $6.7 million in cash plus an amount equal to the cash and cash equivalents of Discuva minus (i) indebtedness, (ii) any other liabilities of Discuva at the closing of the transaction that had arisen outside of the ordinary course of business and (iii) funds to be held in escrow and (B) $6.7 million of shares of common stock, satisfied by the issue of 586,685 of our fully-paid shares of common stock at a price per share of $11.41.
+Added: We made payment of the amount held in escrow, and an additional balancing amount in respect of the closing cash position was made to the Discuva shareholders in December 2018.
+Added: In addition, the Discuva shareholders will be entitled to receive contingent payments from us based on (i) the receipt of potential research and development tax credits to which Discuva may be entitled for the period from April 1, 2015, to the date of the share purchase agreement and (ii) approximately one-half of the economic benefit from any amounts received in connection with certain payments made to us under an existing collaboration agreement between Discuva and F.
+Added: Hoffman - La Roche Limited, or Roche.
+Added: We made two contingent payments to the Discuva shareholders in December 2018 and May 2019 totaling $1.0 million in respect of research and development tax credits for the period from April 2015 to December 2017 (when the acquisition occurred).
+Added: Separately, certain employees, former employees and former directors of Discuva are eligible for further payments from Discuva of up to $10.6 million based on specified development and clinical milestones related to proprietary product candidates developed under the platform.
+Added: The share purchase agreement contained customary representations and warranties that we and the selling Discuva shareholders made to each other as of specific dates.
+Added: The assertions embodied in those representations and warranties were made solely for purposes of the share purchase agreement and may be subject to important qualifications and limitations agreed to by us and the Discuva shareholders in connection with negotiating its terms.
+Added: Moreover, the representations and warranties may be subject to a contractual standard of materiality that may be different from what may be viewed as material to shareholders or may have been
+Added: used for the purpose of allocating risk between us and the Discuva shareholders rather than establishing matters as facts.
+Added: For the foregoing reasons, no person should rely on such representations and warranties as statements of factual information at the time they were made or otherwise.
The biotechnology and pharmaceutical industries are characterized by rapidly advancing technologies, intense competition and a strong emphasis on proprietary products.
18 unchanged sentences
MGB Biopharma Limited is developing MGB-BP-3, a novel antibiotic.
−Removed: In May 2020, top-line results were announced that MGB-BP-3 met endpoints of safety, efficacy and dose selection in an open label, exploratory Phase 2a clinical trial.
+Added: In May 2020, top-line results were announced that MGB-BP-3 met endpoints of safety, efficacy and dose selection in an open label, exploratory Phase IIa clinical trial.
+Added: In January 2021, the company announced a successful end-of-phase II meeting with the FDA, noting the FDA confirmed that the design and the endpoints of their two prospective Phase III studies were appropriate.
+Added: Acurx Pharmaceuticals Inc.
+Added: is developing ibezopolstat, a novel antibiotic.
+Added: In November 2020, top-line results were announced that ibezopolstat met endpoints for efficacy and was reported to be well tolerated with no serious adverse events in an open label, exploratory Phase IIa clinical trial, and ibezopolstat is currently enrolling in a Phase IIb clinical trial.
Other CDI approaches.
6 unchanged sentences
These products would be adjunctive therapy to antibiotics used to treat the episode of CDI.
−Removed: Fecal biotherapy approaches in development include SER-109 and SER-262, which are being developed by Seres Therapeutics Inc., formerly Seres Health, Inc., RBX2660, which was originally being developed by Rebiotix Inc., prior to Rebiotix being acquired by Ferring Pharmaceuticals in April 2018, and CP101, which is being developed by Finch Therapeutics.
−Removed: Seres reported top-line results from a Phase 3 clinical trial of SER-109 in August 2020.
−Removed: The trial met its primary endpoint and Seres expects to meet with the FDA to discuss a potential filing for regulatory approval based on the Phase 3 data.
−Removed: Seres reported results from a Phase 1b clinical trial of SER-262 in patients with CDI in August 2018 and indicated these findings will inform the future development of SER-262.
−Removed: In May 2020, Rebiotix reported positive preliminary results on the primary efficacy measure from one of its two scheduled Phase 3 clinical trials of RBX2660;
−Removed: its second Phase 3 trial is currently enrolling patients.
−Removed: Finch Therapeutics announced positive top-line data from its Phase 2 clinical trial of CP101 related to the reduction of recurrent episodes of CDI.
+Added: Fecal biotherapy approaches in development include SER-109, which is being developed by Seres Therapeutics Inc., formerly Seres Health, Inc., RBX2660, and enema formulation, and RBX7455, an oral formulation, which were originally being developed by Rebiotix Inc., prior to Rebiotix being acquired by Ferring Pharmaceuticals in April 2018, and CP101, which is being developed by Finch Therapeutics.
+Added: Seres reported top-line results from a Phase III clinical trial
+Added: of SER-109 in August 2020.
+Added: The trial met its primary endpoint and Seres expects to meet with the FDA to discuss a potential filing for regulatory approval based on the Phase III data.
+Added: In May 2020, Rebiotix reported positive preliminary results on the primary efficacy measure from one of its two scheduled Phase III clinical trials of RBX2660;
+Added: its second Phase III trial is currently enrolling patients.
+Added: Finch Therapeutics announced positive top-line data from its Phase II clinical trial of CP101 related to the reduction of recurrent episodes of CDI.
Several organizations are exploring compounds for the prevention of CDI.
1 unchanged sentence
difficile bacterial toxins.
−Removed: Pfizer reported positive top-line Phase 2 results in January 2017.
−Removed: Pfizer commenced enrollment into a Phase 3 trial in March 2017;
−Removed: the trial has completed enrollment with results pending.
+Added: Pfizer reported positive top-line Phase II results in January 2017.
+Added: Pfizer entered Phase III testing in 2017, and recently announced results in March 2022.
+Added: The Phase III trial did not meet its pre-specified primary endpoint of prevention of primary CDI, but two secondary endpoints indicate a highly favorable benefit in reducing CDI severity.
Synthetic Biologics, Inc., is developing ribaxamase, an oral enzyme designed to degrade certain IV beta-lactam antibiotics within the GI tract to preserve the natural balance of the microbiome and reduce the risk of colonization by bacteria, including C.
difficile, in order to prevent CDI.
−Removed: In January 2017, it was reported that ribaxamase met its primary endpoint in a Phase 2b clinical trial.
+Added: In January 2017, it was reported that ribaxamase met its primary endpoint in a Phase IIb clinical trial and in November 2018, it announced that it has successfully completed an end-of-Phase II meeting with the FDA to discuss the development of ribaxamase.
+Added: Pursuant to the meeting, the FDA has proposed criteria for Phase III clinical efficacy and safety which, if achieved, may support submission for marketing approval of ribaxamase on the basis of a single Phase III clinical efficacy and safety, which if achieved, may support submission for marketing approval of ribaxamase on the basis of a single Phase III clinical trial.
Da Volterra is developing DAV132, a colon-targeted adsorbent designed to protect the gut microbiome of patients against antibiotic-induced disruption, thus seeking to prevent CDI.
−Removed: DAV132 met its primary endpoint related to safety of DAV132 in a Phase 2 clinical trial, announced in February 2020.
+Added: DAV132 met its primary endpoint related to safety of DAV132 in a Phase II clinical trial, announced in February 2020.
+Added: A Phase III trial has commenced with the first patient randomized in July 2021.
In November 2020 Destiny Pharma acquired global rights to NTCD-M3, a naturally occurring, non-toxigenic strain of C.
1 unchanged sentence
difficile toxins, for the prevention of recurring CDI.
−Removed: Phase 3 studies are planned to start in 2022.
+Added: Phase III studies are planned to start in 2022.
Manufacturing
1 unchanged sentence
We currently rely, and expect to continue to rely, on third parties for the manufacture of our product candidates and any products that we may develop.
−Removed: We currently engage a third-party manufacturer to provide clinical material of the API of ridinilazole with a different supplier responsible for drug product manufacturing services to supply the final drug product for use in the ongoing Phase 3 clinical trials.
+Added: We currently engage a third-party manufacturer to provide clinical material of the API of ridinilazole with a different supplier responsible for drug product manufacturing services that has supplied the final drug product for use in the Phase III clinical program.
We believe these suppliers are suitable for commercial manufacture.
2 unchanged sentences
We obtain the supplies of our product candidates from these manufacturers under master services contracts and specific work orders.
−Removed: However, we do not have long-term supply arrangements in place.
We do not currently have arrangements in place for redundant supply or a second source for API for ridinilazole.
8 unchanged sentences
We also rely on trade secrets, know-how, continuing technological innovation and in-licensing opportunities to develop and maintain our proprietary and competitive position.
−Removed: As of December 31, 2020, we owned or exclusively licensed a total of six U.S.
−Removed: patents, two U.S.
−Removed: patent application, five European patents and two European patent application, including original filings, continuations and divisional applications, as well as numerous other foreign counterparts to these U.S.
+Added: As of December 31, 2021, we owned or exclusively licensed a total of 6 U.S.
+Added: patents, 2 U.S.
+Added: patent applications, 5 European patents and 4 European patent applications, including original filings, continuations and divisional applications, as well as numerous other foreign counterparts to these U.S.
and European patents and patent applications.
−Removed: Our CDI patent portfolio includes the following granted patents and patent applications that we own or exclusively license:
−Removed: • a granted U.S.
−Removed: patent covering the use of ridinilazole in the treatment of CDI, which is scheduled to expire in 2029;
−Removed: • a corresponding granted European patent covering the use of ridinilazole in the treatment of CDI, which is scheduled to expire in 2029;
−Removed: • a granted U.S.
−Removed: patent covering hydrates of ridinilazole, which is scheduled to expire in 2029;
−Removed: • a granted European divisional patent covering hydrates of ridinilazole and pharmaceutical compositions comprising ridinilazole;
−Removed: • a further granted U.S.
−Removed: patent covering the use of ridinilazole in the treatment of CDI, which is scheduled to expire in 2029;
−Removed: • two granted U.S.
−Removed: patents, a granted European patent and a pending, allowed, European divisional application covering second generation agents for the treatment of CDI, which are scheduled to expire in 2031;
−Removed: • a pending International patent application (PCT application) covering polymorphs of ridinilazole and processes for producing ridinilazole.
−Removed: While patent protection is not available for composition of matter claims that only recite the API for ridinilazole, protection may be available for the pharmaceutical compositions comprising ridinilazole as well as other forms thereof such as hydrates (and indeed claims have been secured for the latter in both Europe and the United States).
−Removed: As of December 31, 2020, we owned a total of one U.S.
−Removed: patent and one European patent and a number of pending patent applications, including original filings and continuations, as well as numerous other foreign counterparts to these U.S.
−Removed: and European patents and patent applications, covering the genetics-based technology platform acquired in connection with the Discuva acquisition.
−Removed: We also have a pending patent family covering potential antibiotic and antibacterial compounds identified and developed using our Discuva Platform.
−Removed: This family contains multiple pending national/regional applications in territories including the United States and Europe.
−Removed: The term of individual patents depends upon the legal term for patents in the countries in which they are obtained.
−Removed: In most countries, including the United States, the patent term is 20 years from the filing date of a non-provisional patent application.
−Removed: In the United States, a patent’s term may, in certain cases, be lengthened by patent term adjustment, which compensates a patentee for administrative delays by the U.S.
−Removed: Patent and Trademark Office, or the USPTO, in examining and granting a patent, or may be shortened if a patent is terminally disclaimed over an earlier filed patent.
−Removed: The term of a U.S.
−Removed: patent that covers a drug, biological product or medical device approved pursuant to a pre-market approval, or PMA, may also be eligible for patent term extension when FDA approval is granted, provided that certain statutory and regulatory requirements are met.
−Removed: The length of the patent term extension is related to the length of time the drug is under regulatory review while the patent is in force.
−Removed: The Drug Price Competition and Patent Term Restoration Act of 1984, or the Hatch-Waxman Act, permits a patent term extension of up to five years beyond the expiration date set for the patent.
−Removed: Patent extension cannot extend the remaining term of a patent beyond a total of 14 years from the date of product approval, only one
−Removed: patent applicable to each regulatory review period may be granted an extension and only those claims reading on the approved drug may be extended.
−Removed: Similar provisions are available in Europe such as a supplementary protection certificate, or SPC, an additional form of protection linked to the patent and coming into force after the patent’s expiry.
−Removed: Certain other foreign jurisdictions including Australia, Israel, Japan, Korea, Singapore and Taiwan also have provisions to extend the term of a patent that covers an approved drug, provided that statutory and regulatory requirements are met.
−Removed: Thus, in the future, if and when our product candidates receive approval by the FDA or foreign regulatory authorities, we expect to apply for patent term extensions on issued patents covering those products, depending upon the length of the clinical trials for each drug and other factors.
−Removed: The expiration dates of our patents and patent applications referred to above are without regard to potential patent term extension or other market exclusivity that may be available to us.
−Removed: In addition to patents, we may rely, in some circumstances, on trade secrets to protect our technology and maintain our competitive position.
−Removed: However, trade secrets can be difficult to protect.
−Removed: We seek to protect our proprietary technology and processes, in part, by confidentiality agreements with our employees, corporate and scientific collaborators, consultants, scientific advisors, contractors and other third parties.
−Removed: We also seek to preserve the integrity and confidentiality of our data and trade secrets by maintaining physical security of our premises and physical and electronic security of our information technology systems.
+Added: Our patent portfolio currently contains a total of 80 patents and patent applications.
+Added: Discuva Platform Technology.
+Added: Our Discuva platform technology is currently protected by 12 U.S.
+Added: and foreign patents, and two pending patent applications.
+Added: We expect patent protection for this portfolio to expire in 2032.
+Added: Ridinilazole Program .
+Added: Our ridinilazole program is currently protected by 23 granted U.S.
+Added: and foreign patents, with 3 pending patent applications.
+Added: The patent portfolio directed to ridinilazole includes patents and patent applications directed to composition of matter, polymorphic forms, methods of manufacture and use, and formulation subject matter.
+Added: We expect that our existing patents and patent applications (assuming the applications proceed to grant) will provide patent coverage for our ridinilazole program until 2042.
+Added: SMT-738 Program .
+Added: Our SMT738 program currently has 30 patent applications pending worldwide, directed to the composition of matter.
+Added: We anticipate that our existing portfolio (assuming the applications proceed to grant) will provide patent coverage for our SMT738 program until 2042.
+Added: Patent Term Extension .
+Added: Patent term extensions are available in the U.S.
+Added: and in some foreign countries, to compensate a patentee for patent term lost between patent grant and obtaining marketing approval by a regulatory agency, such as the FDA, for a product that is protected by the patent.
+Added: In accordance with the patent term extension provision of the Drug Price Competition and Patent Term Restoration Act, better known as the “Hatch-Waxman Act”, an extension of time may be granted for one of Summit’s patents protecting ridinilazole, for example, which patent was granted several years before we may obtain marketing approval for the drug product.
+Added: This extension may provide up to an additional five years of patent term.
+Added: Similarly, patent extensions called supplementary protection certificates or “SPCs” may be obtained in some foreign countries for patents granted in advance of obtaining market authorization.
+Added: SPCs may also provide up to an additional five years of patent term.
+Added: Summit will submit applications for patent term extensions in all countries where such extensions are available to extend patent protection for ridinilazole, as well as for future patents granted that are directed to Summit’s other drug programs in development.
+Added: The expiration dates referred to above are without regard to any potential patent term extension or other extension that may be available in the U.S.
+Added: or any other market.
+Added: Pediatric Exclusivity .
+Added: Pediatric exclusivity is another type of marketing exclusivity in the U.S.
+Added: that, if granted, provides for the attachment of an additional six months of marketing protection to the term of any existing regulatory exclusivity, as well as any patent term that is listed in the FDA “Orange Book” for the corresponding drug product.
+Added: This six-month exclusivity may be granted if an NDA sponsor submits pediatric data that fairly respond to a written request from the FDA for such data.
+Added: The data do not need to show the product to be effective in the pediatric population studied;
+Added: rather if the pediatric clinical trial is deemed to fairly respond to the FDA’s request, and reports of the requested pediatric studies are submitted to and accepted by the FDA within the statutory time limits, the additional six months exclusivity is granted.
+Added: A six-month pediatric extension of a SPC may also be obtained in some foreign countries, subject to carrying out an agreed pediatric investigation plan and compliance with other regulatory requirements of that country.
+Added: Trade Secrets .
+Added: In addition to patents, we rely on trade secrets and know-how to develop and maintain our competitive position.
+Added: Trade secrets and know-how can be difficult to protect.
+Added: We seek to protect our proprietary technology and processes, in part, by confidentiality agreements and invention assignment agreements with our employees, consultants, scientific advisors, contractors and commercial partners.
+Added: These agreements are designed to protect our proprietary information and, in the case of the invention assignment agreements, to grant us ownership of technologies that are developed through a relationship with a third-party.
+Added: We also seek to preserve the integrity and confidentiality of our data, trade secrets and know-how by maintaining physical security of our premises and physical and electronic security of our information technology systems.
+Added: Summit is in the process of selecting a name for our ridinilazole product, which we will pursue protection for as a trademark in the U.S.
+Added: and foreign jurisdictions around the world.
+Added: In connection with the development of our product pipeline, we will seek protection for marks we currently use and future marks when appropriate.
+Added: We may not be able to obtain, maintain or protect the intellectual property rights necessary to conduct our business, and we may be subject to claims that we infringe or otherwise violate the intellectual property rights of third parties.
+Added: For more information, please see the section on “Risk Factors – Risks Related to Intellectual Property.”
Clinical Affairs
−Removed: We have robust engagements with nationally and internationally recognized key opinions leaders in research and clinical management of CDI.
+Added: We have robust engagements with nationally and internationally recognized key opinions leaders (“KOLs”) in research and clinical management of CDI.
These KOLs are important in professional societies, peer education, and research and evidence generation, and are assisting us with educational initiatives and clinical development plans.
−Removed: We have a strong publication track record and anticipate multiple presentations at scientific conferences this year to continue to establish ourselves as leaders in C.
+Added: We have a strong publication track record and anticipate multiple presentations at scientific conferences this year to establish ourselves as leaders in C.
difficile and the gut microbiome.
Sales, Marketing and Market Access
−Removed: We expect to commercialize ridinilazole in the United States with our own key commercial functions and a focused, specialty sales force targeting both hospital and community CDI treatment prescribers.
−Removed: We currently have resources focused on global commercial launch readiness planning.
−Removed: We are actively engaging with thought leadership on disease state awareness within the provider, payer, policy and patient advocacy communities.
−Removed: Under the terms of our exclusive license and commercialization agreement with Eurofarma, we have granted Eurofarma the exclusive right to commercialize ridinilazole in certain countries in South America, Central America and the Caribbean.
−Removed: We have retained exclusive commercialization rights in all other territories, including in the United States, Asia and Europe.
−Removed: We will continue to evaluate our options for maximizing the commercial opportunity for ridinilazole outside the United States.
−Removed: We intend to evaluate the relative merits of retaining commercialization rights for ourselves or entering into collaboration arrangements with third parties depending on factors such as the anticipated development costs required to achieve marketing approval, the resources required (human and financial) in each territory in which we receive approval, the relative size of the market opportunity in such territory, the particular expertise of the third party and the proposed financial terms of the arrangement.
−Removed: We plan to build the remainder of our commercial capabilities staged to the progress of our Phase 3 trials.
−Removed: The responsibilities of the current Marketing function includes developing educational initiatives addressing unmet needs within our areas of focus.
−Removed: The Market Access function is assuring federal, state and commercial payer administrative readiness including partnering with Supply Chain on our US distribution and state licensing plan.
+Added: At the present time, we in the process of evaluating the future path forward for our Phase III product candidate, including potential partnership opportunities.
+Added: In light of this, we believe that our current capabilities with respect to building out a commercial team are adequate for ridinilazole and SMT-738.
Government Regulation
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The manufacturing process must be capable of consistently producing quality batches of the candidate product and, among other things, the manufacturer must develop methods for testing the identity, strength, quality and purity of the final product.
−Removed: Additionally, appropriate packaging must be selected and tested and stability studies must be conducted to demonstrate that the candidate product does not undergo unacceptable deterioration over its shelf life.
+Added: Additionally, appropriate packaging must be selected and tested.
+Added: Stability studies must be conducted to demonstrate that the candidate product does not undergo unacceptable deterioration over its shelf-life.
The IND and IRB Processes
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This provision requires drug and biologic companies to make publicly available their policies for expanded access for individual patient access to products intended for serious diseases.
−Removed: Sponsors are required to make such policies publicly available upon the earlier of initiation of a Phase 2 or Phase 3 study;
+Added: Sponsors are required to make such policies publicly available upon the earlier of initiation of a Phase II or Phase III study;
or 15 days after the drug or biologic receives designation as a breakthrough therapy, fast track product, or regenerative medicine advanced therapy.
+Added: Running clinical trials that can support regulatory approvals is the best way to ultimately ensure wide access for patients to our product candidates.
+Added: At this point in the development, we cannot support any use of our product candidates outside of our clinical trials.
In addition, on May 30, 2018, the Right to Try Act, was signed into law.
−Removed: The law, among other things, provides a federal framework for certain patients to access certain investigational new drug products that have completed a Phase 1 clinical trial and that are undergoing investigation for FDA approval.
+Added: The law, among other things, provides a federal framework for certain patients to access certain investigational new drug products that have completed a Phase I clinical trial and that are undergoing investigation for FDA approval.
Under certain circumstances, eligible patients can seek treatment without enrolling in clinical trials and without obtaining FDA permission under the FDA expanded access program.
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and any clinically important increase in the case of a serious suspected adverse reaction over that listed in the protocol or investigator brochure.
−Removed: Phase 1, Phase 2 and Phase 3 clinical trials may not be completed successfully within any specified period, or at all.
+Added: Phase I, Phase II and Phase III clinical trials may not be completed successfully within any specified period, or at all.
Furthermore, the FDA or the sponsor may suspend or terminate a clinical trial at any time on various grounds, including a finding that the research subjects are being exposed to an unacceptable health risk.
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The FDA will typically inspect one or more clinical sites to assure compliance with GCP and the integrity of the clinical data submitted.
−Removed: Concurrent with clinical trials, companies often complete additional animal studies and must also develop additional information about the chemistry and physical characteristics of the drug as well as finalize a process for manufacturing the product in commercial quantities in accordance with cGMP requirements.
−Removed: The manufacturing process must be capable of consistently producing quality batches of the drug candidate and, among other things, must develop methods for testing the identity, strength, quality, purity, and potency of the final drug.
−Removed: Additionally, appropriate packaging must be selected and tested and stability studies must be conducted to demonstrate that the drug candidate does not undergo unacceptable deterioration over its shelf life.
+Added: Concurrent with clinical trials, companies often complete additional animal studies and must also develop additional information about the chemistry and physical characteristics of the drug as well as finalize a process for manufacturing the
+Added: product in commercial quantities in accordance with cGMP requirements.
+Added: The manufacturing process must be capable of consistently producing quality batches of the product candidate and, among other things, must develop methods for testing the identity, strength, quality, purity, and potency of the final drug.
+Added: Additionally, appropriate packaging must be selected and tested and stability studies must be conducted to demonstrate that the product candidate does not undergo unacceptable deterioration over its shelf life.
Under the Pediatric Research Equity Act ("PREA") of 2003, an NDA or supplement thereto must contain data that are adequate to assess the safety and effectiveness of the drug product 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.
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For drugs intended to treat a serious or life-threatening disease or condition, FDA is to provide sponsors with its best judgment on whether pediatric studies would be required and whether their submission would be deferred until after approval.
−Removed: This input is to be given by the FDA at the end-of-phase 1 meeting, for drugs for life-threatening diseases, and at the end-of-phase 2 meeting, for other drugs.
−Removed: A sponsor must submit an initial pediatric study plan, if required under PREA, no later than either 60 calendar days after the date of the end-of-phase 2 meeting or such other time as agreed upon between FDA and the sponsor.
+Added: This input is to be given by the FDA at the end-of-phase I meeting, for drugs for life-threatening diseases, and at the end-of-phase II meeting, for other drugs.
+Added: A sponsor must submit an initial pediatric study plan, if required under PREA, no later than either 60 calendar days after the date of the end-of-phase II meeting or such other time as agreed upon between FDA and the sponsor.
The FDA may, on its own initiative or at the request of the applicant, grant deferrals for submission of some or all pediatric data until after approval of the product for use in adults, or full or partial waivers from the pediatric data requirements.
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Additionally, before approving an NDA, the FDA will typically inspect one or more clinical sites to assure compliance with GCP.
−Removed: Under the FDA Reauthorization Act of 2017, the FDA must implement a protocol to expedite review of responses to inspection reports pertaining to certain applications, including applications for products in shortage or those for which approval is dependent on remediation of conditions identified in the inspection report.
+Added: Under the FDA Reauthorization Act of 2017, the FDA must implement a protocol to expedite review of responses to
+Added: inspection reports pertaining to certain applications, including applications for products in shortage or those for which approval is dependent on remediation of conditions identified in the inspection report.
In addition, as a condition of approval, the FDA may require an applicant to develop a REMS.
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risks they present to the limited number of patients they are intended to treat - specifically, patients who have few or no other treatment options.
−Removed: Drug candidates that qualify for LPAD review may simultaneously qualify for one or more of FDA’s expedited review programs.
+Added: Product candidates that qualify for LPAD review may simultaneously qualify for one or more of FDA’s expedited review programs.
Accelerated Approval Pathway
9 unchanged sentences
The accelerated approval pathway is usually contingent on a sponsor’s agreement to conduct, in a diligent manner, additional post-approval confirmatory studies to verify and describe the drug’s clinical benefit.
−Removed: As a result, a drug 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.
+Added: As a result, a product candidate approved on this basis is subject to rigorous post-marketing compliance requirements, including the completion of Phase IV 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, would allow the FDA to withdraw the drug from the market on an expedited basis.
−Removed: All promotional materials for drug candidates approved under accelerated regulations are subject to prior review by the FDA.
+Added: All promotional materials for product candidates approved under accelerated regulations are subject to prior review by the FDA.
Limited Population Antibacterial Drug Pathway
5 unchanged sentences
The prescribing information must also state that the drug is indicated for use in a limited and specific population of patients and copies of all promotional materials relating to the drug must be submitted to the FDA at least 30 days prior to dissemination of the materials.
−Removed: If the FDA subsequently approves the drug for a broader indication, the agency may remove any post-marketing conditions, including requirements with
−Removed: respect to labeling and review of promotional materials applicable to the product.
+Added: If the FDA subsequently approves the drug for a broader indication, the agency may remove any post-marketing conditions, including requirements with respect to labeling and review of promotional materials applicable to the product.
Nothing in this pathway to approval of a limited population drug prevents sponsors of such products from seeking designation or approval under other provisions of the FDCA, such as accelerated approval.
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Even with submission of this additional information, the FDA ultimately may decide that the application does not satisfy the regulatory criteria for approval.
−Removed: If the FDA approves a product, it may limit the approved indications for use for the product, require that contraindications, warnings or precautions be included in the product labeling, require that post-approval studies, including Phase 4 clinical trials, be conducted to further assess the drug’s safety after approval, require testing and surveillance programs to monitor the product after commercialization, or impose other conditions, including distribution restrictions or other risk management mechanisms, including REMS, which can materially affect the potential market and profitability of the product.
+Added: If the FDA approves a product, it may limit the approved indications for use for the product, require that contraindications, warnings or precautions be included in the product labeling, require that post-approval studies, including Phase IV clinical
+Added: trials, be conducted to further assess the drug’s safety after approval, require testing and surveillance programs to monitor the product after commercialization, or impose other conditions, including distribution restrictions or other risk management mechanisms, including REMS, which can materially affect the potential market and profitability of the product.
The FDA may prevent or limit further marketing of a product based on the results of post-market studies or surveillance programs.
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For example, the FDA may require post-marketing testing, including clinical trials, and surveillance to further assess and monitor the product’s safety and effectiveness after commercialization.
−Removed: In addition, drug manufacturers and other entities involved in the manufacture and distribution of approved drugs are required to register their establishments with the FDA and state agencies, and are subject to periodic unannounced inspections by the FDA and these state agencies for compliance with cGMP requirements.
+Added: In addition, drug manufacturers and other entities involved in the manufacture and distribution of approved drugs are required to register their establishments with the FDA and state agencies.
+Added: The drug manufacturers are subject to periodic unannounced inspections by the FDA and these state agencies for compliance with cGMP requirements.
Changes to the manufacturing process are strictly regulated and often require prior FDA approval before being implemented.
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The FDA strictly regulates the marketing, labeling, advertising and promotion of prescription drug products placed on the market.
−Removed: Regulation includes, among other things, standards and regulations for direct-to-consumer advertising, communications
−Removed: regarding unapproved uses, industry-sponsored scientific and educational activities, and promotional activities involving the Internet and social media.
+Added: Regulation includes, among other things, standards and regulations for direct-to-consumer advertising, communications regarding unapproved uses, industry-sponsored scientific and educational activities, and promotional activities involving the Internet and social media.
Promotional claims about a drug’s safety or effectiveness are prohibited before the drug is approved.
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In addition, the distribution of prescription pharmaceutical products is subject to the Prescription Drug Marketing Act, or PDMA, and its implementing regulations, as well as the Drug Supply Chain Security Act, or DSCSA, which regulate the distribution and tracing of prescription drug samples at the federal level, and set minimum standards for the regulation of distributors by the states.
−Removed: The PDMA, its implementing regulations and state laws limit the distribution of prescription pharmaceutical product samples, and the DSCSA imposes requirements to ensure accountability in distribution and to identify and remove counterfeit and other illegitimate products from the market.
+Added: The PDMA, its implementing regulations and state laws limit the distribution of prescription
+Added: pharmaceutical product samples, and the DSCSA imposes requirements to ensure accountability in distribution and to identify and remove counterfeit and other illegitimate products from the market.
Pediatric Exclusivity
6 unchanged sentences
GAIN Exclusivity for Antibiotics
−Removed: The FDA has designated ridinilazole as a qualified infectious disease product, or QIDP, under the Generating Antibiotic Incentives Now Act, or GAIN Act.
+Added: In July 2015, the FDA has designated ridinilazole as a qualified infectious disease product, or “QIDP”, under the Generating Antibiotic Incentives Now Act, or GAIN Act.
+Added: In 2019, the Centers for Disease Control and Prevention of the U.S.
+Added: Department of Health and Human Services, or CDC, published an update of its 2013 report reviewing antibiotic resistance threats to the United States.
+Added: This updated report continued to highlight that CDI poses an immediate public health threat that requires urgent and aggressive action, and C.
+Added: difficile is one of four bacterial pathogens with this urgent threat status.
Congress passed this legislation to encourage the development of antibacterial and antifungal drug products that treat pathogens that cause serious and life-threatening infections.
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The time required to obtain approval in other countries and jurisdictions might differ from and be longer than that required to obtain FDA approval.
−Removed: Regulatory approval in one country or jurisdiction does not ensure regulatory approval in another, but a failure or delay in obtaining regulatory approval in one country or jurisdiction may negatively impact the regulatory process in others.
+Added: Regulatory approval in one country or jurisdiction does not ensure
+Added: regulatory approval in another, but a failure or delay in obtaining regulatory approval in one country or jurisdiction may negatively impact the regulatory process in others.
Regulation and Marketing Authorization in the European Union
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Member States govern the system for the approval of clinical trials in the European Union.
−Removed: Under this system, an applicant must obtain prior approval from the competent national authority of the E.U.
+Added: Under this system, an applicant must obtain prior approval from the competent national authority of the
Member States in which the clinical trial is to be conducted.
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The website indicated that the audit was expected to commence in December 2020.
−Removed: The European Medicines Agency has announced that the implementation date of the EU Regulation governing CTR and the go-live of the centralized portal is scheduled for December 2021.
+Added: The European Commission published a notice in the Official Journal of the European Union on July 31, 2021 confirming January 31, 2022 as the date of entry into application of the Clinical Trials Regulation and the go-live of its Clinical Trials Information System (“CTIS”).
As in the United States, similar requirements for posting clinical trial information are present in the European Union (EudraCT) website:
https://eudract.ema.europa.eu/ and other countries.
−Removed: PRIME Designation in the European Union
−Removed: In March 2016, the European Medicines Agency, or EMA, launched an initiative to facilitate development of product candidates in indications, often rare, for which few or no therapies currently exist.
−Removed: The PRIority MEdicines, or PRIME, scheme is intended to encourage drug development in areas of unmet medical need and provides accelerated assessment of products representing substantial innovation reviewed under the centralized procedure.
−Removed: Products from small- and medium-sized enterprises, or SMEs, may qualify for earlier entry into the PRIME scheme than larger companies.
−Removed: 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 marketing authorization application assessment once a dossier has been submitted.
−Removed: Importantly, a dedicated Agency contact and rapporteur from the Committee for Human Medicinal Products ('CHMP') or Committee for Advanced Therapies ('CAT') are appointed early in the PRIME scheme facilitating increased understanding of the product at EMA’s Committee level.
−Removed: A kick-off meeting initiates these relationships and includes a team of multidisciplinary experts at the EMA to provide guidance on the overall development and regulatory strategies.
Marketing Authorization
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Regulation (EC) No 1901/2006 provides that prior to obtaining a marketing authorization in the European Union, applicants have to demonstrate compliance with all measures included in an EMA-approved Paediatric Investigation Plan, or PIP, covering all subsets of the pediatric population, unless the EMA has granted (1) a product-specific waiver, (2) a class waiver or (3) a deferral for one or more of the measures included in the PIP.
−Removed: The centralized procedure provides for the grant of a single marketing authorization by the European Commission that is valid across the European Economic Area (i.e.
−Removed: the European Union as well as Iceland, Liechtenstein and Norway).
+Added: The centralized procedure provides for the grant of a single marketing authorization by the European Commission that is valid across the European Economic Area (i.e., the European Union as well as Iceland, Liechtenstein and Norway).
Pursuant to Regulation (EC) No 726/2004, the centralized procedure is compulsory for specific products, including for medicines produced by certain biotechnological processes, products designated as orphan medicinal products, ATMPs and products with a new active substance indicated for the treatment of certain diseases, including products for the treatment of cancer.
For products with a new active substance indicated for the treatment of other diseases and products that are highly innovative or for which a centralized process is in the interest of patients, the centralized procedure may be optional.
−Removed: The centralized procedure may at the request of the applicant also be used in certain other cases.
+Added: The centralized procedure may at the
+Added: request of the applicant also be used in certain other cases.
We anticipate that the centralized procedure will be mandatory for the product candidates we are developing.
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Member State in which the product is to be marketed.
−Removed: This application is identical to the application that would be submitted to the EMA for authorization through the centralized procedure.
+Added: This application is identical to the application that would be submitted to the EMA for authorization through the
+Added: centralized procedure.
The referenced E.U.
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The European Commission or the competent authorities of the E.U.
−Removed: Member States may decide, on justified grounds relating to pharmacovigilance, to proceed with one further five-year period of marketing authorization.
+Added: Member States decide on justified grounds relating to pharmacovigilance, to proceed with one further five-year period of marketing authorization.
Once subsequently definitively renewed, the marketing authorization shall be valid for an unlimited period.
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State and foreign laws also govern the privacy and security of health information in some circumstances, many of which differ from each other in significant ways and often are not preempted by HIPAA, thus complicating compliance efforts.
−Removed: Pharmaceutical Insurance Coverage and Health Care Reform
+Added: Pharmaceutical Coverage and Reimbursement
In the United States and markets in other countries, patients who are prescribed treatments for their conditions and providers performing the prescribed services generally rely on third-party payors to reimburse all or part of the associated healthcare costs.
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• expanded the types of entities eligible for the 340B drug discount program;
−Removed: • established the Medicare Part D coverage gap discount program by requiring manufacturers to provide a 50% (and 70% as of January 1, 2019) point-of-sale-discount off the negotiated price of applicable brand drugs to eligible beneficiaries during their coverage gap period as a condition for the manufacturers’ outpatient drugs to be covered under Medicare Part D;
+Added: • established the Medicare Part D coverage gap discount program by requiring manufacturers to provide a 70% as of January 1, 2019 point-of-sale-discount off the negotiated price of applicable brand drugs to eligible
+Added: beneficiaries during their coverage gap period as a condition for the manufacturers’ outpatient drugs to be covered under Medicare Part D;
• a new Patient-Centered Outcomes Research Institute to oversee, identify priorities in, and conduct comparative clinical effectiveness research, along with funding for such research.
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In January 2013, President Obama signed into law the American Taxpayer Relief Act of 2012, which, among other things, further reduced Medicare payments to several providers, including hospitals, imaging centers and cancer treatment centers, and increased the statute of limitations period for the government to recover overpayments to providers from three to five years.
−Removed: Since enactment of the ACA, there have been, and continue to be, numerous legal challenges and Congressional actions to repeal and replace provisions of the law.
−Removed: For example, with enactment of the Tax Cuts and Jobs Act of 2017, which was signed by President Trump on December 22, 2017, Congress repealed the “individual mandate.” The repeal of this provision, which requires most Americans to carry a minimal level of health insurance, became effective in 2019.
−Removed: Additionally, the 2020 federal spending package permanently eliminated, effective January 1, 2020, the ACA-mandated “Cadillac” tax on high-cost employer-sponsored health coverage and medical device tax and, effective January 1, 2021, also eliminates the health insurer tax.
−Removed: Further, the Bipartisan Budget Act of 2018, among other things, amended the ACA, effective January 1, 2019, to increase from 50 percent to 70 percent the point-of-sale discount that is owed by pharmaceutical manufacturers who participate in Medicare Part D and to close the coverage gap in most Medicare drug plans, commonly referred to as the “donut hole.” We are using this new rate in our gross-to-net forecasts.
−Removed: Should the new Administration seek to expand the scope of the ACA, we expect that new eligible beneficiaries will be subject to significant cost-sharing in return for coverage.
−Removed: We are active in proposing to HHS and CMS that QIDP drugs FDA approved for CDC Urgent Threats be supported for use by waiving patient out-of-pocket (OOP) requirements.
−Removed: With the recent change in US Presidency, the status of Executive Actions and drug price lowering proposals from the prior Administration are unknown.
−Removed: For example, on May 11, 2018, the prior Administration issued a plan to lower drug prices.
−Removed: Under this blueprint for action, the prior Administration indicated that the Department of Health and Human Services (HHS) will:
−Removed: take steps to end the gaming of regulatory and patent processes by drug makers to unfairly protect monopolies;
−Removed: advance biosimilars and generics to boost price competition;
−Removed: evaluate the inclusion of prices in drug makers’ ads to enhance price competition;
−Removed: speed access to and lower the cost of new drugs by clarifying policies for sharing information between insurers and drug makers;
−Removed: avoid excessive pricing by relying more on value-based pricing by expanding outcome-based payments in Medicare and Medicaid;
−Removed: work to give Part D plan sponsors more negotiation power with drug makers;
−Removed: examine which Medicare Part B drugs could be negotiated for a lower price by Part D plans, and improving the design of the Part B Competitive Acquisition Program;
−Removed: update Medicare’s drug-pricing dashboard to increase transparency;
−Removed: prohibit Part D contracts that include “gag rules” that prevent pharmacists from informing patients when they could pay less out-of-pocket by not using insurance;
−Removed: and require that Part D plan members be provided with an annual statement of plan payments, out-of-pocket spending and drug price increases.
−Removed: In addition, on December 23, 2019, the prior Administration published a proposed rulemaking that, if finalized, would allow states or certain other non-federal government entities to submit importation program proposals to FDA for review and approval.
−Removed: Applicants would be required to demonstrate their importation plans pose no additional risk to public health and safety and will result in significant cost savings for consumers.
−Removed: At the same time, FDA issued draft guidance that would allow manufacturers to import their own FDA-approved drugs that are authorized for sale in other countries (multi-market approved products).
−Removed: The future status of these actions is uncertain but are not dismissed from our planning since reducing drug prices has bipartisan support.
−Removed: All Orders not in their final stages of implementation are expected to be put on hold until the new Administration organizes its plan.
−Removed: Most notable are the Most Favored Nation pricing for Medicare Part B Top 50 Drugs proposal (since it may set precedent for Part D drugs) and the New Safe Harbor Protections for Rebates and Pharmacy Benefit Manager Service Fees.
−Removed: The latter will have access strategy and gross-to-net implications on any products we commercialize.
−Removed: At the state level, individual states are increasingly aggressive in passing legislation and implementing regulations designed to control pharmaceutical and biological product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to
−Removed: encourage importation from other countries and bulk purchasing.
+Added: At the state level, individual states are increasingly aggressive in passing legislation and implementing regulations designed to control pharmaceutical and biological product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing.
In addition, regional health care authorities and individual hospitals are increasingly using bidding procedures to determine what pharmaceutical products and which suppliers will be included in their prescription drug and other health care programs.
2 unchanged sentences
The demand for our products is predicated on our clinical trial strategy of attempting to achieve superiority against the standard-of-care.
+Added: If there are not adequate reimbursement levels, our business and results of operations could be adversely affected.
+Added: Human Capital
+Added: In order to be a competitive, innovative and successful Company, we believe it is critical to attract, engage, motivate and retain a dedicated, talented and innovative team of employees.
+Added: As part of these efforts, we strive to foster a diverse, equitable and inclusive community, invest in continuous learning and development, offer a competitive compensation and benefits program and provide a safe and healthy workplace.
Our success starts and ends with having the best talent and, as a result, we are focused on attracting, developing, and engaging our employees.
−Removed: During 2020, Summit has notably strengthened the team by successfully attracting a number of leading senior employees into the Company.
−Removed: These new employees have successful track records, are acknowledged leaders in their field and a number have strong connections with prestigious medical institutions.
−Removed: Our ability to recruit this caliber of individuals provides a strong endorsement of the Company.
+Added: In 2021, Summit has notably strengthened the team by continuing to attract a number of leading world class employees into the Company.
+Added: These new recruits have successful track records and are acknowledged leaders in their field.
As of December 31, 2021, we had 105 full-time employees and 110 total employees.
−Removed: None of our employees are represented by labor unions or covered by collective bargaining agreements.
−Removed: We consider our relationship with our employees to be good.
−Removed: The 2020 fiscal year brought challenging demands on our employees and once again they have responded with dedication and enthusiasm.
−Removed: Summit sets visible and clear o bjectives and key results targets through a simple but robust process to help us focus, communicate, measure and achieve these.
−Removed: This enables the Company to link diverse operations, lending purpose and unity to the entire company.
−Removed: They provide the clarity of purpose to empower employees to make decisions on operational strategies and establishes a high-performance culture by instituting transparency, a focus on results and increased accountability.
−Removed: Specifically, we have human capital objectives including immediate and future resource planning, retention of our employees, effective deployment of our talent and the development of our employees with the Company.
−Removed: We are committed to embedding a culture of diversity and inclusion across our Company.
+Added: Of our total workforce, approximately 67% work in research and development, and 33% work in finance, legal, information technology, general management and other administrative functions.
+Added: Approximately 60% and 40% of our workforce is located in the U.S.
+Added: and the U.K., respectively.
+Added: In 2021, we once again made challenging demands of our employees and they have responded with dedication and enthusiasm.
+Added: In 2021, Summit launched an engagement survey, in which over 80% of employees responded.
+Added: The results of this survey reflected an overall positive response by employees, particularly highlighting both the enjoyment of their work and the team they work with.
+Added: Compensation and Benefits
+Added: We provide robust compensation and benefits programs to attract, motivate and retain our employees.
+Added: In addition to competitive compensation, we provide generous benefits including employer contributions to pension/401k plans, an employee stock purchase plan, insurance benefits, healthcare programs and paid vacation.
+Added: We are committed to ensuring that our total compensation packages are competitive while supporting our business plans and strategies.
+Added: Diversity, Equity and Inclusion
+Added: We are committed to embedding a culture of diversity, equity and inclusion across our Company.
+Added: We believe that diversity of gender, race, ethnicity, sexual orientation, culture, education, background and experience fuels innovation and enables our employees to succeed.
This includes ensuring opportunity for all and embraces the positive effect that our diverse workforce brings.
−Removed: We do not tolerate any form of discrimination and our human capital policies focus on ensuring that our employment processes are free from discrimination on any grounds.
−Removed: We provide robust compensation and benefits programs to help meet the needs of our employees.
−Removed: In addition to competitive compensation, we provide generous benefits including employer contributions to pension and 401(k) plans, insurance benefits, healthcare programs, stock option awards and vacation entitlement.
−Removed: We are committed to the health and safety of all of our people and during 2020, as a result of the COVID-19 pandemic, we implemented additional safety procedures to protect our employees, including protocols regarding social distancing, daily onsite health checks and working remotely.
−Removed: Our experienced teams adapted quickly to the changes and have managed our business successfully during this challenging time.
+Added: We do not tolerate any form of discrimination and our employment policies and practices focus on ensuring that all our employment processes are free from discrimination or harassment on any grounds.
+Added: Approximately 60% of our employees are female and 62% of our executive team is female.
+Added: Learning and Development
+Added: We are committed to investing in learning and development for our employees.
+Added: Our employees have access to online training courses which cover a wide range of technical and business topics to help them develop their professional skills and explore other areas as they plan for their career and personal growth.
+Added: Our performance management process includes timely performance feedback and career development discussions which are critical to each employee’s continued growth and development within the organization.
+Added: Workplace Health and Safety and Pandemic Response
+Added: We are committed to the health and safety of all of our employees.
+Added: We accomplish this through strict compliance with applicable laws and regulations regarding workplace safety.
+Added: We have continued to maintain our focus on the health and safety of our employees especially as the COVID-19 pandemic has evolved, including maintaining protocols for social distancing, daily onsite health checks and allowing our employees to work remotely as necessary based upon local government health recommendations.
+Added: Our experienced teams continue to adapt quickly to the changes and have managed our business successfully during this challenging time.
Our Corporate Information
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Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.