On June 23, 2021 HUYABIO International (HUYABIO), the leader in accelerating global development of China’s pharmaceutical innovations, reported the regulatory approval for HBI-8000 monotherapy of relapsed or refractory (R/R) adult T-cell leukemia/lymphoma (ATL) by the Japanese Pharmaceuticals and Medical Devices Agency (Press release, HUYA Bioscience, JUN 23, 2021, View Source [SID1234584297]).

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"Relapsed and/or refractory ATLL carries a grim prognosis with limited treatment options. Data from the registration study of HBI-8000 has demonstrated meaningful disease response despite the advanced stage of disease, and acceptable safety profile, to address an important unmet medical need in this patient population", said Dr. Atae Utsunomiya, honorary hospital director of Imamura General hospital in Japan.

The drug was approved based on data from a Phase 2b study that involved 23 patients with aggressive ATL in Japan. These patients, having few effective treatment options, all had advanced disease either refractory to or relapsed after receiving mogamulizumab. HBI-8000 40mg orally administered twice weekly resulted in disease response in a clinically meaningful proportion of patients with an acceptable safety profile.

Dr. Mireille Gillings, CEO & Executive Chair of HUYABIO said, "This first regulatory approval for our lead oncology drug, HBI-8000, is a major milestone for the Company. The durability and strong immuno- oncology properties of HBI-8000 set the stage for improved cancer treatment of both solid and liquid tumors. Synergy with PD-1/PD-L1 inhibitors hold particular promise for major solid tumor advances."

About HBI-8000
HBI-8000 is an epigenetic immunomodulator approved for the treatment of lymphoma and metastatic breast cancer in China. This oral agent targets class I histone deacetylases (HDAC) and suppresses the expression of the viral oncogene HTLV-I bZIP factor, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) and the inflammasome in ATL cells. Furthermore, HBI-8000 may induce latent viral antigen expression making ATL cells more sensitive to immune cytotoxicity targeting.

On June 23, 2021 AstraZeneca and HUTCHMED reported that its Orpathys (savolitinib) has been granted conditional approval in China to treat patients with non-small cell lung cancer (NSCLC) with MET exon 14 skipping alterations who have progressed following prior systemic therapy or are unable to receive chemotherapy (Press release, AstraZeneca, JUN 23, 2021, View Source [SID1234584265]).

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This approval follows a priority review designation by the Center for Drug Evaluation of China’s National Medical Products Administration (NMPA) and marks the first global regulatory approval for the oral, potent, and highly selective MET tyrosine kinase inhibitor (TKI).

More than a third of the world’s lung cancer patients are in China and, among those with NSCLC, approximately 2-3% have tumours with MET exon 14 skipping alterations, a targetable mutation in the MET gene.1-3 This mutation is more common (13-22%) among patients with pulmonary sarcomatoid carcinoma (PSC), a rare and aggressive subtype of NSCLC usually resistant to chemotherapy.1,4

The approval by the NMPA was based on positive results from a single-arm Phase II trial conducted in China in patients with NSCLC with this mutation, including patients with the PSC subtype. Orpathys demonstrated robust anti-tumour activity based on an independent review of objective response rate (ORR) in the trial’s primary endpoint and its disease control rate (DCR). Continued approval is contingent upon the successful completion of a confirmatory trial in this patient population.

Dave Fredrickson, Executive Vice President, Oncology Business Unit, said: "This approval makes Orpathys the only targeted medicine approved for these biomarker-selected patients in China, and it adds another novel medicine to our already diverse lung cancer portfolio. We are proud that this first-ever regulatory approval of Orpathys is in China, where we have a long-standing commitment to improving patient outcomes and working with the right partners to achieve that goal. Alongside HUTCHMED, we look forward to the continued development of this medicine across a range of cancers where MET alterations and amplification are drivers of tumour growth and treatment resistance."

Christian Hogg, Chief Executive Officer, HUTCHMED, said: "It is with great pleasure that today we announce the first regulatory approval of Orpathys globally, HUTCHMED’s third self-discovered oncology drug to be commercialized. Our collaboration with AstraZeneca in 2011 has been an important driver in the development of this novel targeted oncology drug, involving both a China-based biotech and a global pharmaceutical company. This approval is a testament to the perseverance and scientific ingenuity of this long-standing alliance, and we are hopeful that this is only the beginning of the progress we can achieve for patients with MET-altered tumours."

In the Phase II trial, at a median follow up of 17.6 months, Orpathys demonstrated an ORR of 42.9% (95% confidence interval [CI] 31.1-55.3) and median progression-free survival (PFS) of 6.8 months (95% CI 4.2-9.6) in the overall trial population. PFS was clinically meaningful across subgroups, and ORR results were consistent regardless of prior treatment or tumour histology, including in patients with the PSC subtype (40.0%, 95% CI 21.1-61.3) and patients with other NSCLC subtypes (44.4%, 95% CI 29.6-60.0). DCR in the overall trial population was 82.9% (95% CI 72.0-90.8).

The safety and tolerability profile of Orpathys was consistent with previous trials, and no new safety signals were identified. Most adverse events (AEs) were Grade 1–2 and resolved with dose modification or discontinuation. Grade 3 or higher AEs occurred in 45.7% of patients, and treatment-related serious AEs occurred in 24% of patients. One treatment-related death was reported from tumour lysis syndrome in a patient with PSC.

Results from the Phase II trial were presented during the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) ASCO (Free ASCO Whitepaper)20 Virtual Scientific Program in May 2020, and updated results were published in The Lancet Respiratory Medicine in June 2021.

As part of the joint global development programme with HUTCHMED, Orpathys is being evaluated in combination with Tagrisso and other medicines to address tumour mechanisms of resistance in NSCLC in the ORCHARD and SAVANNAH Phase II trials for the combinations to provide longer duration of benefit, and as a treatment for other MET-driven tumours, including papillary renal cell carcinoma, and gastric and gastroesophageal junction cancers.

NSCLC, PSC and MET aberrations
Lung cancer is the leading cause of cancer death among men and women, accounting for about one-fifth of all cancer deaths.2 Lung cancer is broadly split into NSCLC and small cell lung cancer, with 80-85% classified as NSCLC.5 The majority of NSCLC patients are diagnosed with advanced disease.6

PSC is a rare subtype of NSCLC, comprising 0.3-3% of all lung malignancies.7 Compared with other NSCLC subtypes, PSC patients have a poorer prognosis and limited treatment options.4,8-9

MET is a tyrosine kinase receptor.10 While MET genetic alterations are common in many solid tumours, MET exon 14 skipping alterations are more frequently associated with lung cancer, occurring in approximately 2-3% of patients with NSCLC and 13-22% of patients with PSC.1,4,11 MET amplification or overexpression is one of the mechanisms of acquired resistance to epidermal growth factor receptor (EGFR) TKIs for metastatic EGFR-mutated NSCLC.10

NCT02897479
The single-arm, open-label Phase II trial NCT02897479 assessed the efficacy and safety of Orpathys in the treatment of Chinese patients with locally advanced or metastatic PSC or other NSCLC subtypes with MET exon 14 skipping alterations who progressed on prior treatment or were unable to receive chemotherapy.

Patients were treated with weight-based dosing of Orpathys once-daily oral tablets (600mg/day or 400mg/day for patients weighing less than 50kg). Treatment continued until disease progression, death, intolerable toxicity, or discontinuation. The trial enrolled 70 patients across multiple centres in China. The primary endpoint was ORR, and key secondary endpoints were PFS, DCR and safety assessment.

Orpathys
Orpathys (savolitinib) is an oral, potent, and highly selective MET TKI that has demonstrated clinical activity in advanced solid tumours. It blocks atypical activation of the MET receptor tyrosine kinase pathway that occurs because of mutations (such as exon 14 skipping alterations or other point mutations) or gene amplification.

Orpathys is currently under clinical development for multiple tumour types, including lung, kidney, and gastric cancers, as a single treatment and in combination with other medicines.

AstraZeneca and HUTCHMED collaboration
In 2011, AstraZeneca and HUTCHMED entered a global licensing agreement to jointly develop and commercialise Orpathys. HUTCHMED is responsible for the manufacturing and supply of Orpathys, and AstraZeneca is responsible for its commercialisation in China and worldwide. Sales of Orpathys will be recognised by AstraZeneca.

AstraZeneca in lung cancer
AstraZeneca is working to bring patients with lung cancer closer to cure through the detection and treatment of early-stage disease, while also pushing the boundaries of science to improve outcomes in the resistant and advanced settings. By defining new therapeutic targets and assessing innovative approaches, the Company aims to match medicines to the patients who can benefit most.

The Company’s comprehensive portfolio includes leading lung cancer medicines and the next wave of innovations including Tagrisso (osimertinib) and Iressa (gefitinib); Imfinzi (durvalumab) and tremelimumab; Enhertu (trastuzumab deruxtecan) and datopotamab deruxtecan in collaboration with Daiichi Sankyo; Orpathys (savolitinib) in collaboration with HUTCHMED; as well as a pipeline of potential new medicines and combinations across diverse mechanisms of action.

AstraZeneca is a founding member of the Lung Ambition Alliance, a global coalition working to accelerate innovation and deliver meaningful improvements for people with lung cancer, including and beyond treatment.

AstraZeneca in oncology
AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients.

The Company’s focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyse changes in the practice of medicine and transform the patient experience.

AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death.

On June 23, 2021 Alentis Therapeutics reported that it will present data at the European Association for the Study of the Liver (EASL) International Liver Congress 2021, being held virtually from June 23-26, 2021 (Press release, Alentis Therapeutics, JUN 23, 2021, View Source [SID1234584264]).

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Data to be presented includes research from Alentis and academic collaborators that provides preclinical proof-of-concept in patient-derived cell-based and mouse models of CLDN1-specific mAbs for treatment of advanced liver fibrosis and prevention and treatment of hepatocellular carcinoma (HCC).

Presentations at the Digital International Liver Congress are listed below

Oral Presentation GS-2069: Claudin-1 is a target for treatment of advanced liver fibrosis and cancer prevention

Presenter: Natascha Roehlen, Inserm U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, Strasbourg, France; Université de Strasbourg, Strasbourg, France
Presentation Date and Time: June 24, 2021, 4:00 p.m. CEST

Oral Presentation OS-2190: A humanized Claudin-1 specific monoclonal antibody for treatment of hepatocellular carcinoma

Presenter: Natascha Roehlen, Inserm U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, Strasbourg, France; Université de Strasbourg, Strasbourg, France
Presentation Date and Time: June 25, 2021, 3:15 pm CEST

On August 23, 2021 HUTCHMED (China) Limited ("HUTCHMED" or the "Company") (Nasdaq/AIM: HCM) reported the pricing of its global offering (the "Global Offering") of 104,000,000 new ordinary shares (the "Offer Shares") which comprises an international offering (the "International Offering") and a Hong Kong public offering (the "Hong Kong Public Offering") in connection with a primary listing of its ordinary shares (the "Shares") on the Main Board of the Stock Exchange of Hong Kong Limited (the "SEHK") (Press release, Hutchison China MediTech, JUN 23, 2021, View Source [SID1234586913]).

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The final offer price for both the International Offering and the Hong Kong Public Offering (the "Offer Price") has been set at HK$40.10 per Share, which is equivalent to approximately US$25.82 per American depositary share ("ADS") or £3.70 per Share. Each ADS represents five ordinary shares of the Company. The Company has set the Offer Price by taking into consideration, among other factors, the closing price of the ADSs on the Nasdaq Global Select Market ("Nasdaq") and Shares on the AIM market of the London Stock Exchange on June 22, 2021, the latest trading day before pricing. Subject to approval from the SEHK, the Shares are expected to begin trading on the Main Board of the SEHK on June 30, 2021 under the stock code "13".

The gross proceeds to the Company from the Global Offering, before deducting underwriting fees and the offering expenses, are expected to be approximately HK$4.17 billion. In addition, the Company has granted the international underwriters an over-allotment option, exercisable from the date, expected to be on June 30, 2021, on which the Shares are first listed and from which dealings in the Shares are permitted to take place on the Main Board of the SEHK (the "Listing Date") until 30 days after the last day for lodging applications under the Hong Kong Public Offering, to require the Company to issue up to an additional 15,600,000 new Shares at the Offer Price.

The Company will receive all of the net proceeds from the Global Offering and plans to use the net proceeds from the Global Offering primarily to advance its late-stage clinical programs as well as its pipeline of clinical-stage and preclinical drug candidates, further strengthen its commercialization, clinical, regulatory and manufacturing capabilities, fund potential global business development and strategic acquisition opportunities and for general corporate purposes.

Morgan Stanley Asia Limited, Jefferies Hong Kong Limited and China International Capital Corporation Hong Kong Securities Limited are the joint sponsors for the Global Offering.

Information about the Global Offering
Sales of Shares outside of Hong Kong (other than certain Shares which were sold to investors in reliance on Regulation S or another exemption from the registration requirements of the U.S. Securities Act of 1933) initially offered in the United States and sold outside the United States that may be resold from time to time in the United States are being offered pursuant to an automatically effective shelf registration statement that was previously filed with the U.S. Securities and Exchange Commission (the "SEC"). A preliminary prospectus supplement relating to and describing the terms of the Global Offering was filed with the SEC and is available on the SEC’s website at www.sec.gov. The final prospectus supplement relating to the Global Offering will be filed with the SEC and will be available on the SEC’s website at www.sec.gov. When available, an electronic version of the prospectus supplement and the accompanying prospectus relating to these securities, as filed with the SEC, may be obtained for free by mailing the request to: Morgan Stanley & Co. LLC, 180 Varick Street, 2nd Floor, New York, NY 10014, Attention: Prospectus Department, or E-mail: [email protected]; Jefferies Hong Kong Limited, Email: [email protected]; and China International Capital Corporation Hong Kong Securities Limited, Email: [email protected].

This announcement is not directed to, or intended for distribution or use by, any person or entity that is a citizen or resident or located in any locality, state, country or other jurisdiction where such distribution, publication, availability or use would be contrary to law or regulation or which would require any registration or licensing within such jurisdiction.

The 104,000,000 new Shares to be issued by HUTCHMED pursuant to the Global Offering ("New Shares") will, when issued, be credited as fully paid and will rank pari passu in all respects with the existing ordinary shares of HUTCHMED, including the right to receive all dividends and other distributions declared, made or paid in respect of such Shares after the date of issue of the New Shares.

Application will be made to the London Stock Exchange for the 104,000,000 New Shares to be admitted to the AIM market operated by the London Stock Exchange ("Admission"). It is expected that Admission will become effective at 8:00 a.m. UK time on June 30, 2021.

Following Admission and prior to any exercise of the over-allotment option, the issued share capital of HUTCHMED will consist of 848,515,660 Shares of US$0.10 each, with each Share carrying one right to vote and with no Shares held in treasury. This figure may be used by shareholders as the denominator for the calculations by which they could determine if they are required to notify their interest in, or a change to their interest in, HUTCHMED under the Financial Conduct Authority’s Disclosure Guidance and Transparency Rules. For illustrative purposes only, 848,515,660 Shares would be equivalent to 848,515,660 depositary interests (each equating to one ordinary share) which are traded on AIM or, if the depositary interests were converted in their entirety, equivalent to 169,703,132 ADSs (each equating to five Shares) which are traded on Nasdaq. A further announcement will be made if the over-allotment option is exercised.

This announcement contains inside information for the purposes of Article 7 of Regulation (EU) No 596/2014 (as it forms part of retained EU law as defined in the European Union (Withdrawal) Act 2018).

On June 23, 2021 Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, "Eisai") reported that it has obtained manufacturing and marketing approval for the EZH2 inhibitor "Tazverik Tablets 200 mg" (tazemetostat hydrobromide) in Japan with the indication of relapsed or refractory EZH2 gene mutation-positive follicular lymphoma (only when standard treatment is not applicable) (Press release, Eisai, JUN 23, 2021, View Source [SID1234584266]).

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This approval is based on the results of a multicenter, open-label, single-arm clinical phase II trial (Study 206)1 in Japan conducted by Eisai and other studies2 conducted by Epizyme, Inc. (Headquarters: Massachusetts, United States) outside Japan. Study 206 enrolled patients with EZH2 gene mutation-positive, primarily follicular lymphoma, who had relapsed or were refractory. The primary endpoint of this study was objective response rate (ORR), and secondary endpoints included safety. This study achieved the primary endpoint target and exceeded a prespecified tumor response threshold with statistical significance: ORR in patients with EZH2 mutation-positive relapsed or refractory follicular lymphoma (n=17) was 76.5% (90% confidence interval (CI): 53.9-91.5) as measured by independent review. Treatment-emergent adverse events (incidence of 25% or more) observed in this study were dysgeusia (52.9%), nasopharyngitis (35.3%), lymphopenia (29.4%) and blood creatine phosphokinase increased (29.4%). Eisai will conduct a post-marketing special use results survey (all-case surveillance) in all patients who are administered "Tazverik" until a pre-determined number of patients has been reached in accordance with an approval condition imposed by the MHLW.

Created by utilizing Epizyme’s proprietary product platform, "Tazverik" is a first-in-class small molecule inhibitor of the epigenetic enzyme EZH2. It is one of the histone methyltransferases in the epigenetics-related protein group, and is thought to regulate the expression of cancer-related genes and suppress the growth of cancer cells by specifically targeting EZH2, which contributes to the cancer growth process.3 Eisai is responsible for the development and commercialization of this agent in Japan, while Epizyme, Inc. is responsible for all regions outside of Japan. In the United States, "Tazverik" received accelerated approval for the indication of epithelioid sarcoma in January 2020, and follicular lymphoma in June 2020 (Notes to editors 1).

Follicular lymphoma is a low-grade B-cell lymphoma that accounts for 10-20% of non-Hodgkin’s lymphomas. Follicular lymphoma is generally indolent and sensitive to chemotherapy. However, development of a new treatment strategy is required for follicular lymphoma which still remains difficult to cure, as recurrence often occurs repeatedly. 7-27% of follicular lymphomas are reported to have gain-of-function mutations in the EZH2 gene,4,5 and it is estimated that there are approximately 600 to 2,400 patients with follicular lymphoma with EZH2 gene mutations in Japan. A companion diagnostic test for EZH2 gene mutations, "cobas EZH2 Mutation Test" by Roche Diagnostics K.K. (Headquarters: Tokyo) was approved in May 2021.
　

Eisai aims to make continuous efforts to meet the diversified needs of and increase the benefits provided to patients with cancer, their families, and healthcare professionals, by delivering "Tazverik" as a new treatment option for EZH2 gene mutation-positive follicular lymphoma.