On February 9, 2023 GSK plc (LSE/NYSE: GSK) reported that the US Food and Drug Administration (FDA) Oncologic Drugs Advisory Committee (ODAC) voted 8 to 5 in support of the question posed to the committee regarding whether data from two proposed single-arm trials will be "sufficient to characterize the benefits and risks" of Jemperli (dostarlimab-gxly) in the curative-intent setting for patients with mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) locally advanced rectal cancer (Press release, GlaxoSmithKline, FEB 9, 2023, View Source [SID1234626993]).

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Hesham Abdullah, Senior Vice President, Global Head of Oncology Development, GSK, said: "The Committee’s positive vote in favour of our proposed clinical trial programme for dostarlimab reinforces our plans to generate data in support of a future US regulatory submission for the potential treatment of patients with dMMR/MSI-H locally advanced rectal cancer, a patient population with significant unmet medical needs and a standard of care that results in serious quality of life concerns. We thank the committee for the constructive dialogue and we look forward to continued interactions with FDA as we progress our development programme."

The current standard of care (SoC) for patients with dMMR/MSI-H locally advanced rectal cancer is neoadjuvant chemoradiotherapy (CRT) followed by surgery and adjuvant chemotherapy.[i] Neoadjuvant CRT provides local tumour control in most patients, but nearly one-third ultimately die from distant metastasis[ii]. Additionally, SoC is associated with long-term adverse effects, including bowel, urinary and sexual dysfunction, secondary malignancy and infertility i.

As part of its proposed clinical trial programme, GSK is initiating a global, open-label, phase II clinical trial to investigate the efficacy and safety of dostarlimab-gxly as monotherapy – as a replacement for chemotherapy, radiation and/or surgery – for treatment-naïve patients with dMMR/MSI-H locally advanced rectal cancer. The primary endpoint of GSK’s proposed trial is clinical complete response for 12 months (cCR12) as assessed by Independent Central Review. Key secondary endpoints will include cCR for 36 months and event-free survival for three years by investigator assessment. In addition, the trial aims to confirm results generated in a separate ongoing investigator-initiated trial by researchers at Memorial Sloan Kettering Cancer Center (MSK). Researchers at MSK shared these findings in a late-breaking presentation at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting with simultaneous publication in The New England Journal of Medicine.i GSK intends to use data from the Company’s proposed trial, alongside data from MSK’s ongoing trial of 30 patients, to support a supplemental Biologics License Application (sBLA) for accelerated regulatory approval in this indication.

In January 2023, the US FDA granted dostarlimab-gxly Fast Track designation for the treatment of dMMR/MSI-H locally advanced rectal cancer. Fast Track designation is designed to accelerate the development and expedite the review of potential new medicines to treat serious conditions with unmet medical needs. In addition, the application could be eligible for priority review if supported by clinical data at the time of the submission to the FDA.

About dMMR/MSI-H rectal cancer

Rectal cancer is a form of cancer that starts in the rectum, the final section of the large intestine, and is often categorised as part of a group of cancers called colorectal cancer. Colorectal cancer is the third most commonly diagnosed cancer in the world.[iii] In the US, it is estimated that approximately 20,220 individuals are diagnosed annually with rectal cancer[iv]. Approximately 5-10% of all rectal cancers are dMMR/MSI-H, meaning that they contain abnormalities that affect the proper repair of DNA when copied in a cell.[v] Mismatch repair-deficient status is a biomarker that has been shown to predict response to immune checkpoint blockade with PD-1 therapy.[vi] [vii] Tumours with this biomarker are most commonly found in endometrial, colorectal and other gastrointestinal cancers but may also be found in other solid tumours.[viii] [ix] [x]

About Jemperli (dostarlimab-gxly)

Jemperli is a programmed death receptor-1 (PD-1)-blocking antibody that binds to the PD-1 receptor and blocks its interaction with the PD-1 ligands PD-L1 and PD-L2.[xi] GSK’s ambition is for dostarlimab to become the backbone of the Company’s ongoing immuno-oncology-based research and development programme when used alone and in combination with standard of care and future novel cancer therapies, particularly in patients with currently limited treatment options. Dostarlimab is being investigated in registrational enabling trials as monotherapy and as part of combination regimens, including in women with recurrent or primary advanced endometrial cancer, women with Stage III or IV non-mucinous epithelial ovarian cancer, and patients with other advanced solid tumours or metastatic cancers. Dostarlimab has not been approved anywhere in the world as monotherapy for treatment-naïve patients with dMMR/MSI-H locally advanced rectal cancer. The US FDA has granted dostarlimab Fast Track designation for the treatment of dMMR/MSI-H locally advanced rectal cancer.

Dostarlimab was discovered by AnaptysBio, Inc. and licensed to TESARO, Inc., under a collaboration and exclusive license agreement signed in March 2014. The collaboration has resulted in three monospecific antibody therapies that have progressed into the clinic. These are: dostarlimab (GSK4057190), a PD-1 antagonist; cobolimab, (GSK4069889), a TIM-3 antagonist; and GSK4074386, a LAG-3 antagonist. GSK is responsible for the ongoing research, development, commercialisation, and manufacturing of each of these medicines under the agreement.

Important Information for Jemperli in the EU

Indication

Jemperli is indicated as monotherapy for the treatment of adult patients with mismatch repair deficient (dMMR)/microsatellite instability high (MSI H) recurrent or advanced endometrial cancer that has progressed on or following prior treatment with a platinum containing regimen.

Refer to the Jemperli Reference Information for a full list of adverse events and the complete important safety information in the EU.

On February 9, 2023, F-star Therapeutics, Inc., a Delaware corporation (the "Company"), invoX Pharma Limited, a private limited company organized under the laws of England and Wales ("Parent") and Fennec Acquisition Incorporated, a Delaware corporation and a wholly owned subsidiary of Parent ("Purchaser" and together with the Company and Parent, the "Parties"), entered into Amendment No. 6 ("Amendment No. 6") to the Agreement and Plan of Merger, dated as of June 22, 2022, and as amended, by and among the Parties and Sino Biopharmaceutical Limited, a company organized under the laws of the Cayman Islands, as "Guarantor" (the "Merger Agreement"). Capitalized terms used in this Current Report on Form 8-K without being defined herein shall have the same meanings ascribed to them in the Merger Agreement (Filing, 8-K, F-star, FEB 9, 2023, View Source [SID1234626992]).

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The purpose of Amendment No. 6 is to extend the End Date of the Merger Agreement in order to provide additional time for the Parties to complete negotiations with the Committee on Foreign Investment in the United States ("CFIUS") on the definitive terms of a mitigation agreement and to complete the ongoing tender offer (the "Offer") whose expiration date has been extended to February 22, 2023, unless further extended, as described below.

The Parties believe they are in the late stages of negotiating definitive terms of such mitigation agreement in order to permit the removal of CFIUS’s Interim Order. However, there can be no assurances that the Parties will reach agreement with CFIUS on a mitigation agreement.

Other than as expressly modified pursuant to Amendment No. 6, the Merger Agreement, which was previously filed as Exhibit 2.1 to the Current Report on Form 8-K filed with the Securities and Exchange Commission (the "SEC") by the Company on June 23, 2022, remains in full force and effect as originally executed on June 22, 2022, as amended. The foregoing description of Amendment No. 6 does not purport to be complete and is subject to, and qualified in its entirety by, the full text of Amendment No. 6 attached hereto as Exhibit 2.1 to this Current Report on Form 8-K, which is incorporated herein by reference.

On February 9, 2023 Erasca presented its key milestones presentation (Presentation, Erasca, FEB 9, 2023, View Source [SID1234626990]).

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On February 9, 2023 Decibel Therapeutics (Nasdaq: DBTX), a clinical-stage biotechnology company dedicated to discovering and developing transformative treatments to restore and improve hearing and balance, reported that it will present findings from its drug discovery and development programs at the 46th Annual MidWinter Meeting of the Association for Research in Otolaryngology (ARO), being held in Orlando, Florida February 11–15, 2023 (Press release, Decibel Therapeutics, FEB 9, 2023, View Source [SID1234626989]).

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The Company will present new data on its lead investigational gene therapy product candidate, DB-OTO, as well as new data across its gene therapy pipeline. Decibel will also present additional data from the interim analysis of the Phase 1b clinical trial of DB-020 in patients receiving cisplatin chemotherapy.

Podium Presentations

Podium 1 | Precise Targeting of GJB2 Cells Results in Safe and Efficacious Gene Therapy in a Rodent Model of Hearing Loss Due to GJB2 Deficiency
Presenter: Kathryn Ellis, Ph.D.
Session Title: Gene Therapy
Date & Time: Saturday, February 11, 2:00 – 4:00 p.m. ET

Podium 26 | Development of DB-020, a Locally Administered Product for Protection Against Cisplatin-Induced Ototoxicity
Presenter: John Lee
Session Title: Cisplatin Ototoxicity
Date & Time: Tuesday, February 14, 10:30 a.m. – 12:30 p.m. ET

Poster Presentations

SU83 | Development of a Platform for Parallel Functional Evaluation of Cell Type Specific Synthetic Promoters for Gene Therapy

SU84 | Dual Vector Gene Therapy Approaches for STRC-Related Hearing Loss

MO83 | Nonclinical Pharmacology, Biodistribution, and Safety Studies Supporting the Clinical Development of DB-OTO (AAV1-Myo15-hOTOFv5) for Hearing Loss Due to Genetic Otoferlin Protein Deficiency

TU83 | Development of a Utricle Culture System for Exploring Dual AAV-Mediated Expression Kinetics of Human Otoferlin

TU232 | Advancing Bioinformatically Informed Targets to Achieve In Vivo Vestibular Regeneration

On February 9, 2023 Artios Pharma Limited (Artios), a clinical-stage biotech company pioneering the development of novel small molecule therapeutics that target the DNA damage response ("DDR") process in order to treat patients with a broad range of cancers, reported the initiation of a randomized, Phase 2 expansion cohort in the ongoing Phase 1/2 trial evaluating its ataxia telangiectasia and Rad3-related ("ATR") Inhibitor, ART0380, in combination with gemcitabine for the treatment of platinum resistant ovarian cancer (Press release, Artios Pharma, FEB 9, 2023, View Source [SID1234626988]).

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The initiation of the Phase 2 trial follows the successful Phase 1 dose escalation demonstrating a favorable safety and tolerability profile, clinical activity, and preferred pharmacokinetics with ART0380 in advanced solid tumors. The recommended Phase 2 dose of ART0380 monotherapy has been defined for both intermittent and continuous daily dosing schedules together with the regimen of ART0380 in combination with gemcitabine. Clinically active RECIST confirmed responses occurred across doses and in tumors harboring DDR deficiencies as predicted through Artios’ DcoDeR platform.

Dr. Niall Martin, Chief Executive Officer at Artios, said: "This is the first of three proof of concept Phase 2 studies planned to evaluate our potentially best-in-class ATR inhibitor, ART0380, that has demonstrated a favorable safety and tolerability profile and clinical activity in the Phase 1 dose escalation. We are delighted to be collaborating with ovarian cancer experts at GEICO in Spain on this important study that will help bolster our understanding of the therapeutic potential of ART0380 and further inform our clinical development strategy. We look forward to initial Phase 2 data expected in the first half of 2025."

Antonio Gonzalez-Martin, MD, PhD, President and Founding member of the Spanish Ovarian Cancer Research Group (GEICO), Principal Investigator for the trial, said: "Ovarian cancer continues to be a difficult to treat cancer that ultimately leads to relapse. We are excited to collaborate with Artios to help bring an ATR targeted therapy with the potential to be highly effective in patients with platinum-resistant disease who are in much need of innovative treatment options. The favorable pharmacokinetic profile enabling combination with DNA damaging agents offers the potential of a new treatment option for patients with platinum resistant ovarian cancer. We at GEICO are looking forward to offering this novel treatment approach to our patients in the trial."

The ongoing global, open-label, multi-center, Phase 1/2 study is investigating the safety, tolerability, pharmacokinetic profile, and preliminary efficacy of ART0380 (GEICO-114-O trial) as a monotherapy or in combination with gemcitabine or irinotecan. The randomized, Phase 2 portion is designed to evaluate intermittent dosing of ART0380 in combination with gemcitabine in 21-day cycles in patients with high grade serous ovarian, primary peritoneal or fallopian tube carcinoma. The Phase 2 expansion in combination with gemcitabine is expected to enroll up to 60 patients and will be conducted at multiple oncology centers across the United States and Spain.

ART0380 is a potent, selective, oral inhibitor of ATR, a master regulator of DNA replication stress response. ART0380 is being developed as an oral anti-cancer agent for the treatment of cancers that harbor defects in DNA repair and in combination with agents including those that cause DNA damage. ART0380 was originally in-licensed by Artios from The University of Texas MD Anderson Cancer Center and ShangPharma Innovation in 2019. The molecule was jointly developed as part of a collaboration between ShangPharma and MD Anderson’s Therapeutics Discovery Division.