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Chugai Files New Drug Application in Japan for Fixed-Dose Subcutaneous Combination of Pertuzumab and Trastuzumab for HER2-Positive Breast and Colorectal Cancer

On September 29, 2022 Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) reported that it filed a new drug application for RG6264 today with the Ministry of Health, Labour and Welfare (MHLW) for the treatment of HER2-positive breast cancer, and HER2-positive colorectal cancer that has progressed after chemotherapy (Press release, Chugai, SEP 29, 2022, View Source [SID1234621539]). RG6264 is a fixed-dose subcutaneous combination of antineoplastic agent / anti-HER2 humanized monoclonal antibody, Perjeta [generic name: pertuzumab (genetical recombination)] and anti-HER2 humanized monoclonal antibody / antineoplastic agent, Herceptin [generic name: trastuzumab (genetical recombination)].

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The fixed-dose subcutaneous combination contains the same monoclonal antibodies as Perjeta, Herceptin, and vorhyaluronidase alfa (genetical recombination) in a single vial. Hyaluronidase, an enzyme that breaks down hyaluronic acid, is considered to increase dispersion and absorption of the antibodies. It takes 150 minutes for a sequential infusion of a loading dose of Herceptin and Perjeta using intravenous formulations, excluding follow-up observation, and 60-150 minutes for maintenance infusions.1,2,3) By comparison, in FeDeriCa study it took approximately eight minutes to infuse a loading dose of RG6264 and five minutes for maintenance infusions. The safety of RG6264 shown in FeDeriCa study was comparable to the intravenous administration of Perjeta and Herceptin. In the study, alopecia, nausea, diarrhea, and anemia were reported as adverse events.4) Another clinical study (PHranceSCa study) showed that 85% of patients (N=136/160) evaluated in the study preferred RG6264 injection to the separate IV administration of Perjeta and Herceptin.5)

"We are very pleased that the regulatory application has been filed for the subcutaneous formulation of the combination therapy of Perjeta and Herceptin, the standard therapy for HER2-positive breast cancer," said Chugai’s President and CEO, Dr. Osamu Okuda. "Reduction of administration time is expected to offer better convenience for patients and to reduce the burden on healthcare professionals. In order to deliver new value to patients and healthcare professionals as soon as possible, we will work together with Roche to obtain approval."

The application is based on the results of the global phase III FeDeriCa study and an overseas phase II PHranceSCa study. FeDeriCa study evaluated the pharmacokinetics, efficacy, and safety of RG6264 with patients with HER2-positive breast cancer. PHranceSCa study examined patient preference and satisfaction with subcutaneous administration of RG6264 in HER2-positive breast cancer. Chugai is responsible for the development of RG6264 in Japan and has been participating in FeDeriCa study.

[Reference information]
Roche’s fixed-dose subcutaneous combination of Perjeta and Herceptin comparable to intravenous formulations in people with HER2-positive breast cancer (Press release issued by Roche on December 12, 2019)
View Source

About FeDeriCa study4)
FeDeriCa is an international, multi-center, two-arm, randomized, open-label, phase III study evaluating the pharmacokinetics, efficacy and safety of subcutaneous injection of the fixed-dose combination of Perjeta and Herceptin in combination with chemotherapy, compared with standard intravenous infusions of Perjeta and Herceptin in combination with chemotherapy in 500 people with HER2-positive early breast cancer who are being treated in the neoadjuvant (before surgery) and adjuvant (after surgery) settings. The primary endpoint of the study is minimum levels of Perjeta in the blood during a given dosing interval (Ctrough). Secondary endpoints include safety; minimum levels of Herceptin in the blood during a given dosing interval (Ctrough); and pathological complete response (pCR) in the breast and axilla.

About PHranceSCa study5)
PHranceSCa is an overseas phase II randomized clinical study to evaluate patient preference and satisfaction for the fixed-dose combination of Perjeta and Herceptin for subcutaneous injection in 140 patients with HER2-positive early breast cancer. The primary endpoint is patient’s preference for this drug based on responses to the Patient Preference Questionnaire (PPQ). Secondary endpoints include patient satisfaction with this drug and Perjeta and Herceptin intravenous formulations as measured by the Therapy Administration Satisfaction Questionnaire (TASQ), and patient’s selection of this drug during continued treatment.

About Perjeta
Perjeta is a humanized monoclonal antibody that targets human epidermal growth factor receptor type 2 (HER2), which is involved in the growth of tumor cells. Perjeta in combination with Herceptin blocks the HER-signaling system more extensively. The drug was launched in 2013 for "inoperable or recurrent HER2-positive breast cancer." The indication was amended as "HER-2 positive breast cancer," after obtaining regulatory approval for the additional indication of "neoadjuvant and adjuvant therapy in HER2-positive breast cancer" in 2018. In addition, it was approved for the indication of "advanced or recurrent HER2-positive colon cancer or rectal cancer not amenable to curative resection that has progressed after cancer chemotherapy" in 2022.

About Herceptin
Herceptin, like Perjeta, is a humanized monoclonal antibody that targets human epidermal growth factor receptor type 2 (HER2), which is involved in the growth of tumor cells. Herceptin was launched in 2001 for "metastatic breast cancer overexpressing HER2." Thereafter, the indication was changed to "Breast cancer overexpressing HER2" in 2011 based on the approved postoperative drug therapy and the additional approval of preoperative drug therapy based on a public knowledge-based application. In 2011, it was approved for the treatment of patients with "advanced or recurrent gastric cancer overexpressing HER2 not amenable to curative resection", in 2021 for "advanced or recurrent HER2-positive salivary gland cancer not amenable to curative resection" and in 2022 for "advanced or recurrent HER2-positive colon cancer or rectal cancer not amenable to curative resection that has progressed after cancer chemotherapy."

Trademarks used or mentioned in this release are protected by law.

Almirall and Simcere enter into a licensing agreement for IL-2-mu-Fc

On September 29, 2022 Almirall S.A. (BME: ALM), a global biopharmaceutical company focused on skin health, and Simcere Pharmaceutical Group（2096.HK), an innovation and R&D-driven pharmaceutical company; reported that they have entered into an exclusive licensing agreement for Simcere’s IL-2 mutant fusion protein (IL-2 mu-Fc) autoimmune drug candidate, SIM0278 (Press release, Almirall, SEP 29, 2022, View Source [SID1234621523]).

Under the agreement, Almirall will be granted an exclusive right to develop and commercialise SIM0278 for all indications outside of the Greater China region (Mainland China, Hong Kong, Macau and Taiwan). Simcere will retain all rights to develop and commercialise SIM0278 within Greater China.

Within the terms of the agreement, Simcere will receive a $15 million upfront payment and up to US$492 million in development and commercial milestone payments considering successful achievements in several indications, with an important part as sales milestones, as well as up to low double-digit tiered royalties based upon future global sales.

"We are very excited to have reached a collaborative agreement with Almirall for the development of SIM0278. This innovative IL-2 mutein is one important molecule of our immune-rebalancing strategy for autoimmune diseases," said Renhong Tang, Ph.D., Co-CEO of Simcere. "SIM0278 is one of the key molecules developed based on Simcere’s in-house protein engineering platform. This partnership also marks a milestone for Simcere’s globalisation effort. We look forward to closely working with Almirall to demonstrate the clinical value of SIM0278."

"At Almirall, we always look for new opportunities to strengthen our R&D pipeline. That is why we are very pleased to close this new development and commercialisation agreement with Simcere," stated Karl Ziegelbauer, Ph.D., Almirall’s Chief Scientific Officer. "SIM0278 has great potential to treat a broad spectrum of immunological diseases, and we expect that its development will allow us to reinforce our biologic pipeline and our leading position in Medical Dermatology."

About SIM0278

SIM0278 is an interleukin 2 mutant fusion protein (IL-2 mu-Fc) that activates regulatory T cells developed in-house by utilizing Simcere’s protein engineering platform. This IND ready subcutaneous injection will potentially be developed to treat various autoimmune diseases. SIM0278 exhibits improved PK profile and selective activation of Treg cells with no activation of effector T cells or NK cells to restore immune balance which has been demonstrated in multiple preclinical disease models.

The IND application of Biosyngen BRG01 Therapy was accepted by CDE

On September 28, 2022 Biosyngen reported The IND application of BRG01 Therapy has been accepted for review by the Center for Drug Evaluation, China (CXSL2200487)（View Source; (Press release, BioSyngen, SEP 28, 2022, View Source [SID1234621630]). BRG01 Therapy is autologous T cell therapy for relapsed/metastatic nasopharyngeal cancer (NPC) treatment. The principle of the autologous T cell therapy is to genetically modify patients’ own T cells to express the additional receptor for Epstein-Barr virus (EBV) antigen recognition and T cell activation upon EBV+ tumor cell engagement.

Dr. Han Deping, CEO and CMO of Biosyngen, said, "The acceptance of IND filing for BRG01 Therapy marks a milestone in nasopharyngeal cancer treatment. With its good safety and preliminary efficacy profile, BRG01 Therapy brings hope and gives a second chance to cancer patients and their families."

EBV is a human herpesvirus and has infected ~95% of population worldwide. It has been listed as Group 1 carcinogen ("Carcinogenic to humans") by World Health Organization (WHO) and proved to be associated with a range of diseases including nasopharyngeal cancer, EBV-positive gastric cancers, lymphoma and lymphoproliferative diseases. As one of the most common head and neck tumors, nasopharyngeal cancer, an epithelial carcinoma arising from the nasopharyngeal mucosal lining, is closely related to EBV infection. According to WHO, in 2020, there were about 133,000 new cases of nasopharyngeal cancer worldwide, 50% of which was diagnosed in China. South China provinces like Guangdong and Guangxi provinces makes up for more than 60% of nasopharyngeal cancer patient population.

BRG01 Therapy developed by Biosyngen is an engineered T cell therapy, also known as a type of adoptive immune cell therapy for nasopharyngeal cancer treatment. Patients’ T cells were isolated and genetically modified in the GMP-compliant facility to enhance their ability to recognize and attack specific antigens on cancer cells. The modified T cells are then expanded ex vivo and infused back to the patient. The infused T cells could bind to the specific antigen on the cancer cells to mediate tumor killing.

About Biosyngen

With R&D powered by scientists from Singapore, China, Germany, Australia, France, and America, Biosyngen is dedicated to give cancer patients a second chance by developing first-in-class and best-in-class innovative immunotherapies. Aiming for the global market with dual R&D centers and GMP facilities set in Singapore and China, Biosyngen owns a product portfolio with potential global market of more than 50 billion USD.

Biosyngen possesses exclusive licenses and patented therapies targeting multiple solid tumors and hematological malignancies including nasopharyngeal cancer, gastric cancer, lymphoma and posttransplant lymphoproliferative disorders. We collaborate closely with the world’s leading biomedical research and clinical institutes including A*STAR, Helmholtz Zentrum München, Hannover Medical School, Sun Yat-Sen University Cancer Center to advance our R&D process and conduct clinical trials in Singapore, Australia and China.

Utilizing our strong R&D capability and translational medicine platform, we have been able to engage the end-to-end cycle of drug development including lead identification, preclinical studies cell production and quality control, regulatory filing and clinical studies, thus integrating R&D, manufacturing and commercialization.

Valneva Announces Launch of Approximately $40 Million in a Proposed Global Offering of American Depositary Shares and Ordinary Shares

On September 28, 2022 Valneva SE (Nasdaq: VALN; Euronext Paris: VLA) (the "Company"), a specialty vaccine company, reported its intention to issue and sell, subject to market conditions, approximately $40 million of its ordinary shares in a global offering to specified categories of investors comprised of (i) a public offering of its American Depositary Shares ("ADSs"), each representing two ordinary shares, in the United States (the "U.S. Offering") and (ii) a concurrent private placement of its ordinary shares in certain jurisdictions outside of the United States (the "European Private Placement" and together with the U.S. Offering, the "Global Offering") (Press release, Valneva, SEP 28, 2022, View Source [SID1234621556]).

Goldman Sachs, Jefferies, Guggenheim Securities and Bryan, Garnier & Co. are acting as joint bookrunners for the Global Offering.

All securities to be sold in the Global Offering will be offered by the Company. The ADSs are listed on the Nasdaq Global Select Market under the symbol "VALN," and the Company’s ordinary shares are listed on the regulated market of Euronext in Paris ("Euronext") under the symbol "VLA."

The offering price per ADS in U.S. dollars and the corresponding offering price per ordinary share in euros, as well as the number of ADSs and ordinary shares sold in the Global Offering, will be determined following a book building process commencing immediately. The price per ordinary share (and corresponding offering price per ADS) will be at least equal to the weighted average price of the Company’s ordinary shares on Euronext over a period, chosen by the Company’s Management Board, of between three (3) and ninety (90) consecutive trading days preceding the determination of the offering price, reduced by a maximum discount of 15%, if applicable.

The ADSs and/or ordinary shares will be issued through a capital increase without shareholders’ preferential subscription rights and for the benefit of a specified category of persons within the meaning of Article L.225-138 of the French Commercial Code (Code de commerce) and pursuant to the 24th resolution of the Company’s annual combined general meeting held on June 23, 2022. Under the authority granted by the shareholders in the 24th resolution, the ordinary shares and ADSs may only be purchased initially by (i) natural persons and legal entities, including companies, trusts or investment funds, organized under French or foreign law, that routinely invest in the pharmaceutical, biotechnological or medical technology sector; and/or (ii) companies, institutions or entities of any type, French or foreign, that do a significant part of their business in the pharmaceutical, cosmetic, chemical or medical devices and/or technologies or research in these sectors. In order to purchase ordinary shares and/or ADSs in the Global Offering, potential investors will be required to execute and provide to the Underwriters an investor letter representing that they satisfy the foregoing investor criteria.

The European Private Placement will be open only to qualified investors as such term is defined in article 2(e) of Regulation (EU) 2017/1129 of the European Parliament and of the Council of June 14, 2017.

The closing of the U.S. Offering and the European Private Placement will occur simultaneously, will be conditioned on each other and are expected to occur on the third trading day after the final pricing and allocation of the Global Offering. The underwriting agreement to be entered into among the Company and the underwriters for the Global Offering (the "Underwriters") will not constitute a performance guarantee (garantie de bonne fin) within the meaning of Article L.225-145 of the French Commercial Code.

The Global Offering will commence immediately and the Company plans to announce the result of the Global Offering as soon as practicable after pricing thereof in a subsequent press release. The Company expects to use the net proceeds from the Global Offering to finance the co-development and marketing of its vaccine candidate against Lyme disease (VLA15), to finance the development and marketing of its vaccine candidate against the chikungunya virus (VLA1553), to finance the development of two of its preclinical vaccine candidates, VLA1554 and VLA2112, and the remainder, if any, for working capital and for general corporate purposes.

Bpifrance Participations S.A., which is an existing shareholder, has indicated an interest in purchasing up to an aggregate of €5.0 million of the ordinary shares in the Global Offering at the offering price. However, because indications of interest are not binding agreements or commitments to purchase, the Underwriters may determine to sell fewer or no ordinary shares in the Global Offering to Bpifrance Participations S.A., or Bpifrance Participations S.A. may determine to purchase fewer or no ordinary shares in the Global Offering. The representative of Bpifrance Participations S.A. to the Company’s Supervisory Board (Conseil de Surveillance) did not take part in the vote on the decisions (relating to the approval for the launch of the global offering and for the delegation of authority) at the meeting of the Supervisory Board of Directors (Conseil de Surveillance) held on September 24, 2022.

A shelf registration statement on Form F-3 relating to the ADSs and ordinary shares in the Global Offering was filed with the U.S. Securities and Exchange Commission ("SEC") on August 12, 2022 and was declared effective on August 19, 2022. This press release does not constitute an offer to sell or the solicitation of an offer to buy securities in any jurisdiction, and shall not constitute an offer, solicitation or sale in any jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of that jurisdiction. The securities sold will not be part of a public offering in France. The registration statement, including the prospectus and a preliminary prospectus supplement, can be accessed by the public on the website of the SEC.

The securities referred to in this press release will be offered in the United States only by means of a prospectus approved by the SEC. When available, copies of the preliminary prospectus relating to and describing the terms of the Global Offering may be obtained from: Goldman Sachs & Co. LLC, Attn: Prospectus Department, 200 West Street, New York, New York 10282, telephone: 866-471-2526, facsimile: 212-902-9316, e-mail: [email protected] or Jefferies LLC, Attention: Equity Syndicate Prospectus Department, 520 Madison Avenue, 2nd Floor, New York, NY 10022, or by telephone at +1 877 821 7388 or by email at [email protected].

Application will be made to list the new ordinary shares to be issued pursuant to the Global Offering on the regulated market of Euronext in Paris pursuant to a listing prospectus (the "Listing Prospectus") subject to the approval by the Autorité des Marchés Financiers ("AMF") and comprising (i) the 2021 universal registration document filed with the AMF on March 23, 2022 (document d’enregistrement universel 2021) under number D. 22-0140 (the "2021 URD"), as completed by an amendment to the 2021 URD expected to be filed with the AMF on September 30, 2022 (the "Amendment") and (ii) a securities note (Note d’opération) (the "Securities Note"), including (iii) a summary of the prospectus. Copies of the Company’s 2021 URD, as amended, will be available free of charge on the Company’s website. The Listing Prospectus will be published on the Company’s website and on the AMF’s website (www.amf-france.org).

Xuanzhu Biopharm, a Sihuan Subsidiary, Files to Raise $345 Million in Shanghai STAR IPO

On September 28, 2022 Xuanzhu Biopharm, a novel drug subsidiary of Sihuan Pharm based in Jinan, reported that it has filed for an IPO on the Shanghai STAR Exchange that would raise $345 million (Press release, Xuanzhu Biopharmaceutical, SEP 28, 2022, View Source [SID1234621540]). Now 20 years old, Xuanzhu has developed a portfolio of more than 25 small molecule and biologic candidates, including two NDA stage products. The company has built a 400-member team led by returnee scientists that develops new drugs through its own R&D without depending on in-licensings or CROs. Earlier this year, Xuanzhu completed a $96 million Series B financing.