A Phase 3 Study to Evaluate Cefepime-taniborbactam Compared to Meropenem in Adults With Ventilator Associated Bacterial Pneumonia (VABP) or Ventilated Hospital Acquired Bacterial Pneumonia (vHABP)

This is a Phase 3, randomized, multicenter, double-blind, non-inferiority study to evaluate the efficacy and safety of cefepime-taniborbactam compared to meropenem in patients ≥ 18 years of age with ventilated HABP or VABP.

Start Date01 Oct 2024

Sponsor / Collaborator

Venatorx Pharmaceuticals, Inc.

[+1]

NCT04951505 / CompletedPhase 1

A Phase 1 Study to Evaluate the Safety and Intrapulmonary Pharmacokinetics of Cefepime and Taniborbactam in Healthy Subjects

This is a single-center, open-label study to assess the safety and intrapulmonary pharmacokinetics of cefepime and taniborbactam in healthy adult male and female subjects. Thirty subjects will receive a total of 6 doses of cefepime-taniborbactam (2 g cefepime/0.5g taniborbactam) administered intravenously every 8 hours. Following the sixth dose of cefepime-taniborbactam, subjects will be assigned to one of six bronchoscopy sampling times.

Start Date29 Jun 2021

Sponsor / Collaborator

Venatorx Pharmaceuticals, Inc.

CTR20191681 / CompletedPhase 1

头孢吡肟/VNRX-5133在中国健康受试者中单剂和多剂静脉输注给药的药代动力学、安全性和耐受性的1期临床试验

[Translation] Phase 1 clinical trial of the pharmacokinetics, safety, and tolerability of single and multiple intravenous infusions of cefepime/VNRX-5133 in healthy Chinese subjects

1. 评价中国健康受试者中头孢吡肟/VNRX-5133单剂和多剂静脉（IV）输注给药的药代动力学。 2. 评价中国健康受试者中头孢吡肟/VNRX-5133单剂和多剂静脉输注给药的安全性和耐受性。

[Translation]

1. To evaluate the pharmacokinetics of single and multiple intravenous (IV) infusions of cefepime/VNRX-5133 in healthy Chinese subjects. 2. To evaluate the safety and tolerability of single and multiple intravenous infusions of cefepime/VNRX-5133 in healthy Chinese subjects.

Start Date06 Jun 2020

Sponsor / Collaborator

Lyophilization Services of New England, Inc.

[+2]

100 Clinical Results associated with Cefepime Hydrochloride/Taniborbactam

100 Translational Medicine associated with Cefepime Hydrochloride/Taniborbactam

100 Patents (Medical) associated with Cefepime Hydrochloride/Taniborbactam

3,187

Literatures (Medical) associated with Cefepime Hydrochloride/Taniborbactam

01 Mar 2024·European journal of obstetrics, gynecology, and reproductive biology

Diagnosis and management of complications following pelvic organ prolapse surgery using a synthetic mesh: French national guidelines for clinical practice

Review

Author: Venara, Aurélien ; Vidart, Adrien ; Revel-Delhom, Christine ; Levesque, Amélie ; Rigaud, Jérome ; Perrouin-Verbe, Marie-Aimée ; Bosset, Pierre-Olivier ; Thubert, Thibault ; Deffieux, Xavier ; Lucot, Jean-Philippe ; Donon, Laurence ; Campagne-Loiseau, Sandrine ; Hermieu, Jean François ; Stivalet, Nadja

PREOPERATIVE PATIENTS' INFORMATION:

Each patient must be informed concerning the risks associated with POP surgery (EO).

HEMORRHAGE, HEMATOMA:

Vaginal infiltration using a vasoconstrictive solution is not recommended during POP surgery by the vaginal route (grade C). The placement of vaginal packing is not recommended following POP surgery by the vaginal route (grade C). During laparoscopic sacral colpopexy, when the promontory seems highly dangerous or when severe adhesions prevent access to the anterior vertebral ligament, alternative surgical techniques should be discussed per operatively, including colpopexy by lateral mesh laparoscopic suspension, uterosacral ligament suspension, open abdominal mesh surgery, or surgery by the vaginal route (EO).

BLADDER INJURY:

When a bladder injury is diagnosed, bladder repair by suturing is recommended, using a slow resorption suture thread, plus monitoring of the permeability of the ureters (before and after bladder repair) when the injury is located at the level of the trigone (EO). When a bladder injury is diagnosed, after bladder repair, a prosthetic mesh (polypropylene or polyester material) can be placed between the repaired bladder and the vagina, if the quality of the suturing is good. The recommended duration of bladder catheterization following bladder repair in this context of POP mesh surgery is from 5 to 10 days (EO).

URETER INJURY:

After ureteral repair, it is possible to continue sacral colpopexy and place the mesh if it is located away from the ureteral repair (EO).

RECTAL INJURY:

Regardless of the approach, when a rectal injury occurs, a posterior mesh should not be placed between the rectum and the vagina wall (EO). Concerning the anterior mesh, it is recommended to use a macroporous monofilament polypropylene mesh (EO). A polyester mesh is not recommended in this situation (EO).

VAGINAL WALL INJURY:

After vaginal wall repair, an anterior or a posterior microporous polypropylene mesh can be placed, if the quality of the repair is found to be satisfactory (EO). A polyester mesh should not be used after vaginal wall repair (EO).

MESH INFECTION (ABSCESS, CELLULITIS, SPONDYLODISCITIS):

Regardless of the surgical approach, intravenous antibiotic prophylaxis is recommended (aminopenicillin + beta-lactamase inhibitor: 30 min before skin incision +/- repeated after 2 h if surgery lasts longer) (EO). When spondylodiscitis is diagnosed following sacral colpopexy, treatment should be discussed by a multidisciplinary group, including especially spine specialists (rheumatologists, orthopedists, neurosurgeons) and infectious disease specialists (EO). When a pelvic abscess occurs following synthetic mesh sacral colpopexy, it is recommended to carry out complete mesh removal as soon as possible, combined with collection of intraoperative bacteriological samples, drainage of the collection and targeted antibiotic therapy (EO). Non-surgical conservative management with antibiotic therapy may be an option (EO) in certain conditions (absence of signs of sepsis, macroporous monofilament polypropylene type 1 mesh, prior microbiological documentation and multidisciplinary consultation for the choice of type and duration of antibiotic therapy), associated with close monitoring of the patient.

BOWEL OCCLUSION RELATED TO NON-CLOSURE OF THE PERITONEUM:

Peritoneal closure is recommended after placement of a synthetic mesh by the abdominal approach (EO).

URINARY RETENTION:

Preoperative urodynamics is recommended in women presenting with urinary symptoms (bladder outlet obstruction symptoms, overactive bladder syndrome or incontinence) (EO). It is recommended to remove the bladder catheter at the end of the procedure or within 48 h after POP surgery (grade B). Bladder emptying and post-void residual should be checked following POP surgery, before discharge (EO). When postoperative urine retention occurs after POP surgery, it is recommended to carry out indwelling catheterization and to prefer intermittent self-catheterization (EO).

POSTOPERATIVE PAIN:

Before POP surgery, the patient should be asked about risk factors for prolonged and chronic postoperative pain (pain sensitization, allodynia, chronic pelvic or non-pelvic pain) (EO). Concerning the prevention of postoperative pain, it is recommended to carry out a pre-, per- and postoperative multimodal pain treatment (grade B). The use of ketamine intraoperatively is recommended for the prevention of chronic postoperative pelvic pain, especially for patients with risk factors (preoperative painful sensitization, allodynia, chronic pelvic or non-pelvic pain) (EO). Postoperative prescription of opioids should be limited in quantity and duration (grade C). When acute neuropathic pain (sciatalgia or pudendal neuralgia) resistant to level I and II analgesics occurs following sacrospinous fixation, a reintervention is recommended for suspension suture removal (EO). When chronic postoperative pain occurs after POP surgery, it is recommended to systematically seek arguments in favor of neuropathic pain with the DN4 questionnaire (EO). When chronic postoperative pelvic pain occurs after POP surgery, central sensitization should be identified since it requires a consultation in a chronic pain department (EO). Concerning myofascial pain syndrome (clinical pain condition associated with increased muscle tension caused by myofascial trigger points), when chronic postoperative pain occurs after POP surgery, it is recommended to examine the levator ani, piriformis and obturator internus muscles, so as to identify trigger points on the pathway of the synthetic mesh (EO). Pelvic floor muscle training with muscle relaxation is recommended when myofascial pain syndrome is associated with chronic postoperative pain following POP surgery (EO). After failure of pelvic floor muscle training (3 months), it is recommended to discuss surgical removal of the synthetic mesh, during a multidisciplinary discussion group meeting (EO). Partial removal of synthetic mesh is indicated when a trigger point is located on the pathway of the mesh (EO). Total removal of synthetic mesh should be discussed during a multidisciplinary discussion group meeting when diffuse (no trigger point) chronic postoperative pain occurs following POP surgery, with or without central sensitization or neuropathic pain syndromes (EO).

POSTOPERATIVE DYSPAREUNIA:

When de novo postoperative dyspareunia occurs after POP surgery, surgical removal of the mesh should be discussed (EO).

VAGINAL MESH EXPOSURE:

To reduce the risk of vaginal mesh exposure, when hysterectomy is required during sacral colpopexy, subtotal hysterectomy is recommended (grade C). When asymptomatic vaginal macroporous monofilament polypropylene mesh exposure occurs, systematic imaging is not recommended. When vaginal polyester mesh exposure occurs, pelvic +/- lumbar MRI (EO) should be used to look for an abscess or spondylodiscitis, given the greater risk of infection associated with this type of material. When asymptomatic vaginal mesh exposure of less than 1 cm2 occurs in a woman with no sexual intercourse, the patient should be offered observation (no treatment) or local estrogen therapy (EO). However, if the patient wishes, partial excision of the mesh can be offered. When asymptomatic vaginal mesh exposure of more than 1 cm2 occurs or if the woman has sexual intercourse, or if it is a polyester prosthesis, partial mesh excision, either immediately or after local estrogen therapy, should be offered (EO). When symptomatic vaginal mesh exposure occurs, but without infectious complications, surgical removal of the exposed part of the mesh by the vaginal route is recommended (EO), and not systematic complete excision of the mesh. Following sacral colpopexy, complete removal of the mesh (by laparoscopy or laparotomy) is only required in the presence of an abscess or spondylodiscitis (EO). When vaginal mesh exposure recurs after a first reoperation, the patient should be treated by an experienced team specialized in this type of complication (EO).

SUTURE THREAD VAGINAL EXPOSURE:

For women presenting with vaginal exposure to non-absorbable suture thread following POP surgery with mesh reinforcement, the suture thread should be removed by the vaginal route (EO). Removal of the surrounding mesh is only recommended when vaginal mesh exposure or associated abscess is diagnosed.

BLADDER AND URETERAL MESH EXPOSURE:

When bladder mesh exposure occurs, removal of the exposed part of the mesh is recommended (grade B). Both alternatives (total or partial mesh removal) should be discussed with the patient and should be debated during a multidisciplinary discussion group meeting (EO).

01 Feb 2024·European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology

Multidrug-resistant Gram-negative clinical isolates with reduced susceptibility/resistance to cefiderocol: which are the best present and future therapeutic alternatives?

Article

Author: Freire, Samanta ; Le Terrier, Christophe ; Poirel, Laurent ; Nordmann, Patrice

Abstract:

Purpose:

To evaluate the different present and future therapeutic β-lactam/β-lactamase inhibitor (BL/BLI) alternatives, namely aztreonam-avibactam, imipenem-relebactam, meropenem-vaborbactam, cefepime-zidebactam, cefepime-taniborbactam, meropenem-nacubactam, and sulbactam-durlobactam against clinical isolates showing reduced susceptibility or resistance to cefiderocol in Enterobacterales, Acinetobacter baumannii, and Pseudomonas aeruginosa.

Methods:

MIC values of aztreonam, aztreonam-avibactam, cefepime, cefepime-taniborbactam, cefepime-zidebactam, imipenem, imipenem-relebactam, meropenem, meropenem-vaborbactam, meropenem-nacubactam, sulbactam-durlobactam, and cefiderocol combined with a BLI were determined for 67, 9, and 11 clinical Enterobacterales, P. aeruginosa or A. baumannii isolates, respectively, showing MIC values of cefiderocol being ≥1 mg/L. If unavailable, the respective β-lactam breakpoints according to EUCAST were used for BL/BLI combinations.

Results:

For Enterobacterales, the susceptibility rates for aztreonam, cefepime, imipenem, and meropenem were 7.5%, 0%, 10.4%, and 10.4%, respectively, while they were much higher for cefepime-zidebactam (91%), cefiderocol-zidebactam (91%), meropenem-nacubactam (71.6%), cefiderocol-nacubactam (74.6%), and cefiderocol-taniborbactam (76.1%), as expected. For P. aeruginosa isolates, the higher susceptibility rates were observed for imipenem-relebactam, cefiderocol-zidebactam, and meropenem-vaborbactam (56% for all combinations). For A. baumannii isolates, lower susceptibility rates were observed with commercially or under development BL/BLI combos; however, a high susceptibility rate (70%) was found for sulbactam-durlobactam and when cefiderocol was associated to some BLIs.

Conclusions:

Zidebactam- and nacubactam-containing combinations showed a significant in vitro activity against multidrug-resistant Enterobacterales clinical isolates with reduced susceptibility to cefiderocol. On the other hand, imipenem-relebactam and meropenem-vaborbactam showed the highest susceptibility rates against P. aeruginosa isolates. Finally, sulbactam-durlobactam and cefiderocol combined with a BLI were the only effective options against A. baumannii tested isolates.

01 Mar 2024·European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology

Molecular analysis of metallo-beta-lactamase-producing Pseudomonas aeruginosa in Switzerland 2022–2023

Article

Abstract:

Objectives:

The occurrence of metallo-beta-lactamase-producing Pseudomonas aeruginosa (MBL-PA) isolates is increasing globally, including in Switzerland. The aim of this study was to characterise, phenotypically and genotypically, the MBL-PA isolates submitted to the Swiss National Reference Center for Emerging Antibiotic Resistance (NARA) reference laboratory over a 12-month period from July 2022 to July 2023.

Methods:

Thirty-nine non-duplicate MBL-PA Isolates were submitted to NARA over the study period from across Switzerland. Susceptibility was determined by broth microdilution according to EUCAST methodology. Whole-genome sequencing was performed on 34 isolates. Sequence types (STs) and resistance genes were ascertained using the Centre for Genomic Epidemiology platform. MBL genes, blaNDM-1, blaIMP-1, and blaVIM-2, were cloned into vector pUCP24 and transformed into P. aeruginosa PA14.

Results:

The most prevalent MBL types identified in this study were VIM (21/39; 53.8%) followed by NDM (11/39; 28.2%), IMP (6/39; 15.4%), and a single isolate produced both VIM and NDM enzymes. WGS identified 13 different STs types among the 39 isolates. They all exhibited resistance to cephalosporins, carbapenems, and the beta-lactam-beta-lactamase inhibitor combinations, ceftolozane-tazobactam, ceftazidime-avibactam, imipenem-relebactam, and meropenem-vaborbactam, and 8 isolates were cefiderocol (FDC) resistant. Recombinant P. aeruginosa strains producing blaNDM-1, blaIMP-1, and blaVIM-2 exhibited FDC MICs of 16, 8, and 1 mg/L, respectively.

Conclusions:

This study showed that the MBL-PA in Switzerland could be attributed to the wide dissemination of high-risk clones that accounted for most isolates in this study. Although FDC resistance was only found in 8 isolates, MBL carriage was shown to be a major contributor to this phenotype.

News (Medical) associated with Cefepime Hydrochloride/Taniborbactam

23 May 2024

·www.outsourcing-pharma.com

What can pharma companies do to get promising antimicrobials to the frontlines of drug resistance?

According to the report, the race to create antibiotics and antifungals to conquer superbugs is falling perilously short, which the authors say is putting people across the world at risk. However, a shift in research and development (R&D), including investment in access and stewardship planning, can make a significant impact against antimicrobial resistance (AMR). As most large research-based pharmaceutical companies are no longer active in antimicrobial research and development (R&D), there are very few new treatments making it to market, leaving patients vulnerable to the rapid spread of AMR. Despite this reality, a handful of projects in late-stage clinical development could have a significant impact. Difficult-to-treat invasive, rare fungal mold infections The foundation is tracking five drugs which include gepotidacin, a small molecule commercialized by GSK with a leading phase 3 program in urinary tract infections and F2G’s olorofim, a first of the new orotomide class of antifungals in development for the treatment of difficult-to-treat invasive, rare fungal mold infections. Innoviva’s zoliflodacin is another treatment being tracked and is said to be one of the most promising new treatments for gonorrhoeae currently in phase 3 clinical trials. According to a report in Nature Scientific Reports, studies have found very little resistance to the drug currently circulating in strains, and in-vitro experiments demonstrated that it is difficult to induce resistance. Venatorx’s cefepime-taniborbactam is also under the foundation’s radar. The beta-lactam/beta-lactamase inhibitor (BL/BLI) combination antibiotic is being developed for the treatment of complicated urinary tract infections and hospital acquired bacterial pneumonia. googletag.cmd.push(function () { googletag.display('text-ad1'); }); Pfizer's recently approved aztreonam-avibactam (Emblaveo) is the first β-lactam/β-lactamase inhibitor antibiotic combination approved in the European Union for treating serious infections in adult patients caused by multidrug-resistant gram-negative bacteria, including metallo-β-lactamase-producing bacteria. Emblaveo was reviewed under European Medicines Agency accelerated assessment procedure, used when a pharmaceutical product is of major interest for public health and therapeutic innovation. People living on the frontlines of drug resistance Collectively, these projects could save at least 160,000 lives annually by providing much-needed medicines to treat drug-resistant gonorrhoea, urinary tract infections, intra-abdominal infections, respiratory infections, and invasive fungal infections. While these diseases affect a wide range of patients globally, women and children- especially those living in low-and middle-income countries (LMICs)- are disproportionately affected. Jayasree Iyer, CEO, at the Access to Medicine Foundation, said: “We have a small, but effective, arsenal in the race to combat drug-resistant infections. The difference between us winning or losing this race depends on how companies enable access to people living on the frontlines of drug resistance.” The foundation said that findings reveal that companies are employing diverse range of strategies within their access and stewardship plans but structured advance planning has not yet become standard. Encouragingly, it said, four of the five companies in scope, GSK, Pfizer, Innoviva, and Venatorx, are conducting or initiating clinical trials that directly target children, signalling progress in closing the gap between adult and paediatric access. Tackling the sheer scale and pace of drug resistance Commitments for registration were identified in five LMICs: China, India, Mexico, South Africa, and Thailand. However, for 108 of 113 LMICs in scope, where people also face high burdens of the diseases targeted by these projects, it is currently unclear whether any of them will be made available upon initial approval. The report identifies opportunities and recommendations for companies in focus and outlines actionable steps for global stakeholders in antimicrobial R&D to promote widespread adoption of advance access and stewardship planning. Marijn Verhoef, director of operations and research, at the Access to Medicine Foundation, said: “Tackling the sheer scale and pace of drug resistance is a complex global health issue that will require action from pharmaceutical companies across several areas. This includes providing appropriate access and implementing stewardship measures to safeguard the effectiveness of innovative antimicrobials. Failure to do this will limit efforts to tackle drug resistance.” The foundation added that as global health stakeholders prepare for 2024 UN General Assembly's High-level Meeting on AMR, this report comes at a crucial moment, emphasising the urgent gaps that need attention.

Phase 3Drug Approval

16 May 2024

·www.biospace.com

Venatorx Pharmaceuticals Announces Changes to Executive Leadership

MALVERN, Pa.--(BUSINESS WIRE)-- Venatorx Pharmaceuticals, a private, pre-commercial pharmaceutical company focused on improving health outcomes for patients with multidrug-resistant bacterial infections and hard-to-treat viral infections, announced today several changes to its executive leadership team. Manos Perros, PhD, has been appointed to the Board of Directors as Executive Chairman. Dr. Perros is a distinguished pharmaceutical and biotech executive with an impressive track record that includes more than 25 years in life sciences research and development. He was previously Chief Executive Officer and co-founder of Entasis Therapeutics, where he successfully positioned the company as a leader in the antimicrobial space, resulting in its acquisition by Innoviva in 2022. While at Entasis, Dr. Perros oversaw the development of Xacduro, which recently earned U.S. Food and Drug Administration approval as the first targeted treatment for Acinetobacter baumannii pneumonia. Prior to founding Entasis, Dr. Perros held the positions of Vice President and Head of AstraZeneca’s Infection Research and Early Development organization and Site Head for AstraZeneca’s Boston R&D research center. Dr. Perros also served as Director of the Novartis Institute for Tropical Diseases in Singapore, and Vice-President and Chief Scientific Officer, Antivirals, at Pfizer, where he led an R&D program that culminated in the approval of Selzentry, a first-in-class treatment for HIV. Dr. Perros’ appointment follows the resignation of Christopher J. Burns, Ph.D., who has stepped down as Chief Executive Officer and Director of Venatorx Pharmaceuticals. Additionally, Tomas J. Heyman has stepped down as Non-Executive Chairman of the Board. “On behalf of the entire Company, I would like to personally thank Chris for his dedication and tireless perseverance to lead Venatorx for over 14 years as an innovative pioneer in the fight against anti-microbial resistance. The Board of Directors sincerely appreciates his contributions along with the endless support and leadership that have guided the Company toward achieving its mission. I am delighted to join Venatorx Pharmaceuticals and to have an opportunity to help advance cefepime-taniborbactam through regulatory review and toward FDA approval to address the growing unmet need for novel treatments for patients suffering from multi-drug resistant gram-negative bacterial infections,” Dr. Perros said. “As recent Phase III data in The New England Journal of Medicine established, cefepime-taniborbactam met the primary noninferiority efficacy endpoint and demonstrated statistical superiority to meropenem for the treatment of complicated urinary tract infections (cUTIs), including acute pyelonephritis, while having a similar safety pro meropenem. This therapy has enormous potential and may represent a significant improvement over the standard of care that could support global health efforts to combat antibiotic-resistant infections for patients around the world.” About Venatorx Pharmaceuticals, Inc. Venatorx is a private, late-stage clinical pharmaceutical company focused on improving health outcomes for patients with multidrug-resistant bacterial infections and hard-to-treat viral infections. Venatorx’s lead program, cefepime-taniborbactam, is a clinical-stage antibiotic that successfully completed a Phase 3 study in adults with complicated urinary tract infections (cUTI), including pyelonephritis. In October 2022, BARDA awarded a contract of up to $318M for development and procurement of cefepime-taniborbactam for the treatment of melioidosis and multi-drug resistant infections. Venatorx is also developing an oral antibacterial, ceftibuten-ledaborbactam (formerly known as VNRX-7145), for the treatment of cUTI, including pyelonephritis, caused by certain bacteria in adult patients with limited treatment options; this product is completing Phase 1 and will advance directly to a global Phase 3 cUTI clinical trial. For more information about Venatorx and its anti-infectives portfolio, please visit . Forward Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation statements regarding the potential, safety, efficacy, and regulatory and clinical development of Venatorx Pharmaceuticals’ product candidates.

Phase 3Executive ChangeDrug ApprovalAcquisitionClinical Result

27 Mar 2024

·www.biospace.com

Everest Medicines Announces Financial Results for Full Year Ended December 31, 2023

SHANGHAI, March 27, 2024 /PRNewswire/ -- Everest Medicines (HKEX 1952.HK, "Everest", or the "Company"), a biopharmaceutical company focused on the discovery, clinical development, manufacturing and commercialization of innovative medicines and vaccines, today announced its financial results for the full year ended December 31, 2023, along with a corporate update. "2023 was an exciting year for Everest as we transformed into a fully integrated biopharmaceutical company with full value chain of capabilities," commented Rogers Yongqing Luo, CEO of Everest Medicines. "We have taken a lean and focused approach to commercialization, and built an effective commercial organization around the launch of our first product, Xerava®, in the Chinese market at the end of July. Nefecon®, the first-in-disease treatment for adults with primary IgAN and our blockbuster product in the renal portfolio, was also approved in mainland China and commercially launched in Macau in December 2023. The successful sales of these two products resulted in the ninefold increase in revenue last year to RMB125.9 million, significantly exceeding our guidance in mid-2023. Nefecon® will be launching in mainland China soon and our anchor product in the autoimmune space etrasimod is expected to receive approval in Macau and start commercialization in the Greater Bay area this year, so Everest will have three commercialized products before end of 2024. With these product launches and several other drugs advancing through clinical and regulatory approval stages, we have paved the way for even more substantial growth in 2024 and set a revenue guidance of RMB700 million. " "We also head into 2024 with an upgraded dual-engine approach to our pipeline growth strategy, which is in-house discovery plus in-licensing. As we terminated the collaboration and licensing agreements with Providence, we will develop our own discovery products utilizing this mRNA platform, but now hold full intellectual property rights and global rights. We have developed cancer vaccines from this platform which will enter clinical stage this year. Meanwhile, we will continue our in-licensing efforts, focused on our carefully chosen, less-crowded therapeutic areas of renal disease, infectious disease and autoimmune disease. This dual-engine approach will enable us to further capitalize on our commercial organization's capabilities to maximize synergies in our core product areas, while developing those products we have full intellectual property rights and global rights," Mr. Luo concluded. Recent Key Product Highlights and Anticipated Milestones RENAL PRODUCTS PORTFOLIO Nefecon® 2023 - In February 2023, South Korea's Ministry of Food and Drug Safety (MFDS) granted Global Innovative product on Fast Track (GIFT) designation to Nefecon® for the treatment of primary IgAN. - In March 2023, partner Calliditas reported positive topline results from the global, randomized, double-blind, placebo-controlled Phase 3 clinical trial NefIgArd, which investigated the effect of Nefecon® versus placebo in patients with primary IgAN over 2 years. The trial met its primary endpoint with Nefecon® demonstrating a highly statistically significant benefit over placebo (p value < 0.0001) in estimated glomerular filtration rate (eGFR) over the two-year period of 9-months of treatment with Nefecon® or placebo and 15-months of follow-up off drug. The key primary endpoint, eGFR over 2 years, was on average 5.05 mL/min/1.73 m2 higher with Nefecon® compared to placebo (p<0.0001). A treatment benefit on eGFR was apparent across baseline urine protein creatinine ratio (UPCR) subgroups, and sustained proteinuria effects and long lasting eGFR treatment benefit were observed even 15 months after discontinuation, supporting disease modification. The results also indicate that Nefecon® was generally well-tolerated. - In April 2023, the Company launched Nefecon® for clinical use in Shanghai Ruijin Hospital's Hainan Bo'ao subsidiary through an early-access program. The launch of this early-access program in Hainan marked the beginning of a new treatment era for IgA nephropathy in China. - In June 2023, our partner Calliditas presented data from the NeflgArd Phase 3 Study at the European Renal Association — European Dialysis and Transplant Association Congress (ERA-EDTA). The presentations showed data and analyses from the NefIgArd Phase 3 clinical trial evaluating Nefecon® in patients with IgAN. In addition to data disclosed in March, at 24 months, eGFR was reduced by 6.11 mL/min/1.73 m2 from baseline in the Nefecon® arm compared with 12.00 mL/min/1.73 m2 reduction in the placebo arm, demonstrating 50% less loss of kidney function. - In August 2023, the Company announced the completion of patient enrollment for the China open-label extension (cOLE) of the Phase 3 NefIgArd study. The cOLE study offers an additional 9 months of treatment with Nefecon® to all qualifying patients who have completed the NefIgArd study and evaluates the efficacy and safety of extended and repeated Nefecon® treatment in patients with IgAN. We hope this will provide more insight into Nefecon future clinical use. - In October 2023, our partner Calliditas presented new biomarker and subgroup analyses from Nefecon®'s Phase 3 NefIgArd study in both posters and oral presentations at the 17th International Symposium on IgA Nephropathy. Investigation of the effect of Nefecon® on circulating levels of IgA-IC in the Part A population of the NefIgArd clinical trial showed that patients treated with Nefecon® 16mg/day exhibited a statistically significant decrease in IgA-IC levels compared to patients who received placebo when evaluated at the 3-, 6- and 9-months post randomization. Suppression by treatment with Nefecon® of both IgA-IC formation and galactose-deficient IgA1 as previously reported offers an unprecedented opportunity to target the fundamental immune abnormalities that drive IgA deposition in the kidney and development of IgAN. - In October 2023, the Pharmaceutical Administration Bureau of the Macau Special Administrative Region, China, approved the New Drug Application (NDA) for Nefecon® for the treatment of IgAN in adults at risk of disease progression. - In November 2023, the Company made a late-breaking poster presentation at the American Society of Nephrology (ASN) Kidney Week 2023 on Chinese patients enrolled from mainland China. Clinical results from the global Phase 3 trials of Nefecon® demonstrated even stronger results in the subpopulation of patients from mainland China. At 24 months, the eGFR in the Chinese patients was 66% less deteriorated compared to 50% in the global population. The mean percent reduction in UPCR was 31% greater at 9 months vs. placebo in Chinese patients and 43% greater than placebo at 24 months. Lastly, the percent of Chinese patients without microhematuria during the observational follow-up period increased to 57.5% from 26.9% at baseline, while it was maintained at 14.3% in the placebo group. These data demonstrate Chinese patients show faster disease progression compared to the global population. - In November 2023, China's National Medical Products Administration (NMPA) approved Nefecon® for the treatment of primary IgAN in adults at risk of disease progression. China has the highest prevalence of primary glomerular diseases in the world with an estimated five million IgAN patients. - In November 2023, the Nefecon® NDA was accepted for review by South Korea's Ministry of Food and Drug Safety (MFDS) for the treatment of primary IgAN in adult patients. - In December 2023, partner Calliditas announced that the U.S. Food and Drug Administration (FDA) had fully approved Nefecon® delayed release capsules to reduce the loss of kidney function in adults with IgAN at risk for disease progression, irrespective of proteinuria levels. - In December 2023, Nefecon® issued its first prescription at Kiang Wu Hospital in Macau, marking the official start of the company's first-in-disease drug to patients across Asia, opening a new era of treatment for IgA nephropathy patients in the region. At the same time, a PAP program was officially launched at the Kiang Wu Hospital, which will provide financial assistance to Chinese mainland citizens who prescribe Nefecon® in Macau. - In December 2023 the New Drug Application (NDA) for Nefecon® was accepted for review by the Taiwan Food and Drug Administration (TFDA) for the treatment of primary IgAN in adult patients. 2024 - In March 2024, Singapore Health Sciences Authority (HSA) approved NEFEGAN® for the treatment of primary IgAN in adults at risk of disease progression. The NDA for NEFEGAN®, known in other Everest's territories as Nefecon®, was accepted by HSA in April 2023. - We expect Nefecon® to be commercially launched in mainland China, Hong Kong and Singapore in 2024 - We anticipate receiving Nefecon® NDA approvals in Taiwan and South Korea in 2024. - We expect to report Nefecon® China open label study results in 3Q 2024. INFECTIOUS DISEASE PORTFOLIO XERAVA® (eravacycline) 2023 - In March 2023, the NMPA of China approved the NDA for XERAVA® (eravacycline) for the treatment of complicated intra-abdominal infections (cIAI) in adult patients. The Company launched XERAVA® in July 2023 in mainland China. - In April 2023, the Company signed a Memorandum of Understanding for a strategic partnership with a subsidiary of Shanghai Pharma, SPH Keyuan Xinhua Pharmaceutical Co., Ltd. to promote import and channel distribution of XERAVA® (eravacycline) in China. - In July 2023, the Company launched XERAVA® (eravacycline) in China with its first prescription issued at Huashan Hospital affiliated to Fudan University. The commercialization of XERAVA® in China marks Everest's transformation into a commercial- stage innovative biopharmaceutical company. - In September 2023, the TFDA approved the NDA for XERAVA® (eravacycline) for the treatment of complicated intra-abdominal infections (cIAI) in adult patients in Taiwan. - In 2024, eravacycline's clinical breakpoint was officially approved by ECAST, so that the drug can be used more accurately in clinical practice. Cefepime-taniborbactam 2023 - In September 2023, the Center for Drug Evaluation of the China NMPA recommended Priority Review for cefepime-taniborbactam for the treatment of complicated urinary tract infections (cUTI), including pyelonephritis, based on the criteria of "innovative drugs for the prevention and treatment of major infectious diseases and rare diseases that meet urgent clinical needs." 2024 - In February 2024, partner Venatorx Pharmaceuticals announced that The New England Journal of Medicine (NEJM) published the results of the CERTAIN-1 Phase 3 clinical study of the investigational agent cefepime-taniborbactam for the treatment of adult patients with complicated urinary tract infections (cUTI), including acute pyelonephritis. The results showed that cefepime-taniborbactam was superior to meropenem for the treatment of complicated UTI that included acute pyelonephritis, with a similar safety pro meropenem. - We expect to submit NDA of the cUTI indication in China in 2024. AUTOIMMUNE DISEASE PORTFOLIO Etrasimod (VELSIPITY™) 2023 - In October 2023, licensing partner Pfizer Inc. received FDA approval for VELSIPITY™ (etrasimod) for adults with moderately to severely active ulcerative colitis (UC). - In November 2023, the Company reported positive topline data results from a multi-center Phase 3 clinical trial of etrasimod in Asia for the treatment of moderate-to-severe active ulcerative colitis (UC). Etrasimod treatment resulted in a clinically meaningful and statistically significant improvement in the primary endpoint and all key secondary and other secondary endpoints (including mucosal healing, symptomatic remission and endoscopic normalization) after the 12-week induction treatment period. The safety pro consistent with previous etrasimod studies and no new safety findings were observed. 2024 - In March 2024, Pharmaceutical Administration Bureau of the Macau Special Administrative Region, China, accepted Everest's NDA for etrasimod for the treatment of moderately to severely active ulcerative colitis. Macau is expected to be the first of Everest's Asian territories to get etrasimod regulatory approval. - We expect to report etrasimod topline results from the Phase 3 Asian clinical trial maintenance period in 2H 2024. - We expect to submit NDA for etrasimod to the China NMPA in 2H 2024. Zetomipzomib 2023 - In September 2023, Everest entered into a collaboration and license agreement with Kezar Life Sciences to develop and commercialize Kezar's lead drug candidate zetomipzomib, a novel, first-in-class, selective inhibitor of the immunoproteasome for a range of autoimmune diseases including lupus nephritis, in Greater China, South Korea and some Southeast Asian countries. 2024 - In February 2024, China's NMPA approved Kezar's IND application for initiation of the Phase 2b PALIZADE trial in China of zetomipzomib in patients with lupus nephritis (LN). Everest plans to join its partner, Kezar Life Sciences, in PALIZADE, a global, placebo-controlled Phase 2b clinical trial evaluating the efficacy and safety of two dose-levels of zetomipzomib in patients with active lupus nephritis. Commercialization We achieved RMB125.9 million in revenue in 2023, substantially above the previous guidance of RMB70-100 million. In 2023, the Company launched two products, developed a focused commercialization model driven by product clinical value, and built a 200-member lean and efficient commercial platform. This team worked on a concentrated strategy and managed to promote Xerava® in around 300 core tertiary hospitals in just five months, laying a solid foundation for our future commercial success. Xerava® has been recommended by multiple treatment guidelines in China and globally for multidrug-resistant bacterial infections. Nefecon® received NDA approvals in Macau and mainland China in Oct. 2023 and Nov. 2023, respectively and Everest plans to make the product available to an estimated five million patients in mainland China in 2024. The Company prepared for this launch by initiating an early access program in the Hainan Boao pilot zone. This program demonstrated significant demand for Nefecon®, with approximately 700 patients signed up. In addition, approximately 20,000 Chinese patients have registered in an IgAN patient program funded through a charity foundation, which underscores the significant unmet needs for this first-in-disease medicine and these patients will be a part of our patient base when Nefecon® is officially launched in mainland China. By the end of 2024, we expect to have three commercialized products in our core therapeutic areas. We will focus on successfully commercializing Nefecon® in China, continuing to grow the sales of Xerava®, while starting to commercialize etrasimod in the Greater Bay area. We expect to achieve a revenue target of RMB700 million in 2024 from the combined sales of Xerava® and Nefecon®. With our strong balance sheet and expected substantial increases in revenue, the Company has set a goal of reaching cash breakeven by the end of 2025. We will continue to increase patient access through patients registered for our charity program for Nefecon®, and gradually establish a second sales team of up to 120 nephrology-focused representatives commercializing Nefecon® across 600 hospitals, which covers approximately 60% of the IgAN patient population in China. We also plan to engage in National Reimbursement Drug List (NRDL) negotiations in 2024 for Nefecon®, with the goal to be included in 2025 so more patients can enjoy the benefits of the medicine. We plan to expand Nefecon approvals to additional territories, including Hong Kong, Taiwan and South Korea this year. Discovery Everest will develop its own products utilizing the mRNA platform, of which it now has full intellectual property rights and full global rights. Based on this clinically-validated mRNA platform, therapeutic vaccines such as cancer vaccines will be the focus of research and discovery activities at Everest. Everest plans to announce new mRNA pipeline products that are entering clinical stage in 2024. Business Development Our business development efforts centered around renal diseases and autoimmune disorders in 2023. We continue to bolster our leadership position in these areas by expanding our pipeline. In September 2023, the Company entered into a collaboration and license agreement with Kezar Life Sciences to develop and commercialize zetomipzomib in lupis nephritis and other potential autoimmune diseases. The in-licensing of zetomipzomib added another mid-to-late stage autoimmune asset to our pipeline. Going forward, we will continue to pursue first-in-class or best-in-class assets in our focused therapeutic areas, including commercial-stage products that could utilize our established commercial capabilities and complement our pipeline. In February 2024, Everest terminated the collaboration and license agreements with Providence Therapeutics Holdings Inc. Everest will continue to develop its own products utilizing the mRNA platform, and will own full intellectual property rights and full global rights of those products going forward, with no obligation to pay milestone or royalty fees for products it develops in the future, except for if we develop the rabies or shingles vaccines which were developed in collaboration with Providence. KEY CORPORATE DEVELOPMENTS In March 2023, the Company received full upfront payment of $280 million from Immunomedics, Inc., a wholly-owned subsidiary of Gilead Sciences, Inc., for Trodelvy® rights in certain Asian territories. We will work with partners to establish an innovative ecosystem for kidney disease diagnostics and treatment, with the aim to provide IgAN patients with a tool to diagnose the disease and show disease progression without biopsy. Financial Highlights IFRS Numbers: Revenue increased by RMB113.1 million or 884% to RMB125.9 million for the year ended 31 December 2023, from sales growth of Xerava® in Singapore, the launch of Xerava® in mainland China and Hong Kong, the launch of Nefecon® in Macau and sales of Trodelvy® during the transition period with Gilead in Singapore. Our general and administrative expenses decreased by RMB111.3 million or 40.3% to RMB165.2 million for the year ended 31 December 2023. The decrease was primarily attributable to optimization and rationalization of the organizational structure. Research and development (the "R&D") expenses decreased by RMB269.6 million or 33.3% to RMB540.1 million. The decrease was primarily attributable to a number of our drug candidates having completed clinical trials and advanced to the registration phase or commercial stages. Our distribution and selling expenses decreased by RMB95.3 million or 29.2% to RMB231.4 million for the year ended 31 December 2023. The decrease was primarily attributable to the building of a more efficient and leaner commercial team for optimal value creation. Net loss for the year increased by RMB597.2 million to RMB844.5 million for the year ended 31 December 2023, primarily attributable to gain from Trodelvy® transaction in 2022, which was a one-time item. Adjusted for one-time gain from Trodelvy transaction, net loss for the year declined by RMB725.1 million due to growth of product sales and optimization of the organizational structure. Cash and cash equivalents and term deposits amounted to RMB2,349.7 million as of 31 December 2023. Non-IFRS Measure: Adjusted loss for the year was RMB713.6 million for the year ended 31 December 2023, representing an increase of RMB696.2 million, primarily due to increased IFRS loss. Adjusted for one-time gain from Trodelvy transaction in 2022, loss for the year declined by RMB626.2million due to growth of product sales and optimization of the organizational structure. — Financial Table — Conference Call Information The English session of the conference call will be held at 9:00 AM on March 28, 2024 Beijing Time (9:00 PM U.S. Eastern Time on March 27, 2024) and the Mandarin session of the conference call will be held at 11:00 AM Beijing Time on the same day (11:00 PM U.S. Eastern Time on March 27, 2024). The conference calls can be accessed by the following links: For English Session: Time: 9:00 AM Beijing Time, Thursday, March 28, 2024 Pre-Registration Link: Webcast Link: Alternatively, participants may dial in to the conference call using below dial-in information: For Mandarin Session: Time: 11:00 AM Beijing Time, Thursday, March 28, 2024 Webcast Link: Alternatively, participants may dial into the conference call using below dial-in information: The replay of English session will be available shortly after the call and can be accessed by visiting the Company's website at . About Everest Medicines Everest Medicines is a biopharmaceutical company focused on discovering, developing, manufacturing and commercializing transformative pharmaceutical products and vaccines that address critical unmet medical needs for patients in Asian markets. The management team of Everest Medicines has deep expertise and an extensive track record from both leading global pharmaceutical companies and local Chinese pharmaceutical companies in high-quality discovery, clinical development, regulatory affairs, CMC, business development and operations. Everest Medicines has built a portfolio of first-in-disease or best-in-class products in the Company's therapeutic areas of interest including renal diseases, infectious diseases, autoimmune disorders and mRNA platform. For more information, please visit its website at . Forward-Looking Statements: This news release may make statements that constitute forward-looking statements, including descriptions regarding the intent, belief or current expectations of the Company or its officers with respect to the business operations and financial condition of the Company, which can be identified by terminology such as "will," "expects," "anticipates," "future," "intends," "plans," "believes," "estimates," "confident" and similar statements. Such forward-looking statements are not guarantees of future performance and involve risks and uncertainties, or other factors, some of which are beyond the control of the Company and are unforeseeable. Therefore, the actual results may differ from those in the forward-looking statements as a result of various factors and assumptions, such as future changes and developments in our business, competitive environment, political, economic, legal and social conditions. The Company or any of its affiliates, directors, officers, advisors or representatives has no obligation and does not undertake to revise forward-looking statements to reflect new information, future events or circumstances after the date of this news release, except as required by law. Company Codes: HongKong:1952

Phase 3Clinical ResultPhase 2License out/inDrug Approval

100 Deals associated with Cefepime Hydrochloride/Taniborbactam

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Indication	Highest Phase	Country/Location	Organization	Date
Complicated urinary tract infection	NDA/BLA	US	Venatorx Pharmaceuticals, Inc.	15 Aug 2023
Pyelonephritis	NDA/BLA	US	Venatorx Pharmaceuticals, Inc.	15 Aug 2023
Hospital-acquired pneumonia	Phase 3	-	Venatorx Pharmaceuticals, Inc.	01 Oct 2024
Pneumonia, Ventilator-Associated	Phase 3	-	Venatorx Pharmaceuticals, Inc.	01 Oct 2024
VABP	Phase 3	-	Venatorx Pharmaceuticals, Inc.	01 Oct 2024
Acute pyelonephritis	Phase 3	US	Everid Medicines (Beijing) Limited	07 Aug 2019
Acute pyelonephritis	Phase 3	US	Venatorx Pharmaceuticals, Inc.	07 Aug 2019
Acute pyelonephritis	Phase 3	AR	Venatorx Pharmaceuticals, Inc.	07 Aug 2019
Acute pyelonephritis	Phase 3	AR	Everid Medicines (Beijing) Limited	07 Aug 2019
Acute pyelonephritis	Phase 3	BR	Venatorx Pharmaceuticals, Inc.	07 Aug 2019

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03840148 (CERTAIN-1, Corporate Publications) Manual	Phase 3	Complicated urinary tract infection	661	Cefepime/Taniborbactam	qjizmqjali(ofbptuppxg) = sspklbowfd hrempsxrre (hcccswbktl ) View more	Superior	10 Mar 2022
				meropenem	qjizmqjali(ofbptuppxg) = izshgclpmm hrempsxrre (hcccswbktl ) View more

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