On September 15, 2021 NuCana plc (NASDAQ: NCNA) reported it has completed enrollment of the number of patients in the ongoing Phase III NuTide:121 study required to conduct the first interim analysis (Press release, Nucana BioPharmaceuticals, SEP 15, 2021, View Source [SID1234587744]). The study, which is comparing Acelarin combined with cisplatin to the global standard of care, gemcitabine plus cisplatin, as a first-line treatment for patients with advanced biliary tract cancer, has enrolled 418 patients with measurable disease. The first interim analysis will be conducted after the 418th patient has completed 28 weeks of follow-up, which is expected to occur in the first half of 2022. NuCana believes that a statistically significant improvement in the Objective Response Rate (ORR) at the first interim analysis, accompanied by positive trends in other endpoints, has the potential to allow for accelerated approval of a new drug application (NDA) for Acelarin in the United States. Recruitment in the NuTide:121 study, which is intended to enroll up to 828 patients, is ongoing and NuCana believes subsequent analyses could provide the confirmatory data to support full (regular) approval.

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"We are very pleased to achieve this important enrollment milestone which brings us closer to our goal of developing more effective and safer medicines for patients with cancer," said Hugh S. Griffith, NuCana’s Founder and Chief Executive Officer. "Biliary tract cancer is a devastating disease and there is a significant need for more effective medicines. We are especially grateful to all of the patients, their families, the investigators and other health care professionals involved in the NuTide:121 study."

Mr. Griffith continued: "The primary objective of the first interim analysis is to demonstrate at least a 14% improvement in the ORR in the Acelarin plus cisplatin arm compared to the gemcitabine plus cisplatin arm. In the ABC-08 study of Acelarin plus cisplatin as a first-line treatment for patients with biliary tract cancer, an ORR of 44% was achieved among the evaluable population. This compared favorably to the ORR of 26% achieved among evaluable patients treated with gemcitabine plus cisplatin in the ABC-02 study, which established this regimen as the global standard of care. We look forward to announcing the outcome of this first interim analysis in the first half of 2022."

About NuTide:121

NuTide:121 is a global, multi-center, 1:1 randomized Phase 3 study comparing Acelarin, a ProTide transformation of gemcitabine, in combination with cisplatin, to gemcitabine in combination with cisplatin in up to 828 patients with advanced biliary tract cancer who have not previously received treatment for advanced disease. The primary endpoints of NuTide:121 are Overall Survival (OS) and Objective Response Rate (ORR) and the FDA-approved protocol includes three interim analyses. Based on the statistical analysis plan, and subject to any further regulatory guidance, the Company believes that a statistically significant improvement in ORR at either of the first two interim analyses, accompanied by positive trends in other endpoints, has the potential to allow for an accelerated approval of a new drug application (NDA) for Acelarin in the United States. Under this scenario, the NuTide:121 study would continue and the Company believes it could use the data from subsequent analyses as the confirmatory data required to support full (regular) approval. There are currently no agents approved for the first-line treatment of patients with biliary tract cancer.

About Biliary Tract Cancer

Biliary tract cancer, including cholangiocarcinoma, gallbladder and ampullary carcinoma, are a group of cancers originating in the biliary tract. The biliary tract is comprised of the gallbladder and interconnecting ducts responsible for the transport of bile from the liver to the gallbladder and small intestine. Approximately 178,000 new cases of biliary tract cancer are diagnosed each year worldwide, with more than 18,000 of those diagnoses in the United States. There are currently no agents approved for the first-line treatment of patients with advanced biliary tract cancer; however, the worldwide standard of care in these patients is the combination of gemcitabine and cisplatin. Patients receiving this regimen have a median overall survival of 11.7 months.

On September 15, 2021 4D pharma plc (AIM: DDDD, NASDAQ: LBPS), a pharmaceutical company leading the development of Live Biotherapeutic products (LBPs), a novel class of drug derived from the microbiome, reported that new biomarker analyses from two ongoing clinical trials of its lead immuno-oncology single strain Live Biotherapeutic, MRx0518, in both neoadjuvant and refractory solid tumor settings, at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress, September 16-21, 2021 (Press release, 4d Pharma, SEP 15, 2021, View Source [SID1234587762]).

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"At the core of 4D pharma’s platform is the importance of understanding the impact of Live Biotherapeutics on human biology to rationally select and develop candidates, predict and measure response. These new biomarker data provide us with critical guidance on the biological and mechanistic impact of MRx0518 therapy in patients with various solid tumors," said Dr. Alex Stevenson, Chief Scientific Officer, 4D pharma. "These new findings indicate the potential to predict patients most likely to respond to MRx0518 therapy based on tumor biology."

"Furthermore, the monotherapy data demonstrates that a short course of MRx0518 treatment is able to positively modulate prognostic indicators of immunotherapy response," he added. "We look forward to utilizing and implementing these important new findings as we work to progress this novel oncology Live Biotherapeutic through development towards approval."

Highlights of the two ESMO (Free ESMO Whitepaper) 2021 poster presentations:

Baseline biomarkers associated with clinical benefit in patients with solid tumors refractory to immune checkpoint inhibitors (ICIs) treated with live biotherapeutic MRx0518 in combination with pembrolizumab

Presentation Number: 1024P

Tumor biomarkers were assessed in patients with evaluable baseline samples (N = 12) in the ongoing Phase I/II study of MRx0518 in combination with anti-PD-1 immune checkpoint inhibitor (ICI) Keytruda (pembrolizumab)
At baseline, patients who achieved complete response, partial response or stable disease for at least six months (collectively ‘responders’, N=4) from the combination of MRx0518 with Keytruda (pembrolizumab) had significantly greater densities of CD3+FOXP3+CD8- regulatory T cells (Tregs) and CD3+KI67+ proliferating T cells in tumors at baseline, compared to patients with progressive disease (PD, N=8), p=0.0381 and p=0.0048, respectively.
In addition, significantly lower densities of CD68+ macrophages at baseline were observed in the tumor microenvironment of responders compared to patients with progressive disease, p=0.0303.
These data indicate the potential for MRx0518 to overcome Treg-mediated acquired resistance to cancer treatment, and presents a biomarker potentially able to identify patients most likely to respond to immunotherapy based on MRx0518. Further tumor sample analysis is ongoing for additional patients recruited into the study.

Neoadjuvant MRx0518 treatment is associated with significant gene and metagene signature changes in solid tumours

Presentation Number: 543P

Gene expression profiling of paired tumor samples pre- and post-MRx0518 monotherapy across multiple solid tumor types (N=15) showed that treatment with MRx0518 for two to four weeks was associated with anti-tumor immune activity including antigen presentation, innate immune processes, and interferon response.
Analysis of paired tumor samples also identified significant increases in mast cells, Th1, CD8+ T cell, neutrophil, endothelial cell and inflammatory chemokine metagene signatures following MRx0518 monotherapy.
Effects were particularly pronounced in the cohort of breast cancer patients (N=7), with significant increases observed in total and activated dendritic cells, CD8+ T cells and cytotoxic cells in the tumor micro-environment.
Functional metagene analysis also identified positive changes in prognostic indicators and metagene signatures predictive of immunotherapy response in patients with breast cancer, including inflammatory chemokines, cytotoxicity, lymphoid scores, and the Tumor Inflammation Signature (TIS)1 – demonstrated to retrospectively predict clinical benefit of anti-PD-(L)1 ICI therapy efficacy in various cancer types.
The immune biomarker data from this study of MRx0518, as a monotherapy dosed over a short period of just two to four weeks, demonstrates the potent activity of this oral Live Biotherapeutic directly on the human immune system, and the positive implications for clinical outcomes. This study is being conducted in collaboration with Imperial College London.

Both ePosters will be available under the "Posters and Publications" section of the 4D pharma website at www.4dpharmaplc.com at 7:30 GMT on Thursday 16th September 2021.

1 Ayers M, et al. J Clin Invest. 2017;127:2930–40

About MRx0518

MRx0518 is single strain Live Biotherapeutic product in development for the treatment of cancer. It is delivered as an oral capsule and stimulates the body’s immune system, directing it to produce cytokines and immune cells that are known to attack tumours. It is currently being evaluated in three clinical trials in cancer patients. MRx0518-I-001 is a neoadjuvant monotherapy study in a variety of solid tumours and is being conducted at Imperial College (London, UK). MRx0518-I-002 is in combination with KEYTRUDA (pembrolizumab) in patients who have previously progressed on anti PD-1 therapies. The Coordinating Investigator of the study is at The University of Texas MD Anderson Cancer Center, Houston, USA, with multiple additional sites in the US. The study is being conducted in collaboration with MSD, the tradename of Merck & Co., Inc., Kenilworth, NJ, USA. MRx0518-I-003 is in combination with preoperative radiotherapy in resectable pancreatic cancer. A fourth clinical trial, in collaboration with Merck KGaA and Pfizer Inc., of BAVENCIO (avelumab) in combination with MRx0518 as a first-line maintenance therapy for patients with locally advanced or metastatic urothelial carcinoma that has not progressed with first-line platinum-containing chemotherapy, is expected to commence in Q4 2021.

On September 15, 2021 Photocure ASA (OSE: PHO), the Bladder Cancer Company, reported a clinical data presentation and highlights from the 2021 American Urological Association Annual Congress (AUA2021), which was held virtually September 10-13, 2021 (Press release, PhotoCure, SEP 15, 2021, View Source [SID1234587785]). During the program, new results from a study using Blue Light Cystoscopy (BLC) with Cysview in the surveillance setting were reported in a podium presentation, and separately, BLC with Cysview was discussed in an Expert Presentation on Surgical Techniques.

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The American Urological Association (AUA) meeting is one of largest international meetings in the urology calendar. This year’s event included an innovative, evidence-based, quality program for urologists and urologic health care professionals worldwide.

Podium Presentation

Title: UTILITY OF BLUE LIGHT FLEXIBLE CYSTOSCOPY FOR BLADDER CANCER SURVEILLANCE AFTER INTRAVESICAL THERAPY

Presenter: Sanam Ladi Seyedian, M.D., University of Southern California

Session and Date: PD-63: Bladder: Cancer Non-Invasive III: Sept. 13, 2021

Results were provided by two high-volume treatment facilities that perform Blue Light Flexible Cystoscopy (BLFC) and are participants in the Blue Light Cystoscopy with Cysview Registry. In this study, data was captured from 277 office based BLFC examinations in 136 patients who received intravesical BCG or chemotherapy, as part of standard of care treatment for non-muscle invasive bladder cancer (NMIBC).

From these examinations, a total of 52 office-based biopsies were taken, of which 23 (44%) were confirmed as malignant. BLFC identified all 23 malignancies, demonstrating 100% sensitivity for cancer detection in this cohort, whereas analysis by cytology identified only 3 of the 23 confirmed malignancies. Additionally, from the 277 total examinations, 23 (8%) were White Light Cystoscopy (WLC) normal and BLFC abnormal. Of these 23 discordant results, 16 had office-based biopsies and cancer was confirmed in 9 cases (56%), which would have been missed by WLC alone.

The study authors concluded that office-based BLFC helps improve early detection of recurrence in cases with normal WLC and can aid in surveillance of patients receiving intravesical therapy, enhance performance of office-based biopsy and increase early detection of BCG unresponsive disease.

"The results from this study show that use of Blue Light Cystoscopy with Cysview for patient surveillance improved the ability to detect recurrent disease in this high-risk, recently-treated patient cohort, which can significantly impact future treatment decisions," said Dr. Sia Daneshmand, one of the study authors. "Early detection of recurrent or residual cancer during initial treatment is essential for properly risk-stratifying all bladder cancer patients, and confirming response to treatment on follow-up and can have a major impact on subsequent treatment pathways and patient outcomes. As a result, Blue Light Cystoscopy can be an important tool throughout the continuum of care for patients diagnosed with bladder cancer."

Dr. Sia Daneshmand, M.D., is a Professor of Urology with Clinical Scholar designation and serves as director of clinical research as well as the urologic oncology (SUO) fellowship director at the University of Southern California (USC) in Los Angeles.

Abstract Link: View Source

Expert Presentation

Title: ADVANCES IN ENDOSCOPIC TREATMENT OF BLADDER TUMORS

Presenter: Yair Lotan, M.D., UT Southwestern Medical Center

Session and Date: Plenary Session: Surgical Techniques: Sept. 10, 2021

In this presentation, Dr. Lotan emphasized the importance of BLC with Cysview in accurately detecting NMIBC, stratifying bladder tumors, and helping to perform a complete TURBT in the operating room. He also provided an expert perspective on how biopsy and fulguration in the surveillance setting can positively impact patient outcomes using BLC with Cysview in the office-based setting.

Dr. Lotan is a Professor of the Department of Urology at UT Southwestern and Jane and John Justin Distinguished Chair in Urology, In Honor of Claus G. Roehrborn, M.D. He is Vice chair of Clinical Affairs and chief of urologic oncology.

"The study results presented at this year’s AUA meeting as well as the discussion on BLC in the Surgical Techniques presentation underscores how critically important it is for patients to receive the proper bladder cancer care whether they are having tumor resection in the hospital or follow-up procedures" said Geoffrey Coy, Vice President and General Manager of North American Operations at Photocure. "These new study results also highlight the range of opportunities made possible by Blue Light Cystoscopy for urologists, and the benefits to patients, especially when including flexible Blue Light Cystoscopy in the office setting as part of the continuum of care. We remain focused on expanding the availability of the procedure so that more physicians and patients have access to this important solution."

Note to editors: All trademarks mentioned in this release are protected by law and are registered trademarks of Photocure ASA

About Bladder Cancer

Bladder cancer ranks as the seventh most common cancer worldwide with 1 720 000 prevalent cases (5-year prevalence rate)1a, 573 000 new cases and more than 200 000 deaths annually in 2020.1b

Approx. 75% of all bladder cancer cases occur in men.1 It has a high recurrence rate with an average of 61% in year one and 78% over five years.2 Bladder cancer has the highest lifetime treatment costs per patient of all cancers.3

Bladder cancer is a costly, potentially progressive disease for which patients have to undergo multiple cystoscopies due to the high risk of recurrence. There is an urgent need to improve both the diagnosis and the management of bladder cancer for the benefit of patients and healthcare systems alike.

Bladder cancer is classified into two types, non-muscle invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC), depending on the depth of invasion in the bladder wall. NMIBC remains in the inner layer of cells lining the bladder. These cancers are the most common (75%) of all BC cases and include the subtypes Ta, carcinoma in situ (CIS) and T1 lesions. In MIBC the cancer has grown into deeper layers of the bladder wall. These cancers, including subtypes T2, T3, and T4, are more likely to spread and are harder to treat.4

1 Globocan. a) 5-year prevalence / b) incidence/mortality by population.
Available at: View Source, accessed [April 2021].
2 Babjuk M, et al. Eur Urol. 2019; 76(5): 639-657
3 Sievert KD et al. World J Urol 2009;27:295–300
4 Bladder Cancer. American Cancer Society. View Source

About Hexvix/Cysview (hexaminolevulinate HCl)

Hexvix/Cysview is a drug that preferentially accumulates in cancer cells in the bladder making them glow bright pink during Blue Light Cystoscopy (BLC). BLC with Hexvix/Cysview improves the detection of tumors and leads to more complete resection, fewer residual tumors and better management decisions.

Cysview is the tradename in the U.S. and Canada, Hexvix is the tradename in all other markets. Photocure is commercializing Cysview/Hexvix directly in the U.S. and Europe and has strategic partnerships for the commercialization of Hexvix/Cysview in China, Canada, Chile, Australia, and New Zealand. Please refer to View Source for further information on our commercial partners.

On September 15, 2021 G1 Therapeutics, Inc. (Nasdaq: GTHX), a commercial-stage oncology company, reported that it will hire and train a 15-person oncology sales force to supplement the Boehringer Ingelheim oncology commercial team (Press release, G1 Therapeutics, SEP 15, 2021, View Source [SID1234587808]). The expansion will allow G1 to target top tier accounts in order to accelerate sales activities and help maximize the adoption of COSELA (trilaciclib).

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The new G1 sales representatives will supplement the existing Boehringer Ingelheim oncology commercial team. G1 entered into a three-year co-promotion agreement with Boehringer Ingelheim to collaborate on the commercialization of COSELA for its first indication in ES-SCLC. (press release)

"This additional sales force will allow us to expand the reach into our top tier accounts, who treat up to 50 percent of patients diagnosed with small cell lung cancer," said Andrew Perry, G1’s Chief Commercial Officer. "COSELA is the only multilineage myeloprotection therapy developed to proactively reduce the risk of some of the dangerous side effects of chemotherapy in certain patients. We envision working closely with our partners at BI to maximize demand and adoption of this important medicine among these top accounts, as we seek to ensure the availability of COSELA to as many appropriate patients living with ES-SCLC as possible."

On September 9, 2021, the G1 Board of Directors adopted the G1 Therapeutics, Inc. 2021 Sales Force Inducement Equity Incentive Plan (the "Plan"). There are 500,000 shares of common stock reserved under the Plan to be used exclusively for grants of awards to sales force individuals and support staff that were not previously employees or directors of G1, as an inducement material to the individuals’ entry into employment with G1 within the meaning of Rule 5635(c)(4) of the Nasdaq Listing Rules. The Plan was approved by the Board of Directors without stockholder approval pursuant to Rule 5635(c)(4), and the terms and conditions of the Plan are substantially similar to G1’s stockholder-approved 2017 Equity Incentive Plan, as amended.

About COSELA (trilaciclib) for Injection

COSELA (trilaciclib) was approved by the U.S. Food and Drug Administration on February 12, 2021.

Indication
COSELA (trilaciclib) is indicated to decrease the incidence of chemotherapy-induced myelosuppression in adult patients when administered prior to a platinum/etoposide-containing regimen or topotecan-containing regimen for extensive-stage small cell lung cancer.

Important Safety Information
COSELA is contraindicated in patients with a history of serious hypersensitivity reactions to trilaciclib.

Warnings and precautions include injection-site reactions (including phlebitis and thrombophlebitis), acute drug hypersensitivity reactions, interstitial lung disease (pneumonitis), and embryo-fetal toxicity.

The most common adverse reactions (>10%) were fatigue, hypocalcemia, hypokalemia, hypophosphatemia, aspartate aminotransferase increased, headache, and pneumonia.

This information is not comprehensive. Please click here for full Prescribing Information. View Source

To report suspected adverse reactions, contact G1 Therapeutics at 1-800-790-G1TX or call FDA at 1-800-FDA-1088 or visit www.fda.gov/medwatch.

On September 15, 2021 The board of directors of Abbott (NYSE: ABT) reported a quarterly common dividend of 45 cents per share (Press release, Abbott, SEP 15, 2021, View Source [SID1234587729]).

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This marks the 391st consecutive quarterly dividend to be paid by Abbott since 1924. The cash dividend is payable Nov. 15, 2021, to shareholders of record at the close of business on Oct. 15, 2021.

Abbott has increased its dividend payout for 49 consecutive years and is a member of the S&P 500 Dividend Aristocrats Index, which tracks companies that have increased dividends annually for at least 25 consecutive years.