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EISAI ENTERS INTO COMMERCIALIZATION AND DISTRIBUTION AGREEMENT WITH GILEAD FOR JAK INHIBITOR FILGOTINIB IN ASIA

On December 20, 2021 Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, "Eisai") reported it has entered into an agreement with Gilead Sciences, Inc. (Headquarters: Foster City, California, "Gilead") for the commercialization and distribution of filgotinib (generic name, product name: Jyseleca ), an oral, JAK1 preferential inhibitor for indications of rheumatoid arthritis (RA), ulcerative colitis, and Crohn’s disease in Asia (South Korea, Taiwan, Hong Kong and Singapore) (Press release, Eisai, DEC 20, 2021, View Source [SID1234597411]). In December 2019, Eisai signed a partnership agreement with Gilead Sciences K.K. (Headquarters: Tokyo), a Japanese subsidiary of Gilead, for the distribution and co-promotion of filgotinib in Japan.

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Under the terms of the new agreement, Eisai will obtain an exclusive marketing right for filgotinib in South Korea, Taiwan, Hong Kong and Singapore from Gilead. Gilead has received approval for the treatment of RA in Taiwan and has applied for approval of filgotinib for the treatment of RA in South Korea. Following approvals, Eisai will take over the manufacturing and marketing licenses for filgotinib from Gilead in South Korea and Taiwan. In Hong Kong and Singapore, Eisai will apply for approval for filgotinib. With this agreement, Eisai will pay Gilead a contractual up-front payment, as well as regulatory milestones and sales milestones.

Filgotinib is a once-daily, oral, JAK1 preferential inhibitor. In Japan, filgotinib has been approved for the treatment of rheumatoid arthritis (including prevention of structural joint damage) in patients who have had an inadequate response to conventional therapies. In April 2021, Gilead Sciences K.K. applied for an additional indication of filgotinib as a treatment for patients with moderate to severe active ulcerative colitis.

Eisai will leverage its strong business foundation throughout Asia, provide new treatment options for patients with rheumatoid arthritis and inflammatory bowel disease, and contribute further to addressing the diverse needs of, and increasing the benefits provided to, patients their families, and healthcare providers.

1. About filgotinib

Filgotinib is a once-daily, oral, JAK1 preferential inhibitor. In Japan, filgotinib has been approved for the treatment of RA (including prevention of structural joint damage) in patients who have had an inadequate response to conventional therapies. In April 2021, Gilead Sciences K.K. applied for an additional indication of filgotinib as a treatment for patients with moderate to severe active ulcerative colitis.

In addition, filgotinib has been approved in the European Union and Great Britain for the treatment of adults with moderate to severe active rheumatoid arthritis who have responded inadequately or are intolerant to one or more disease modifying anti-rheumatic drugs (DMARDs). Filgotinib has also been approved in the European Union for the treatment of adult patients with moderately to severely active ulcerative colitis who have had an inadequate response with, lost response to, or were intolerant to either conventional therapy or a biologic agent. Applications have been submitted to the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) for the treatment of adults with moderately to severely active ulcerative colitis and are currently under review.

2. About the market for biological products South Korea, Taiwan, Hong Kong and Singapore

The market of biological products in 2020 in South Korea, Taiwan, Hong Kong and Singapore is approximately US $ 400 million, accounting for approximately more than 80% of the total market for biological products in Asia (Hong Kong, India, Indonesia, South Korea, Malaysia, Philippines, Singapore, Taiwan, Thailand and Vietnam).1 Many of biological products are adapted in the treatments for rheumatoid arthritis and inflammatory bowel disease.

First Patient Dosed in Australia in ATG-101 First-in-Human Trial

On December 19, 2021 Antengene Corporation Limited ("Antengene", SEHK: 6996.HK), a leading innovative global biopharmaceutical company dedicated to discovering, developing and commercializing first-in-class and/or best-in-class therapeutics in hematology and oncology, reported dosing in Australia of the first subject in the Phase I PROBE Trial, a first-in-human study of ATG-101 in patients with metastatic/advanced solid tumors and B-cell non-Hodgkin’s lymphoma (B-NHL) (Press release, Antengene, DEC 19, 2021, View Source [SID1234597415]). The primary objective of the study is to evaluate the safety and tolerability of ATG-101 and to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of ATG-101; the secondary objective is to evaluate preliminary anti-tumor activity of ATG-101.

ATG-101 is a novel bispecific antibody that was designed to block the binding of immunosuppressive PD-1/PD-L1 and conditionally induce 4-1BB stimulation, thus activating anti-tumor immune effectors, while delivering enhanced anti-tumor activity, with an improved safety profile. ATG-101 demonstrated significant anti-tumor activity in animal models of resistant tumors as well as those that progressed on anti-PD-1/L1 treatment. Furthermore, no liver toxicity was observed in GLP toxicology studies in cynomolgus monkeys with doses up to 100 mg/kg.

"ATG-101 has been specifically designed to combine the proven activity of PD-1 inhibition with the immune stimulating activity of 4-1BB. Our intent is to further enhance the role of immune-oncological drugs, by turning "cold" tumors "hot" and thereby improve outcomes for patients who do not respond to anti-PD-1/PD-L1 monotherapies, or regain control of disease that has become resistant or refractory to these drugs. This has become a growing and increasingly important medical need." said Dr. Kevin Lynch, Chief Medical Officer of Antengene. "PROBE is Antengene’s first global trial of an in-house developed, novel drug. The program is now enrolling patients in Australia, thereafter expanding to the U.S. where the IND has been cleared by the FDA. Dosing of the first subject is an important milestone, highlighting our cross-regional Discovery and Clinical execution capabilities. We are very grateful to the patients, investigators and study site staff for their dedication and support for this program and hope we will be able to make an important difference in cancer with ATG-101."

"As many patients with malignancies are resistant or refractory to current therapies, including chemotherapy, targeted therapy and monoclonal antibodies, there remains a need for novel treatments for this patient population," said Dr. Charlotte Lemech, Medical Director of Scientia Clinical Research in Sydney, Australia.

Dr. Lemech continued, "Accumulating evidence suggests that bispecific antibodies will fill an important role as one of these novel strategies. We are excited to be leading this clinical trial, the first to administer ATG-101 – a novel PD-L1/4-1BB bispecific antibody – bringing together a group of highly experienced Australian investigators to collaborate with Antengene. The design of ATG-101 incorporates a high affinity for PD-L1 and conditional activation of 4-1BB, which potentially reduces the risk of 4-1BB related liver toxicity. We are looking forward to assessing whether this bispecific antibody can provide enhanced efficacy with a better safety profile and a new option for these patients."

About the PROBE Trial
The PROBE trial is a first-in-human Phase I trial of ATG-101 in patients with metastatic/advanced solid tumors and mature B-cell non-Hodgkin lymphomas (B-NHL). The study will be conducted in the Dose Escalation Phase and Dose Expansion Phase, with the primary objective to evaluate the safety and tolerability of ATG-101 and to determine the MTD) and/or RP2D) of ATG-101, and the secondary objective to evaluate preliminary anti-tumor activity of ATG-101. The study will also evaluate a range of pharmacology, immunology and biomarker measurements.

About ATG-101
ATG-101 is a novel PD-L1/4-1BB bi-specific antibody being developed for the treatment of multiple kinds of cancer. ATG-101 was designed to activate anti-tumor immune effectors, by forming a cell-antibody-cell trimer to simultaneously block the binding of PD-L1/PD-1 and induce 4-1BB stimulation, with limited hepatoxicity. ATG-101 activates exhausted cells in vitro, signaling a potential in reversing T-cell dysfunction and exhaustion (on PD-1 cross-linking). In PD-L1 over-expressing cancer cells, ATG-101 demonstrated significant anti-tumor activity in animal tumors that progressed on anti-PD-1/L1 treatment and a favorable safety profile in GLP toxicology studies. Data from these studies, as well as unique computational semi-mechanistic pharmacology modeling work, was recently presented at the Society of Immunology and Cancer (SITC 2021).

Erasca Announces FDA Clearance of IND Application for ERAS-801 in Glioblastoma Multiforme and Collaboration with GCAR for Potential Inclusion in GBM AGILE Clinical Trial

On December 17, 2021 Erasca, Inc. (Nasdaq: ERAS), a clinical-stage precision oncology company singularly focused on discovering, developing, and commercializing therapies for patients with RAS/MAPK pathway-driven cancers, reported the United States Food and Drug Administration (FDA) has cleared an investigational new drug (IND) application for ERAS-801, an orally available small molecule epidermal growth factor receptor (EGFR) inhibitor specifically designed to have high central nervous system (CNS) penetration for the treatment of recurrent glioblastoma multiforme (rGBM) (Press release, Erasca, DEC 17, 2021, View Source [SID1234639381]). The company has also entered into a collaboration with the Global Coalition for Adaptive Research (GCAR) to determine the feasibility of the evaluation of ERAS-801 as part of the Glioblastoma Adaptive Global Innovative Learning Environment (GBM AGILE) trial.

"We are pleased with the pace at which our ERAS-801 program is advancing. Filing this IND a quarter ahead of schedule and receiving FDA clearance allows us to begin potentially helping patients sooner," said Jonathan E. Lim, M.D., Erasca’s chairman, CEO, and co-founder. "GBM is a rapid and aggressive malignancy for which patients have limited treatment options and a median overall survival of 17 months after diagnosis. Aberrant EGFR signaling is implicated in approximately 125,000 patients with GBM worldwide annually. ERAS-801’s profile of strong CNS penetrance and broad activity against EGFR amplifications driven by both oncogenic EGFR variants and wildtype EGFR has the potential to address significant unmet need in this patient population. We look forward to initiating our THUNDERBBOLT-1 Phase 1 trial evaluating ERAS-801 in patients with recurrent GBM in the first quarter of 2022."

Dr. Lim continued, "We are honored to enter into an early collaboration with GCAR, a leading nonprofit sponsoring the innovative GBM AGILE trial, which uses a streamlined, patient-centric approach to identify and advance the most effective treatment options for GBM more rapidly. GBM AGILE, an adaptive clinical trial that evaluates multiple drugs against a common comparator, is a seamless, international Phase 2/3 trial that we believe supports a clear registrational path in the United States and other key markets. Our early involvement with GCAR and the GBM Knowledge Network made up of industry leaders further reinforces the therapeutic promise of ERAS-801. We look forward to working together with GCAR and the GBM AGILE team to explore the robust potential of ERAS-801 in patients with GBM who are in much need of better treatment options."

ERAS-801 was designed and developed by a renowned team of cancer researchers—David Nathanson, Ph.D., Michael Jung, Ph.D., and Timothy Cloughesy, M.D. ERAS-801 was licensed from Katmai Pharmaceuticals, Inc.

About GBM AGILE
GBM AGILE is an international, innovative, long-standing platform trial designed to identify and advance effective therapies more rapidly through response adaptive randomization, data connectivity, and a seamless Phase 2/3 design. Conducted under a master protocol, the trial design allows simultaneous evaluation of multiple candidates as monotherapy or in combination against common controls. The operational infrastructure enables a more efficient and expedited approach to testing new therapies for GBM with the intent of lowering the cost, time, and number of patients required to evaluate potentially effective therapies. Data from the GBM AGILE trial has the potential to be used as the foundation for a new drug application (NDA) with the FDA and/or any comparable submission with other health authorities.

About ERAS-801
ERAS-801 is a highly potent, selective, reversible, and orally available small molecule EGFR inhibitor with significantly enhanced CNS penetration. In animal models, ERAS-801 had a 3.7:1 brain-to-plasma ratio and a Kp,uu (partition coefficient that measures unbound drug concentration) that was up to four times higher than approved EGFR inhibitors, indicating a higher concentration of unbound drug in the brain compared to the blood. At clinically relevant exposures, ERAS-801 demonstrated a survival benefit in nine out of 10 (90%) EGFR amplified glioblastoma patient-derived models tested and had statistically significantly higher brain penetrance and prolonged survival compared to approved EGFR tyrosine kinase inhibitors.

About THUNDERBBOLT-1
THUNDERBBOLT-1 will evaluate the safety, tolerability, and preliminary efficacy of ERAS-801 as a monotherapy in patients with recurrent GBM. The dose escalation portion will determine the recommended dose, which will then be used during the dose expansion portion to further evaluate the efficacy and safety of ERAS-801. Future sub-studies of THUNDERBBOLT-1 will potentially explore ERAS-801 in combination with other agents and in broader patient types. Dosing of the first patient in THUNDERBBOLT-1 is anticipated in the first quarter of 2022.

Bao Pharmaceutical and Medicilon reached a strategic collaboration

On December 17, 2021 Shanghai Bao Pharmaceutical Co., Ltd. (Bao) and Shanghai Medicilon Inc. (Medicilon) reported that it signed an innovative drug IND R&D service strategy collaboration agreement (Press release, Shanghai Medicilon, DEC 17, 2021, View Source [SID1234597766]).

Yanjun Liu, Chairman of Bao Pharmaceuticals; Zheng Wang, General Manager of Bao Pharmaceuticals; Chunlin Chen, Founder & CEO of Medicilon and Jinna Cai, Chief Commercial Officer of Medicilon, attended the signing ceremony to witness the collaboration event.

At the signing ceremony, Mengxian Yu, Deputy Secretary of the Party Committee and Mayor of Luodian Town, Baoshan District, delivered a speech, expressing sincere congratulations on the cooperation between the two parties and expressing the government’s high hopes and wishes for the project, "Bao Pharmaceutical is the first batch of companies to settle in the North Shanghai Biopharmaceuticals Industrial Park, and has a clear leading advantage in the differentiated competition of biopharmaceuticals. Medicilon is a leading professional biopharmaceuticals service company. For this collaboration, the government of Baoshan will give full support in terms of policy and environment. It is hoped that the collaboration between the two parties will be smooth and fruitful at an early stage to promote the higher-quality development of the North Shanghai Biopharmaceuticals Industrial Park."

Dr. Chunlin Chen, Founder & CEO of Medicilon, delivered a speech, thanking the government for supporting and witnessing this collaboration. In addition, Dr. Chen briefly introduced the development of Medicilon, and emphasized that Medicilon will gather a team of experts to promote the implementation of the project with high quality and efficiency. It is also hoped that in the long-term strategic collaboration between the two parties, many new drug R&D projects of Bao Pharmaceutical will be promoted to the clinic as soon as possible.

Yanjun Liu, Chairman of Bao Pharmaceuticals, said in his speech, "Medicilon is a professional and influential CRO, and Bao Pharmaceuticals is a specialty pharmaceutical company focusing on recombinant protein drugs and antibody drugs. The two parties will rely on Baoshan Luodian, a place that is favorable in time, place, and people, and complement each other’s strengths."

Bao Pharmaceutical and Medicilon reached a strategic collaboration
The two parties conducted in-depth exchanges and discussions on future collaboration, and formally signed a strategic collaboration agreement. At the same time, Medicilon awarded Bao Pharmaceuticals the title of "Innovative Drug IND R&D Service Strategic Partner". We are convinced that the in-depth collaboration between the two innovative companies will not only promote the research and development of recombinant protein drugs and antibody drugs in China, but will also have a profound impact on global new drug research and development.

In the future, Medicilon will continue to be an unswerving new drug enabler, helping global innovation partners to accelerate the development of new drugs, and forge ahead for the unfinished business of human health.

Entry into a Material Definitive Agreement

On December 17, 2021, Karyopharm Therapeutics Inc. (the "Company") reported that it entered into a License Agreement (the "Agreement") with Berlin-Chemie AG, an affiliate of the Menarini Group ("Menarini"), pursuant to which the Company granted Menarini a non-exclusive license to develop, and an exclusive license to commercialize, products containing selinexor, the Company’s lead Selective Inhibitor of Nuclear Export ("SINE") compound (the "Product"), for all human oncology indications in the European Economic Area, United Kingdom, Switzerland, Armenia, Azerbaijan, Belarus, Kazakhstan, Kyrgyzstan, Moldova, Russia, Tajikistan, Turkmenistan, Uzbekistan, Ukraine, Turkey, Mexico, all Central America countries and all South America countries (collectively, the "Territory") (Filing, 8-K, Karyopharm, DEC 17, 2021, View Source [SID1234597532]). In addition, the Company granted to Menarini a non-exclusive license to package and label the Product in or outside of the Territory for all human oncology indications solely to enable Menarini to commercialize the Product within the Territory.

Under the terms of the Agreement, the Company will use commercially reasonable efforts to develop the Product, transfer any marketing approval or authorization with respect to the Product in the Territory to Menarini and to complete any post-marketing approval or authorization studies required by a regulatory authority as a condition of maintaining the approval in any country in the Territory (the "Post-Registration Studies"). Menarini is obligated to use commercially reasonable efforts to apply for and obtain marketing approval or authorization of the Product, and to obtain price or reimbursement approval for the Product after approval of the relevant marketing approval or authorization, in each country of the Territory in each indication for which the Company has conducted a registrational clinical trial. Menarini is also obligated to use commercially reasonable efforts at its sole cost and expense to launch and commercialize the Product in each country of the Territory in each indication for which the Company has conducted a registrational clinical trial.

The Company will receive an upfront cash payment of $75.0 million in 2021, which we believe will extend the Company’s cash runway to early 2024. The Company is also entitled to receive up to $202.5 million in milestone payments from Menarini if certain development and sales performance milestones are achieved. The Company is further eligible to receive tiered royalties ranging from the mid-teens to mid-twenties based on future net sales of the Product in the Territory. The payments owed by Menarini to the Company are subject to reduction in specified circumstances. Menarini will reimburse the Company for 25% of all documented expenses incurred by the Company for the global development of the Product during 2022 through 2025, provided that such reimbursements shall not exceed $15.0 million per calendar year.

Menarini will purchase Product from the Company in accordance with a supply agreement to be entered into by the Company and Menarini (the "Supply Agreement"). The Company will supply all required quantities of selinexor and Product for the Territory as set forth in the Supply Agreement.

The development and commercialization of the Product for all human oncology indications in the Territory as contemplated by the Agreement will be subject to oversight by a joint steering committee composed of employees of the Company and Menarini, with the Company having final decision-making authority with regard to the development of the Product, as well as certain other technical, scientific and clinical operations matters, and Menarini having final decision-making authority with regard to the commercialization of the Product. Each party has also agreed to indemnify the other party from certain liabilities specified in the Agreement.

The Agreement will continue in effect on a country-by-country basis until the last to occur among: (i) the fifteenth anniversary of the first commercial sale of the Product in the applicable country, (ii) the expiration of the last-to-expire of the licensed patent rights in the applicable country or (iii) the expiration of any regulatory exclusivity protection covering the Product in such country. However, the Agreement may be terminated earlier by either party for (i) an uncured material breach of the Agreement by the other party (A) on a country-by-country basis with respect to the country to which the breach

relates if the breach is specific to such country and does not affect the Agreement as a whole or (B) in its entirety if the breach affects the Agreement as a whole, or (ii) in the event of the insolvency or bankruptcy of the other party. The Company may terminate the Agreement for certain patent challenges by Menarini.

The Company expects to file the Agreement as an exhibit to its Annual Report on Form 10-K for the year ended December 31, 2021. The foregoing is a description of certain terms

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EISAI ENTERS INTO COMMERCIALIZATION AND DISTRIBUTION AGREEMENT WITH GILEAD FOR JAK INHIBITOR FILGOTINIB IN ASIA

First Patient Dosed in Australia in ATG-101 First-in-Human Trial

Erasca Announces FDA Clearance of IND Application for ERAS-801 in Glioblastoma Multiforme and Collaboration with GCAR for Potential Inclusion in GBM AGILE Clinical Trial

Bao Pharmaceutical and Medicilon reached a strategic collaboration

Entry into a Material Definitive Agreement