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)
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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."

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C4 Therapeutics Receives Study May Proceed Letter from U.S. FDA to Initiate Phase 1/2 Clinical Trial of CFT1946, an Orally Bioavailable BiDAC™ Degrader, in BRAF-V600 Mutant Solid Cancers

On September 29, 2022 C4 Therapeutics, Inc. (C4T) (Nasdaq: CCCC), a clinical-stage biopharmaceutical company dedicated to advancing targeted protein degradation science to develop a new generation of small-molecule medicines and transform how disease is treated, reported it has received a Study May Proceed Letter from the United States Food and Drug Administration (FDA) to begin a Phase 1/2 trial for CFT1946, an orally bioavailable mutant-selective BiDAC degrader for the treatment of BRAF-V600 mutant solid tumors (Press release, C4 Therapeutics, SEP 29, 2022, View Source [SID1234621555]).

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"The Study May Proceed Letter from the FDA, which marks C4T’s third successful oncology investigational new drug application in less than two years, demonstrates the power of our TORPEDO platform to build an exciting portfolio of degrader medicines that have the potential to transform how diseases are treated," said Andrew Hirsch, president and chief executive officer of C4 Therapeutics. "We designed CFT1946 to be a potent and selective degrader of mutant BRAF-V600, which accounts for approximately 50,000 cancer diagnoses annually. We believe our innovative therapeutic candidate may overcome some limitations of BRAF inhibitor treatments to offer cancer patients the potential for deeper and more durable responses."

The Phase 1/2 clinical trial will primarily investigate safety, tolerability, and anti-tumor activity, with secondary and exploratory objectives to characterize the pharmacokinetic and pharmacodynamic profile of CFT1946. The initial arm of the Phase 1 portion of the study will evaluate CFT1946 as a single agent in patients with BRAF-V600 mutant solid tumors. As the Phase 1 trial progresses, an additional arm of the trial will evaluate CFT1946 in combination with trametinib in patients with BRAF-V600 mutant solid tumors. Following the identification of the recommended dose, the Phase 2 portion of the trial is expected to expand to three investigational arms to evaluate: (1) CFT1946 monotherapy in patients with V600 mutant melanoma or non-small cell lung cancer (NSCLC) after prior BRAF inhibitor treatment; (2) CFT1946 in combination with trametinib in patients with V600 mutant melanoma or NSCLC after prior BRAF inhibitor treatment; and (3) CFT1946 in combination with trametinib in patients with V600 mutant NSCLC who have not previously been treated with a BRAF inhibitor.

Viewpoint Molecular Targeting Announces Transformational Merger

On September 29, 2022 Viewpoint Molecular Targeting, Inc. ("Viewpoint" or the "Company"), a radiopharmaceutical company developing precision lead-212-based α-particle oncology therapeutics and complementary diagnostic imaging agents, reported that it has entered into a definitive agreement to merge with Isoray, Inc (NYSE AMERICAN:ISR), a medical technology company and innovator in seed brachytherapy (Press release, Viewpoint Molecular Targeting, SEP 29, 2022, https://viewpointmt.com/viewpoint-molecular-targeting-announces-transformational-merger/ [SID1234621541]).

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Under the terms of the agreement, a newly formed wholly owned subsidiary of Isoray will merge with and into Viewpoint, with Viewpoint continuing as the surviving corporation and a wholly owned subsidiary of Isoray. At the effective time of the merger, each issued and outstanding share of common stock of Viewpoint will be converted into the right to receive 3.3212 shares of Isoray common stock. Other than cash paid in lieu of fractional shares, there will be no cash consideration paid in connection with the merger. Following completion of the merger, the stockholders of Viewpoint will own 49% of the fully diluted outstanding capital stock of Isoray.

The merger is subject to approval by the shareholders of both Isoray and Viewpoint along with other customary closing conditions including receipt by Isoray of a fairness opinion and any necessary governmental or regulatory approvals. Upon closing, the size of Isoray’s board of directors will increase to 5 with 2 directors to be designated by Viewpoint and 3 directors to be designated by Isoray. Lori Woods will be one of the directors appointed by Isoray and will serve as the chairperson. Thijs Spoor, Viewpoint’s current CEO, will be one of the directors appointed by Viewpoint and will serve as Isoray’s CEO.

Additional details along with the merger agreement can be found in Isoray Inc.’s 8-K which was filed with the Securities and Exchange Commission.

Viewpoint Molecular Targeting CEO Thijs Spoor said, "I believe the combination of Isoray, and Viewpoint presents a unique platform company in the precision radiation therapy market. The companies’ shared vision of treating cancer from the inside out and pioneering effective, personalized cancer fighting therapies that aim to minimize unwanted side effects presents a compelling proposition for patients, clinicians, and investors. At Viewpoint Molecular Targeting, we believe this proposed merger brings together two innovative medical technology companies to create a dynamic new force to make cancer care more personalized."

Isoray CEO Lori Woods commented, "The proposed merger with Viewpoint represents a culmination of a long and rigorous process. Throughout our strategic evaluations of opportunities, we have examined the evolving therapies and approaches that signal the future of cancer treatments. In line with our focus on ‘treating cancer from the inside out,’ one therapeutic area that has been of great interest to us is targeted alpha therapy. We have been following it closely and we believe that it has significant potential. It is our belief that the merger with Viewpoint Molecular Targeting represents a solid fit with Isoray’s existing business. It allows us to pursue an enhanced path forward in evolving the technology that we believe will have a significant impact on the future of cancer treatments and the company as we build on our complementary strengths."

CRISPR Therapeutics to Present at the BMO Biopharma Spotlight Series: Gene Editing and Therapy

On September 29, 2022 CRISPR Therapeutics (Nasdaq: CRSP), a biopharmaceutical company focused on creating transformative gene-based medicines for serious diseases, reported that members of its senior management team are scheduled to participate in the BMO Biopharma Spotlight Series: Gene Editing and Therapy on Thursday, October 6, 2022, at 9:00 a.m. ET (Press release, CRISPR Therapeutics, SEP 29, 2022, View Source [SID1234621557]).

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A replay of the webcast will be archived for 14 days following the presentation on the "Events & Presentations" page in the Investors section of the Company’s website at View Source

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]).

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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.