On June 18, 2020 Ascentage Pharma (6855.HK), a globally focused, clinical-stage biotechnology company engaged in developing novel therapies for cancers, chronic hepatitis B (CHB), and age-related diseases, reported that Guangzhou Healthquest Pharma Co., Ltd, a wholly-owned subsidiary of Ascentage Pharma’s, has submitted a New Drug Application (NDA) to the Center for Drug Evaluation (CDE) of China National Medical Products Administration (NMPA) for HQP1351 for the treatment of patients with T315I-mutant chronic phase chronic myeloid leukemia (CP-CML) and accelerated phase CML (AP-CML) (Press release, Ascentage Pharma, JUN 18, 2020, View Source [SID1234561220]). This is Ascentage Pharma’s first NDA submission since its inception. If approved, HQP1351 will become the first third-generation BCR-ABL inhibitor therapeutics in China.

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Ascentage Pharma recently engaged in pre-NDA discussions with the CDE regarding the NDA based on results from two pivotal studies in patients with T315I-mutant CP-AML and AP-CML. The CDE has agreed that the company should proceed to submit the NDA for those two indications.

CML is a hematologic malignancy of the white blood cells. BCR-ABL tyrosine kinase inhibitors (TKI) have significantly improved the clinical management of CML. However, despite clinical benefits offered by the first-generation BCR-ABL inhibitor imatinib (GLEEVEC), and several second-generation TKIs, acquired resistance to TKIs remains a major challenge in the treatment of CML. BCR-ABL tyrosine kinase mutations represent a key mechanism of acquired drug resistance; T315I, which is the most common drug-resistant mutation, occurs in about 25% of patients with drug-resistant CML. Patients with T315I-mutant CML are resistant to both first- and second-generation BCR-ABL inhibitors, hence presenting an urgent unmet medical need for effective treatment.

HQP1351 is a novel, orally active, potent third-generation BCR-ABL inhibitor designed to effectively target BCR-ABL mutants, including T315I, and the first China-developed third-generation BCR-ABL inhibitor targeting drug-resistant CML. In July 2019, HQP1351 was cleared by the US Food and Drug Administration (FDA) to enter a Phase Ib clinical study. In May 2020, HQP1351 was granted an Orphan Drug Designation and a Fast Track Designation by the US FDA.

"As Ascentage Pharma’s first NDA and one that may lead to the market authorization of the first third-generation BCR-ABL inhibitor in China, this submission marks a major milestone for our company," said Dr. Dajun Yang, Chairman & CEO of Ascentage Pharma. "For patients with CML who cannot be effectively treated by currently available TKIs, there remains an urgent unmet medical need for safer and more effective therapies. We hope that HQP1351 will bring a breakthrough to the current conundrum and benefit more patients."

On June 18, 2020 Linnaeus Therapeutics, Inc. (Linnaeus), a privately held clinical-stage biopharmaceutical company focused on the development and commercialization of novel small-molecule oncology therapeutics, reported that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation for LNS8801 for the treatment of patients with metastatic or unresectable melanoma who have progressed on or after anti–programmed cell death receptor or ligand (anti–PD-1/L1) therapy (Press release, Linnaeus Therapeutics, JUN 18, 2020, View Source [SID1234561237]).

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Linnaeus is currently evaluating LNS8801 in a phase 1 clinical trial in patients with advanced cancer. The company expects to identify the recommended phase 2 dose this summer and to begin its phase 2 program evaluating LNS8801 as a monotherapy and in combination with targeted therapies in early fall.

LNS8801 is a first-in-class, orally bioavailable, small-molecule that is a highly specific and potent agonist of the G-protein estrogen receptor (GPER). GPER is widely expressed on cancers. Agonizing GPER both stops cancers from proliferating and makes them more visible to the immune system.

"Receiving Fast Track designation for LNS8801 is an important step in its clinical development as we near the end of our phase 1 dose-escalation study and advance LNS8801 into phase 2 clinical trials," said Patrick Mooney, MD, Chief Executive Officer of Linnaeus. "We are pleased that the FDA recognizes the potential of LNS8801 to help patients with melanoma who have progressed after anti–PD-1/L1 therapy."

About Fast Track Designation
Fast Track designation is a process designed to facilitate the expedited development and review of new drugs that treat serious or life-threatening conditions and that have demonstrated the potential to fill an unmet medical need. The purpose is to advance new drugs earlier for patients who need them.

A company with a drug that receives Fast Track designation is eligible for some or all of the following:

More frequent meetings with the FDA to discuss the drug’s development and ensure collection of the appropriate data needed to support drug approval
More frequent written communication from the FDA about such things as the design of the proposed clinical trials and use of biomarkers
Eligibility for Accelerated Approval and Priority Review if relevant criteria are met
Rolling Review, which means that a drug company can submit completed sections of its New Drug Application (NDA) for review by the FDA, rather than waiting until every section of the NDA is completed before the entire application can be reviewed. NDA review usually does not begin until the drug company has submitted the entire application to the FDA.
About LNS8801
LNS8801 is an orally bioavailable and highly specific agonist of GPER whose activity is dependent on the expression of GPER. GPER activation suppresses well-known tumor-associated genes, such as c-Myc and PD-L1. In preclinical cancer models, LNS8801 displays potent antitumor activities across a wide range of tumor types, rapidly shrinking tumors and inducing immune memory. LNS8801 monotherapy has shown significant antitumor activity, including inducing complete responses that are immune to rechallenge. LNS8801 also has shown effects when combined with targeted therapies, chemotherapies, and immunotherapies. LNS8801 is currently in a phase 1/2 clinical trial in patients with advanced cancer at six comprehensive cancer centers in the United States.

On June 18, 2020 Bristol Myers Squibb reported a drug discovery collaboration with Ubiquigent that it inherited in its merger with Celgene (Press release, Bristol-Myers Squibb, JUN 18, 2020, View Source [SID1234561257]). The Big Pharma recently scrapped an alliance with Jounce Therapeutics that was formed by Celgene but is sticking with deubiquitinase (DUB) enzyme specialist Ubiquigent.

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Celgene’s business was built around some of the areas in which Ubiquigent specializes. Thalidomide, Pomalyst and Revlimid—key drugs in Celgene’s product portfolio—all act on E3 ubiquitin ligases, a group of proteins involved in protein degradation. Celgene also struck protein degradation deals with Evotec, Nurix and Vividion Therapeutics in the years leading up to its merger with Bristol Myers.

In exploring the area, Celgene also entered into a drug discovery collaboration with Ubiquigent, a Scottish biotech that seeks to drive protein degradation through molecules that act on the ubiquitin system. Ubiquigent’s capabilities have landed it deals with companies including Forma Therapeutics.

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Bristol Myers has less of a legacy in the field than Celgene does, but it appears to have decided to build on the experience it acquired in the takeover. Ubiquigent’s statement about the continuation of the deal it signed with Celgene follows comments by Bristol Myers about the potential to get at undruggable targets via the ubiquitin-proteasome system.

"We’ve realized we can degrade hundreds of previously unrecognized proteins, and this number is the tip of the iceberg. There is potentially the ability to target perhaps thousands of protein targets. We’ve just scratched the surface when it comes to understanding how many proteins we can target, and our job now is to figure out which have therapeutic utility," Bristol Myers Senior Vice President Mark Rolfe said in a statement.

Bristol Myers published the comments made by Rolfe, who joined the company in the Celgene deal, weeks before releasing a Q&A with Josh Hansen about protein homeostasis. Hansen, who like Rolfe worked at a West Coast site Bristol Myers acquired from Celgene, cited solid tumors and immune diseases as conditions potentially amenable to treatment through protein degradation.

On June 18, 2020 Linnaeus Therapeutics, Inc. (Linnaeus), a privately held clinical-stage biopharmaceutical company focused on the development and commercialization of novel small-molecule oncology therapeutics, reported that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation for LNS8801 for the treatment of patients with metastatic or unresectable melanoma who have progressed on or after anti–programmed cell death receptor or ligand (anti–PD-1/L1) therapy (Press release, Linnaeus Therapeutics, JUN 18, 2020, View Source [SID1234561305]).

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Linnaeus is currently evaluating LNS8801 in a phase 1 clinical trial in patients with advanced cancer. The company expects to identify the recommended phase 2 dose this summer and to begin its phase 2 program evaluating LNS8801 as a monotherapy and in combination with targeted therapies in early fall.

LNS8801 is a first-in-class, orally bioavailable, small-molecule that is a highly specific and potent agonist of the G-protein estrogen receptor (GPER). GPER is widely expressed on cancers. Agonizing GPER both stops cancers from proliferating and makes them more visible to the immune system.

"Receiving Fast Track designation for LNS8801 is an important step in its clinical development as we near the end of our phase 1 dose-escalation study and advance LNS8801 into phase 2 clinical trials," said Patrick Mooney, MD, Chief Executive Officer of Linnaeus. "We are pleased that the FDA recognizes the potential of LNS8801 to help patients with melanoma who have progressed after anti–PD-1/L1 therapy."

About Fast Track Designation

Fast Track designation is a process designed to facilitate the expedited development and review of new drugs that treat serious or life-threatening conditions and that have demonstrated the potential to fill an unmet medical need. The purpose is to advance new drugs earlier for patients who need them.

A company with a drug that receives Fast Track designation is eligible for some or all of the following:

More frequent meetings with the FDA to discuss the drug’s development and ensure collection of the appropriate data needed to support drug approval
More frequent written communication from the FDA about such things as the design of the proposed clinical trials and use of biomarkers
Eligibility for Accelerated Approval and Priority Review if relevant criteria are met
Rolling Review, which means that a drug company can submit completed sections of its New Drug Application (NDA) for review by the FDA, rather than waiting until every section of the NDA is completed before the entire application can be reviewed. NDA review usually does not begin until the drug company has submitted the entire application to the FDA.
About LNS8801

LNS8801 is an orally bioavailable and highly specific agonist of GPER whose activity is dependent on the expression of GPER. GPER activation suppresses well-known tumor-associated genes, such as c-Myc and PD-L1. In preclinical cancer models, LNS8801 displays potent antitumor activities across a wide range of tumor types, rapidly shrinking tumors and inducing immune memory. LNS8801 monotherapy has shown significant antitumor activity, including inducing complete responses that are immune to rechallenge. LNS8801 also has shown effects when combined with targeted therapies, chemotherapies, and immunotherapies. LNS8801 is currently in a phase 1/2 clinical trial in patients with advanced cancer at six comprehensive cancer centers in the United States.

On June 18, 2020 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported that the Phase III IMpassion031 study, evaluating Tecentriq (atezolizumab) in combination with chemotherapy (Abraxane, albumin-bound paclitaxel; nab-paclitaxel; followed by doxorubicin and cyclophosphamide) in comparison to placebo plus chemotherapy (including Abraxane), met its primary endpoint by demonstrating a statistically significant and clinically meaningful improvement in pathological complete response (pCR) for the treatment of people with early triple-negative breast cancer (TNBC), regardless of PD-L1 expression (Press release, Hoffmann-La Roche, JUN 18, 2020, View Source [SID1234561205]).

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"Triple-negative breast cancer remains an aggressive disease with high rates of recurrence," said Levi Garraway, M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global Product Development. "Our goal in treating TNBC at its earliest stages is to provide people with the best chance for a future cure. Adding Tecentriq to chemotherapy now has the potential to help women with TNBC at multiple different stages of the disease."

In the study, fewer patients who received the Tecentriq combination as a neoadjuvant (before surgery) treatment had evidence of tumour tissue detectable at the time of surgery (known as pCR), regardless of PD-L1 expression, in comparison to the control arm. Neoadjuvant treatment may allow a doctor to quickly assess whether a medicine is working and may also reduce a tumour’s size so it is easier to surgically remove. pCR is a common measure of neoadjuvant treatment effect and can be assessed more quickly than traditional endpoints in early stage breast cancer.

Safety for the Tecentriq combination appeared to be consistent with the known safety profiles of the individual medicines and no new safety signals were identified. Results of the IMpassion031 study will be presented at an upcoming medical meeting and will be discussed with global health authorities including the US Food and Drug Administration (FDA) and European Medicines Agency (EMA).

The IMpassion031 study is the second positive Phase III study from Roche demonstrating the benefit of Tecentriq in TNBC, and the first Tecentriq study to demonstrate benefit in early TNBC. Tecentriq in combination with nab-paclitaxel is currently approved in more than 70 countries worldwide, including the US and across Europe, for the treatment of adults with unresectable locally advanced or metastatic TNBC in people whose tumours express PD-L1 (IC≥1%).

Roche has an extensive development programme for Tecentriq, including multiple ongoing and planned Phase III studies across lung, genitourinary, skin, breast, gastrointestinal, gynaecological, and head and neck cancers. This includes studies evaluating Tecentriq both alone and in combination with other medicines.

About the IMpassion031 study
The IMpassion031 study is a Phase III, multicentre, randomised, double-blind study evaluating the efficacy and safety of Tecentriq in combination with chemotherapy (nab-paclitaxel; followed by doxorubicin and cyclophosphamide) in comparison to placebo plus chemotherapy, in people with previously untreated, early TNBC. The study enrolled 333 people who were randomised in a 1:1 ratio to receive Tecentriq or placebo plus chemotherapy in the neoadjuvant (before surgery) setting. Treatment with Tecentriq continued adjuvantly (after surgery) for those in the Tecentriq arm of the study. The primary endpoint is pCR using the American Joint Committee on Cancer (AJCC) staging system in the intention-to-treat (ITT) population and in the PD-L1-positive population. Secondary endpoints include overall survival (OS), event-free survival, disease-free survival and quality of life measures.

About triple-negative breast cancer
Breast cancer is the most common cancer among women with more than 2 million diagnosed worldwide each year.1 TNBC represents ~15% of all breast cancers and is more common in women under the age of 50, compared with other forms of breast cancer.2-4 It is defined by the lack of expression and/or amplification of the targetable receptors for oestrogen, progesterone and HER2 amplification.5 Patients with metastatic TNBC generally experience rapid progression and shorter OS compared to other subtypes of breast cancer.3

About Roche in breast cancer
Roche has been advancing breast cancer research for more than 30 years with the goal of helping as many people with the disease as possible. Our medicines, along with companion diagnostic tests, have contributed to bringing breakthrough innovations in HER2-positive and triple-negative breast cancers. As our understanding of breast cancer biology rapidly improves, we are working to identify new biomarkers and approaches to treatment for all forms of early and advanced breast cancer, including triple-negative and hormone receptor-positive.

Our targeted medicines Herceptin, Perjeta, Kadcyla and Tecentriq are continuing to transform the treatment of early and advanced HER2-postive and triple-negative breast cancers and, through our Tecentriq and ipatasertib clinical programmes, we hope to bring new treatment combinations to people with breast cancer, ultimately improving outcomes.

About Tecentriq
Tecentriq is a monoclonal antibody designed to bind with a protein called PD-L1, which is expressed on tumour cells and tumour-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, Tecentriq may enable the activation of T-cells. Tecentriq is a cancer immunotherapy that has the potential to be used as a foundational combination partner with other immunotherapies, targeted medicines and various chemotherapies across a broad range of cancers. The development of Tecentriq and its clinical programme is based on our greater understanding of how the immune system interacts with tumours and how harnessing a person’s immune system combats cancer more effectively.

Tecentriq is approved in the US, EU and countries around the world, either alone or in combination with targeted therapies and/or chemotherapies in various forms of non-small cell and small cell lung cancer, certain types of metastatic urothelial cancer and in PD-L1-positive metastatic triple-negative breast cancer. In the US, Tecentriq in combination with Avastin is approved for people with unresectable or metastatic hepatocellular carcinoma.

About Roche in cancer immunotherapy
Roche’s rigorous pursuit of groundbreaking science has contributed to major therapeutic and diagnostic advances in oncology over the last 50 years, and today, realising the full potential of cancer immunotherapy is a major area of focus. With over 20 molecules in development, Roche is investigating the potential benefits of immunotherapy alone, and in combination with chemotherapy, targeted therapies or other immunotherapies with the goal of providing each person with a treatment tailored to harness their own unique immune system to attack their cancer. Our scientific expertise, coupled with innovative pipeline and extensive partnerships, gives us the confidence to continue pursuing the vision of finding a cure for cancer by ensuring the right treatment for the right patient at the right time.

In addition to Roche’s approved PD-L1 checkpoint inhibitor, Tecentriq (atezolizumab), Roche’s broad cancer immunotherapy pipeline includes other checkpoint inhibitors, such as tiragolumab, a novel cancer immunotherapy designed to bind to TIGIT, individualised neoantigen therapies and T-cell bispecific antibodies. To learn more about Roche’s scientific-led approach to cancer immunotherapy, please follow this link:
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