On December 2, 2022 GSK plc (LSE/NYSE: GSK) reported that the European Medicines Agency (EMA) validated the marketing authorisation application (MAA) for momelotinib, a potential new oral treatment for myelofibrosis (Press release, GlaxoSmithKline, DEC 2, 2022, View Source [SID1234624726]). Momelotinib has a differentiated mechanism of action, with inhibitory ability along three key signalling pathways: Janus kinase (JAK) 1, and JAK2 and activin A receptor type I (ACVR1), which could address the significant medical needs of myelofibrosis patients with anaemia.

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The MAA is based on results from key phase III trials, including the pivotal MOMENTUM trial, which met all primary and key secondary endpoints, including Total Symptom Score (TSS), Transfusion Independence (TI) rate and Splenic Response Rate (SRR). The primary analysis data from the MOMENTUM phase III trial were presented at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting and the European Hematology Association (EHA) (Free EHA Whitepaper) 2022 Hybrid Congress. Updated 48-week data will be presented at the upcoming American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition on 10-13 December 2022.

A Committee for Medicinal Products for Human Use (CHMP) regulatory action is anticipated by year-end 2023, and a New Drug Application for momelotinib is currently under regulatory review with the US Food and Drug Administration (FDA) with a Prescription Drug User Fee Act action date of 16 June 2023. Momelotinib is not currently approved in any market, but if approved by regulators, momelotinib would be the only medicine that addresses key manifestations of myelofibrosis, including anaemia, symptoms, and splenomegaly.

About the pivotal MOMENTUM phase III clinical trial

MOMENTUM is a global, randomised, double-blind phase III clinical trial of momelotinib versus danazol in patients with myelofibrosis who were symptomatic and anaemic and had been previously treated with a US FDA-approved JAK inhibitor. The trial was designed to evaluate the safety and efficacy of momelotinib for treating and reducing key hallmarks of the disease: symptoms, blood transfusions (due to anaemia) and splenomegaly (enlarged spleen).

The trial’s primary efficacy endpoint was TSS reduction of ≥50% over the 28 days immediately before the end of Week 24 compared to baseline TSS, using the Myelofibrosis Symptom Assessment Form. Key secondary endpoints included TI rate for ≥12 weeks immediately before the end of Week 24 with haemoglobin levels ≥ 8 g/dL and SRR based on splenic volume reduction of ≥35% at Week 24 from baseline.

Patients were randomised at 2:1 to receive either momelotinib or danazol (n=130 and n=65, respectively). After 24 weeks of treatment, patients on danazol were allowed to crossover to receive momelotinib. Early crossover to momelotinib was available for confirmed splenic progression. The trial enrolled 195 patients across 21 countries.

About momelotinib

Momelotinib is a potential new medicine with a differentiated mechanism of action, with inhibitory ability along three key signalling pathways: Janus kinase (JAK) 1 and JAK2 and activin A receptor type I (ACVR1).i,ii,iii,iv Inhibition of JAK1 and JAK2 may improve constitutional symptoms and splenomegaly.i,iii,iv Additionally, direct inhibition of ACVR1 leads to a decrease in circulating hepcidin, which is elevated in myelofibrosis and contributes to anaemia.i,ii,iii,iv

About myelofibrosis

Myelofibrosis is a rare blood cancer that results from dysregulated JAK-signal transducer and activator of transcription protein signalling and is characterised by constitutional symptoms, splenomegaly, and progressive anaemia. Myelofibrosis affects approximately 20,000 patients in the US, with about 40% of patients already anaemic at the time of diagnosis and nearly all patients estimated to develop anaemia eventually.i,v Patients will often require transfusions, and more than 30% will discontinue treatment due to anaemia.vi Anaemia and transfusion dependence strongly correlate with poor prognosis and shortened survival.

On December 2, 2022 GSK plc (LSE/NYSE: GSK) reported positive headline results from the planned interim analysis of Part 1 of the RUBY/ENGOT-EN6/GOG3031/NSGO phase III trial investigating Jemperli (dostarlimab) plus standard-of-care chemotherapy (carboplatin-paclitaxel) followed by Jemperli compared to chemotherapy plus placebo followed by placebo in adult patients with primary advanced or recurrent endometrial cancer (Press release, GlaxoSmithKline, DEC 2, 2022, View Source [SID1234624725]). The trial met its primary endpoint of investigator-assessed progression-free survival (PFS). It showed a statistically significant and clinically meaningful benefit in the prespecified mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) patient subgroup and in the overall population. A clinically relevant benefit in PFS was also observed in the mismatch repair proficient (MMRp)/microsatellite stable (MSS) patient subgroup.

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While the overall survival (OS) data were immature at the time of this analysis, a favourable trend was observed in the overall population, including both the dMMR/MSI-H and MMRp/MSS subgroups.

The safety and tolerability profile of dostarlimab in the RUBY phase III trial was consistent with clinical trials of similar regimens. The most common treatment-emergent adverse events in patients receiving dostarlimab plus chemotherapy were nausea, alopecia, fatigue, peripheral neuropathy, anaemia, arthralgia, constipation and diarrhoea.

Hesham Abdullah, Senior Vice President, Global Head of Oncology Development, GSK said: "Patients with primary advanced or recurrent endometrial cancer have limited treatment options. Long-term outcomes remain poor, and new treatment options are urgently needed to evolve the current standard of care, which is platinum-based chemotherapy. Based on these positive headline results from the RUBY phase III trial, GSK intends to seek regulatory approvals for a potential new indication for dostarlimab in the treatment of primary advanced or recurrent endometrial cancer."

Regulatory submissions based on the trial results are anticipated in the first half of 2023. Full results from the trial will be published in a medical journal and presented at an upcoming scientific meeting.

RUBY is part of an international collaboration between the European Network of Gynaecological Oncological Trial groups (ENGOT), a research network of the European Society of Gynaecological Oncology (ESGO) that consists of 22 trial groups from 31 European countries that perform cooperative clinical trials, and the GOG Foundation, a non-profit organisation dedicated to transforming the standard of care in gynaecologic oncology.

About endometrial cancer

Endometrial cancer is found in the inner lining of the uterus, known as the endometrium. It is the most common gynaecologic cancer in the US and the second most common gynaecologic cancer globally.1 Approximately 15-20% of women with endometrial cancer will be diagnosed with advanced disease at the time of diagnosis.2

About RUBY

RUBY is a two-part global, randomised, double-blind, multicentre phase III trial of patients with primary advanced or recurrent endometrial cancer. Part 1 is evaluating dostarlimab plus carboplatin-paclitaxel followed by dostarlimab versus carboplatin-paclitaxel plus placebo followed by placebo. Part 2 is evaluating dostarlimab plus carboplatin-paclitaxel followed by dostarlimab plus niraparib versus placebo plus carboplatin-paclitaxel followed by placebo. The primary endpoints in Part 1 are investigator-assessed PFS based on the Response Evaluation Criteria in Solid Tumours v1.1 and OS. In Part 2, the primary endpoint is investigator-assessed PFS. Secondary endpoints in Part 1 and Part 2 include PFS per blinded independent central review, overall response rate, duration of response, disease control rate, patient-reported outcomes, and safety and tolerability.

About Jemperli (dostarlimab)

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-L2.3 Dostarlimab is being investigated in registrational enabling studies, 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.

In the US, dostarlimab is indicated for adult patients with dMMR recurrent or advanced endometrial cancer, as determined by an FDA-approved test, that have progressed on or following prior treatment with a platinum-containing regimen. Dostarlimab is also indicated in the US for patients with dMMR recurrent or advanced solid tumours, as determined by an FDA-approved test, that have progressed on or following prior treatment and who have no satisfactory alternative treatment options. These indications are approved in the US under accelerated approval based on tumour response rate and durability of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

Dostarlimab was discovered by AnaptysBio 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

Dostarlimab 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 EMA Reference Information for a full list of adverse events and the complete important safety information in the EU.

On December 2, 2022 Bio-Thera Solutions, a commercial-stage biopharmaceutical company developing a pipeline of innovative therapies and a pipeline of biosimilars, reported that the company will present two posters at the 2022 San Antonio Breast Cancer Symposium (SABCS) taking place December 6 – 10, 2022 in San Antonio, Texas (Press release, BioThera Solutions, DEC 2, 2022, View Source [SID1234624715]).

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The first poster, entitled "BAT8006, a novel FRα-ADC with strong bystander effect, for the treatment of advanced solid tumor," will present preclinical data and initial phase 1 clinical data that highlight advantages demonstrated by BAT8006 as a potential treatment for patients with solid tumors, such as ovarian cancer and breast cancer. An abstract of the presentation is currently available on the SABCS website.

Presentation details are as follows:

Poster Session:

Session Date and Time:

Thursday, December 8, 7:00 am – 8:15 am

Location:

Poster Area/Exhibition Hall

Poster Board Number:

P4-01-12

The second poster, entitled "BAT8008, a novel Trop-2 ADC with strong bystander effect, for the treatment of Trop-2 positive cancer," will present preclinical data that highlight advantages demonstrated by BAT8008 as a potential treatment for Trop-2 positive cancer patients. An abstract of the presentation is currently available on the SABCS website.

Presentation details are as follows:

Poster Session:

Session Date and Time:

Thursday, December 8, 7:00 am – 8:15 am

Location:

Poster Area/Exhibition Hall

Poster Board Number:

P4-01-32

BAT8006 and BAT8008 are two new ADC assets being developed with Bio-Thera’s next-gen ADC platform that utilizes a systemically stable cleavable linker, a potent Topoisomerase 1 inhibitor (Exatecan) as the payload, and high DARs that takes advantage of the bystander effect to increase efficacy. Other new ADC assets developed using this next-gen ADC platform include BAT8007 (Nectin4-ADC), BAT8009 (B7-H3-ADC) and BAT8010 (Her2-ADC). All of these ADC assets are currently in, or about to begin, Phase 1 clinical trials.

About BAT8006

BAT8006 is an investigational Folate Receptor-alpha-ADC being evaluated in multiple tumor types. Folate Receptor is a naturally occurring receptor that is overexpressed in many types of cancer, including breast cancer and ovarian cancer. BAT8006 is being developed for use as a single agent and in combination with other agents for the treatment of multiple cancers. BAT8006 is currently being evaluated in a Phase 1 clinical trial evaluating the pharmacodynamics and safety of BAT8006 (more information on the Phase 1 clinical trial is available at View Source).

About BAT8008

BAT8008 is an investigational Trop-2-ADC being evaluated in multiple tumor types. Trop-2 is a naturally occurring receptor that is overexpressed in many types of cancer, including triple negative breast cancer and gastric cancer. BAT8008 is being developed for use as a single agent and in combination with other agents for the treatment of multiple cancers. BAT8008 is currently being evaluated in a Phase 1 clinical trial evaluating the pharmacodynamics and safety of BAT8008 (more information on the Phase 1 clinical trial is available at View Source).

On December 2, 2022 Bio-Thera Solutions, a commercial-stage biopharmaceutical company developing a pipeline of innovative therapies and a pipeline of biosimilars, reported that Jin-Chen Yu, SVP, Research will present a talk on BAT8009 (B7-H3-ADC) at the 2nd Annual ADC Target Selection Summit taking place December 6 – 8, 2022 in Boston, MA (Press release, BioThera Solutions, DEC 2, 2022, View Source [SID1234624714]).

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The talk, entitled "A Novel B7-H3 ADC With Strong Bystander Effect Demonstrates Superior Tumor-Inhibition Activity," will present preclinical data that highlight advantages demonstrated by BAT8009 as a potential treatment for cancer patients. BAT8009 is currently being evaluated in a Phase 1 clinical trial.

BAT8009 is a new ADC being developed with Bio-Thera’s next-gen ADC platform that utilizes a systemically stable cleavable linker, a potent Topoisomerase 1 inhibitor (Exatecan) as the payload, and high DARs that takes advantage of the bystander effect to increase efficacy. Other new ADC assets developed using this next-gen ADC platform include BAT8006 (Folate-Receptor-alpha-ADC), BAT8007 (Nectin4-ADC), BAT8008 (Trop2-ADC) and BAT8010 (Her2-ADC). All of these ADC assets are currently in, or about to begin, Phase 1 clinical trials.

About BAT8009

BAT8009 is an investigational B7-H3-ADC being evaluated in multiple tumor types. B7-H3 is a naturally occurring receptor that is overexpressed in many types of cancer, including lung, liver, esophageal and ovarian cancer. BAT8009 is being developed for use as a single agent and in combination with other agents for the treatment of multiple cancers. BAT8009 is currently being evaluated in a Phase 1 evaluating the pharmacodynamics and safety of BAT8009 (more information on the Phase 1 clinical trial is available at View Source).

On December 2, 2022 Focus-X Therapeutics (referred to here as "Focus-X"), a nuclide drug company that was invested in and incubated by Viva Biotech, reported that it has successfully reached an acquisition agreement with Full-Life Technologies Co., Ltd. (referred to here as "Full-Life") (Press release, Focus-X Therapeutics, DEC 2, 2022, View Source [SID1234624713]). Under the terms of the acquisition, Full-Life will acquire Focus-X for US$245 million, including an upfront payment, potential development, regulatory, and sales-based milestone fees, and royalties on commercial sales. The acquisition is expected to close in the first quarter of 2023. When finished, this will be another pre-clinical acquisition of one of Viva’s portfolio companies, after Dogma and Totient, which once again verifies the capabilities of project discovery and the professional post-investment support of Viva’s investment team.

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Focus-X develops targeted radiopharmaceuticals to treat cancer based on its proprietary peptide engineering technology. They completed their angel round in the third quarter of 2020, which was led by Viva. In addition to financial support, Viva also provided Focus-X with comprehensive incubation services to help it realize the transformation from "concept to product."

Dr. Zhixiong Ye, CSO of Viva, stated, "Since investing in and incubating Focus-X in July 2020, Viva has worked closely with Focus-X on the screening and synthesis of peptides, which is an enriching experience for our team. Highly selective peptides can tackle the pain point of peptide-conjugated nuclide drugs – the toxicity caused by ‘healthy tissue distribution’. Viva provides efficient and high-quality screening and synthesis services for Focus-X with the help of its peptide research and development platform. It also assists Focus-X in obtaining multiple high-quality clinical drug candidates."

Dr. Han Dai, CIO and head of Viva BioInnovator, said, "Relying on the founding team’s years of extensive research and accumulation, Focus-X has successfully developed an innovative peptide-drug conjugate (PDC) platform for the coupling of radionuclides in just two years. This development has advanced multiple nuclide-PDC pipelines into PCC and IIT stages, forming synergy with Full-Life Technology’s international layout in R&D, clinical, and supply chain of radiopharmaceutical drugs."

Fa Liu, Ph.D., co-founder and CEO of Focus X, commented, "I am very grateful for the trust and support of Viva and other investment institutions. Within two years, we have achieved breakthroughs and transformations from zero to multiple clinical candidate molecules, some of which have shown very positive early human data. We have accelerated all the processes from verifying scientific hypotheses, transformation, and optimization, to determining clinical candidate molecules through Viva’s peptide and synthetic chemistry capabilities. Full-Life’s integrated platforms will provide the manufacturing technology, logistics, and clinical development expertise to accelerate the development of our compounds as well as expand our discovery efforts."

"The Focus-X acquisition perfectly leverages Full-Life’s radiotechnology and development platform.This deal will bring two development ready compounds, including a lead with initial human data, a robust pipeline and world class peptide discovery capabilities to Full-Life," said Lanny Sun, Co-founder, Chairman and CEO of Full-Life.