On March 14, 2022 Sanofi reported The Phase 2 AMEERA-3 clinical trial evaluating amcenestrant, an investigational optimized oral selective estrogen receptor degrader (SERD), did not meet its primary endpoint of improving progression-free survival (PFS) as assessed by an independent central review (Press release, Sanofi, MAR 14, 2022, View Source [SID1234610015]). The trial evaluated amcenestrant as monotherapy compared to endocrine treatment of physician’s choice in patients with locally advanced or metastatic estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer who progressed on or after hormonal therapies. No new safety signals were identified and the safety profile of amcenestrant in AMEERA-3 was consistent with earlier studies.

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John Reed, MD, PhD
Head of Research and Development at Sanofi
"This Phase 2 trial evaluated amcenestrant as a monotherapy in a patient population with advanced disease where limited treatment options remain. While we are disappointed with the AMEERA-3 results, we continue to investigate amcenestrant in patients with earlier stages of breast cancer with different tumor profiles and where different standard of care treatments are used."

Sanofi will continue to assess data from the AMEERA-3 trial and work with investigators on the publication of the full results. The ongoing clinical trial program for amcenestrant continues as planned, including AMEERA-5 and AMEERA-6.

Amcenestrant is an optimized oral SERD that binds to the estrogen receptors (ER) in breast cancer cells to inhibit their normal function and trigger degradation so they can no longer be used by tumor cells to grow. Amcenestrant is currently under clinical investigation and its safety and efficacy have not been evaluated by any regulatory authority.

About the AMEERA-3 trial

AMEERA-3 was an open-label, Phase 2 randomized trial evaluating the efficacy and safety of amcenestrant as a monotherapy compared to single-agent endocrine treatment of the physician’s choice in patients with ER+, HER2- locally advanced or metastatic breast cancer with prior exposure to hormonal therapies. The primary objective of AMEERA-3 was to determine whether amcenestrant improved PFS assessed by an independent central review compared to endocrine monotherapy. The key secondary efficacy endpoint was overall survival and other secondary endpoints were objective response rate, disease control rate, clinical benefit rate and duration of response. The study also compared the overall safety profile in the two treatment arms and evaluated health-related quality of life in the two treatment arms based on patient-reported outcomes.

About the amcenestrant clinical program

The comprehensive development program for amcenestrant has been designed to evaluate its potential as an oral endocrine backbone therapy across treatment lines, including: as a single agent in second-line or later lines of treatment of ER+/HER2- metastatic breast cancer (MBC) (AMEERA-3), in combination with palbociclib in the first-line treatment of ER+/HER2- MBC (AMEERA-5), and to explore its potential in early-stage breast cancer patients in the adjuvant setting (AMEERA-6). Initiated in late 2020, the Phase 3 AMEERA-5 clinical trial is now fully enrolled. The Phase 3 AMEERA-6 trial, in partnership with the Breast International Group (BIG), the European Organization for Research and Treatment of Cancer (EORTC), and the Alliance Foundation Trials (AFT) is now enrolling.

On March 13, 2022 Everest Medicines (HKEX 1952.HK), a biopharmaceutical company focused on developing and commercializing transformative pharmaceutical products to address critical unmet needs in Asia Pacific markets, reported that it has entered into a license agreement with Calliditas Therapeutics AB (Nasdaq: CALT, Nasdaq Stockholm: CALTX) to develop and commercialize NEFECON for the treatment of primary IgA nephropathy (IgAN) in South Korea, expanding its license in addition to rights held in Greater China and Singapore (Press release, Everest Medicines, MAR 13, 2022, View Source [SID1234610010]). The deal signals the Company’s latest efforts to further enhance its international commercial footprint.

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"We’re thrilled to strengthen our partnership with Calliditas by extending our license agreement to include South Korea and working towards our shared vision of developing and commercializing NEFECON as a potential novel therapy for the treatment of IgAN globally," said Kerry Blanchard, MD, PhD, Chief Executive Officer of Everest Medicines. "While primary IgAN is more common in Asia than elsewhere in the world, there are no established treatments for patients living with the chronic condition, underscoring the significant and urgent unmet need for innovative medicines."

"South Korea is the third largest pharmaceutical market in the Asia Pacific region —after China and Japan—and represents tremendous opportunity," said Kevin Yong Guo, Chief Commercial Officer of Everest Medicines. "South Korea’s sophisticated healthcare model enables innovative medicines such as NEFECON to have a higher potential likelihood of healthcare coverage once approved. We look forward to working closely with all contributing parties to bring NEFECON to patients living with IgAN in South Korea as quickly as possible."

"We continue to have a fruitful and positive collaboration with Everest and are delighted that we have come to an agreement also around South Korea," said CEO Renée Aguiar-Lucander of Calliditas.

In the coming months, Everest Medicines will collaborate with the Ministry of Food and Drug Safety of South Korea to prepare regulatory filings and a New Drug Application (NDA) for NEFECON for the treatment of primary IgAN.

Under the terms of the agreement, Calliditas receives an initial upfront payment of USD$3 million at signing of the agreement.

About NEFECON

NEFECON (approved in the United States under accelerated approval under another trade name) is an oral, delayed release formulation of budesonide, a corticosteroid with potent glucocorticoid activity and weak mineralocorticoid activity that undergoes substantial first pass metabolism. NEFECON was designed as a 4 mg delayed release capsule and is enteric coated so that it would remain intact until it reaches the ileum. Each capsule contains coated beads of budesonide that target mucosal B-cells present in the ileum, including the Peyer’s patches, which are responsible for the production of galactose-deficient IgA1 antibodies (Gd-Ag1) causing IgA nephropathy. It is unclear to what extent NEFECON’s efficacy is mediated via local effects in the ileum vs systemic effects. In June 2019, Everest Medicines entered into an exclusive, royalty-bearing license agreement with Calliditas, which gives Everest Medicines exclusive rights to develop and commercialize NEFECON in Mainland China, Hong Kong, Macau, Taiwan and Singapore. The agreement was extended in March 2022 to include South Korea as part of Everest Medicine’s territories.

About Primary Immunoglobulin A Nephropathy

Primary immunoglobulin A nephropathy (IgA nephropathy or IgAN or Berger’s Disease) is a progressive, chronic autoimmune disease that attacks the kidneys and occurs when galactose-deficient IgA1 are recognized by autoantibodies, creating IgA1 immune complexes that become deposited in the glomerular mesangium of the kidney.1,2 This deposition in the kidney can lead to progressive kidney damage and potentially a clinical course resulting in end- stage renal disease. IgAN most often develops between late teens and late 30s.2,3

On March 13, 2022 InnoCare Pharma (HKEX: 09969), a leading biopharmaceutical company, reported that the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) accepted a supplemental New Drug Application (sNDA) for Bruton’s tyrosine kinase (BTK) inhibitor orelabrutinib for the treatment of patients with relapsed or refractory Waldenström’s Macroglobulinemia (R/R WM) b(Press release, InnoCare Pharma, MAR 13, 2022, View Source [SID1234610009]).

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"According to the evaluation of the Independent Review Committee (IRC) and the principal investigators, the treatment of R/R WM patients with orelabrutinib at a dose of 150mg once a day reached the primary end point, showing encouraging efficacy, which is expected to improve with the extension of treatment time," said Professor Daobin Zhou, Director of Hematology Department of Peking Union Medical College Hospital. "Meanwhile, orelabrutinib is well tolerated with safety profile in the treatment of WM patients. The incidence of adverse events, especially off-target related serious adverse events, is significantly lower in the clinical trial."

Dr. Jasmine Cui, Co-founder, Chairwoman and CEO of InnoCare said, "WM poses a threat to patients’ lives. We are encouraged that NMPA has accepted the supplemental New Drug Application for orelabrutinib in the treatment of R/R WM. This sNDA includes 47 patients from 16 clinical centers in China. We hope that orelabrutinib will bring a novel treatment option to R/R WM patients."

On December 25, 2020, orelabrutinib received approval from NMPA in two indications: the treatment of patients with relapsed/refractory chronic lymphocytic leukemia (CLL) /small lymphocytic lymphoma (SLL), and the treatment of patients with relapsed/refractory mantle cell lymphoma (MCL).

About Waldenström’s Macroglobulinemia

Waldenström’s macroglobulinemia is a relatively slow-growing lymphoma characterized by the invasion of bone marrow by lymphoplasmacytic cells secreting monoclonal immunoglobulin M (IgM). The disease usually affects older adults and is primarily found in the bone marrow, although it may also impact lymph nodes and the spleen.

About Orelabrutinib

Orelabrutinib is a highly selective BTK inhibitor developed by InnoCare for the treatment of cancers and autoimmune diseases.

On Dec. 25 2020, orelabrutinib received approval from the China National Medical Products Administration (NMPA) in two indications: the treatment of patients with relapsed/refractory chronic lymphocytic leukemia (CLL) /small lymphocytic lymphoma (SLL), and the treatment of patients with relapsed/refractory mantle cell lymphoma (MCL). At the end of 2021, orelabrutinib was included into National Reimbursement Drug list to benefit more lymphoma patients.

In addition to the approved indications, multi-center, multi-indication clinical trials are underway in the US and China with orelabrutinib as monotherapy or in combination therapies.

Orelabrutinib was granted as Breakthrough Therapy Designation for the treatment of r/r MCL by U.S. Food and Drug Administration (FDA).

Attributed to its excellent selectivity and clinical safety profiles, orelabrutinib is also evaluated in the global phase II studies for the treatment of Multiple Sclerosis (MS), phase II clinical trials for the treatment of Systemic Lupus Erythematosus (SLE) and Primary Immune Thrombocytopenia (ITP) in China.

On March 11, 2022 InnoCure Therapeutics (hereinafter referred to as InnoCure), a new drug development bio-venture, reported the company has completed Series A funding (Press release, InnoCure Therapeutics, MAR 11, 2022, View Source;mode=view&idx=6&sk=&sw=&offset=20&category= [SID1234651741]). Four investment institutions participated and successfully raised a total of 5.5 billion won. Based on this funding, it plans to secure leading substances for preclinical chronic myeloid leukemia treatment, Parkinson’s disease, and RAS-specific mutant protein targets.

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According to the financial investment industry on the 19th, InnoCure raised 5.5 billion won in funds by issuing redeemable convertible preferred stocks. The four institutions that participated in InnoCure’s Series A funding are Starset Investment, Laguna Investment, Suin Investment, and G&Tech Venture Investment.

InnoCure is seeking to be listed on KOSDAQ in 2024 and aims to IPO through a technology special case method when the global clinical entry of three or more products becomes visible.

InnoCure is a bio venture that develops new drugs using the next-generation protein degradation mechanism PROTAC (Proteolysis-Targeting Chimaera) technology. It was founded in January 2018 by CEO Yoo Hye-dong, who participated in the development of new drugs such as the development of alternative drugs for the nano-anticancer drug Abraxane at Celgene.

Based on Series A funding, InnoCure plans to complete preclinical trials for the T315I mutation treatment for chronic myeloid leukemia using PROTAC technology by mid-2022. It is also focusing on securing a leading substance that selectively decomposes RAS-specific mutant proteins that were difficult to approach with small-molecule inhibitor development methods.

PROTAC is an innovative technology that can fundamentally decompose undruggable target proteins that were difficult to approach with existing small-molecule compound methods. PROTAC’s catalytic function is used to achieve high therapeutic effects with small doses, reduce side effects, and overcome resistance to existing treatments, so it is being used in the development of cancer or intractable disease treatments.

On March 11, 2022 Cannabics Pharmaceuticals Inc. (the "Company") reported that it entered into a forbearance agreement (the "Agreement") with an institutional investor (the "Investor") relating to that certain Senior Secured Promissory Note in the original principal amount of $1,375,000 due on December 21, 2021 (the "February Note") (Filing, 8-K, Cannabics Pharmaceuticals, MAR 11, 2022, View Source [SID1234610151]). The February Note was issued by the Company to the Investor in connection with that certain Securities Purchase Agreement dated as of December 16, 2020, and amended as of February 22, 2021.

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Pursuant to the Agreement, the Investor, through May 7, 2022 (the "Forbearance Period"), agreed to forbear from exercising any rights and remedies against the Company related to the outstanding payments under the February Note and to waive certain other defaults under the February Note and related rights pursuant to the Registration Rights Agreement entered into in December 2020 between the Company and the Investor (the "Registration Rights Agreement"). This description of the Agreement does not purport to be complete and is qualified in its entirety by reference to the form of Forbearance Agreement filed as Exhibit 10.1 to this report and is incorporated herein by reference.

As previously described in a Form 8-K filed with the Securities and Exchange Commission on February 17, 2022, on February 15, 2022 the Company entered into a forbearance agreement with the Investor relating to the February Note pursuant to which the Investor had agreed to forbear, through March 7, 2022, from exercising any rights and remedies against the Company related to the outstanding payments under the February Note and to waive certain other defaults under the February Note and related rights pursuant to the Registration Rights Agreement.