On April 26, 2021 Evotec SE (Frankfurt Stock Exchange: EVT, MDAX/TecDAX, ISIN: DE0005664809) reported that Bristol Myers Squibb has decided to exercise their option to extend its partnership with Evotec in the field of targeted protein degradation (Press release, Evotec, APR 26, 2021, View Source;announcements/press-releases/p/bristol-myers-squibb-exercises-option-to-extend-targeted-protein-degradation-partnership-with-evotec-6057 [SID1234578444]). Evotec and Bristol Myers Squibb (the successor in interest to Celgene) initiated this strategic drug discovery and development partnership in 2018 with the goal to identify first-in-class drug candidates initially focusing on solid tumours.

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The partnership leverages Evotec’s proprietary PanOmics platform, which combines enhanced throughput proteomics, high throughput transcriptomics and cell imaging with the integrated data analysis platform PanHunter. Together with Evotec’s deep insights into the disease biology of oncology, the approach has generated a pipeline of novel first-in-class targeted protein degradation projects, two of which have transitioned successfully into lead optimisation after completing respective validation processes on Evotec’s platforms.

The high quality of the data and the number of promising drug targets identified using Evotec’s PanOmics and PanHunter platforms has led to the early extension of the partnership. The extension triggers an undisclosed payment to Evotec to further expand screening efforts and thus continue to grow the pipeline.

Dr Cord Dohrmann, Chief Scientific Officer of Evotec, said: "Targeted protein degradation is an emerging new therapeutic modality with enormous potential to reach not only proven drug targets through a novel mechanism of action, but also traditionally undruggable targets and thus discover and develop first-in-class, disease-modifying therapeutics. The success of our collaboration with Bristol Myers Squibb to date has led to Bristol Myers Squibb’s decision to expand and extend this collaboration. We are honoured and extremely proud to collaborate with the industry-leading company in the field of protein homeostasis and are very much looking forward to continue our efforts at an accelerated pace."

On April 26, 2021 AstraZeneca and MSD reported that its selumetinib has been recommended for conditional marketing authorisation in the European Union (EU) for the treatment of symptomatic, inoperable plexiform neurofibromas (PN) in paediatric patients with neurofibromatosis type 1 (NF1) aged three years and above (Press release, AstraZeneca, APR 26, 2021, View Source [SID1234578442]).1

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NF1 is a debilitating genetic condition affecting 1 in 3,000 individuals worldwide.2,3 In 30-50% of people with NF1, tumours develop on the nerve sheaths (plexiform neurofibromas) and can cause clinical issues such as disfigurement, motor dysfunction, pain, airway dysfunction, visual impairment, and bladder/bowel dysfunction.4,5-8

The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency based its positive opinion on results from the National Cancer Institute (NCI) Cancer Therapy Evaluation Program (CTEP)-sponsored SPRINT Stratum 1 Phase II trial. Results were published in The New England Journal of Medicine.8 Safety and efficacy data from the SPRINT trial with longer follow up will be provided to the CHMP as a condition of the recommendation for approval.

The trial showed selumetinib demonstrated an objective response rate (ORR) of 66% (33 of 50 patients, confirmed partial response) in paediatric patients with NF1 PN when treated with selumetinib as twice-daily oral monotherapy.1 ORR is defined as the percentage of patients with confirmed complete or partial response of at least 20% reduction in tumour volume.1

Dave Fredrickson, Executive Vice President, Oncology Business Unit, said: "This recommendation means patients in the EU are one step closer to receiving the only approved medicine for neurofibromatosis type 1 and the only treatment outside of surgery, which is not an option for many patients. Children living with this rare genetic condition are in great need of novel treatment options to help address the impact of this disease."

Roy Baynes, Senior Vice President and Head of Global Clinical Development, Chief Medical Officer, MSD Research Laboratories, said: "In the SPRINT trial, selumetinib was shown to reduce the size of these inoperable tumours, a meaningful clinical advance for children living with this debilitating disease. We are pleased to be one step closer to bringing this important treatment option to these paediatric patients in the EU."

Selumetinib was approved in the US in April 2020 for the treatment of paediatric patients with NF1 and symptomatic, inoperable PN under the medicine name Koselugo.7 Further regulatory submissions are underway. Clinical trials of selumetinib in adult patients with NF1 PN, and in an alternative age-appropriate formulation for paediatric patients, are scheduled to begin this year.

NF1
NF1 is caused by a spontaneous or inherited mutation in the NF1 gene and is associated with many symptoms, including soft lumps on and under the skin (cutaneous neurofibromas) and skin pigmentation (so-called ‘café au lait’ spots). In 30-50% of people, tumours develop on the nerve sheaths.2,4,9,10 These PN can cause clinical issues such as pain, motor dysfunction, airway dysfunction, bladder/bowel dysfunction and disfigurement as well as having the potential to transform into malignant peripheral nerve sheath tumours.5-8 PN begin developing during early childhood, with varying degrees of severity, and can reduce life expectancy by eight to 15 years.6,12

SPRINT
The SPRINT Stratum 1 Phase I/II trial was designed to evaluate the objective response rate and impact on patient-reported and functional outcomes in paediatric patients with NF1-related inoperable PNs treated with selumetinib monotherapy.11 This trial sponsored by NCI CTEP was conducted under a Cooperative Research and Development Agreement between NCI and AstraZeneca with additional support from Neurofibromatosis Therapeutic Acceleration Program (NTAP).

Selumetinib
Selumetinib is an inhibitor of mitogen-activated protein kinase kinases 1 and 2 (MEK1/2).1 MEK1/2 proteins are upstream regulators of the extracellular signal-related kinase (ERK) pathway. Both MEK and ERK are critical components of the RAS-regulated RAF-MEK-ERK pathway, which is often activated in different types of cancers.11

Selumetinib received US FDA Breakthrough Therapy Designation in April 2019, Rare Pediatric Disease Designation in December 2019 and US Orphan Drug Designation in February 2018. Further orphan drug designations have been granted in the EU, Japan, Russia, Switzerland, South Korea, Taiwan and Australia.

AstraZeneca and MSD strategic oncology collaboration
In July 2017, AstraZeneca and Merck & Co., Inc., Kenilworth, NJ, US, known as MSD outside the US and Canada, announced a global strategic oncology collaboration to co-develop and co-commercialise Lynparza, the world’s first PARP inhibitor, and Koselugo (selumetinib), a MEK inhibitor, for multiple cancer types. Working together, the companies will develop Lynparza and Koselugo in combination with other potential new medicines and as monotherapies. Independently, the companies will develop Lynparza and Koselugo in combination with their respective PD-L1 and PD-1 medicines.

AstraZeneca in oncology
AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients.

The Company’s focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyse changes in the practice of medicine and transform the patient experience.

AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death.

On April 26, 2021 AstraZeneca reported that its Tagrisso (osimertinib) has been recommended for marketing authorisation in the European Union for the adjuvant treatment of adult patients with early-stage (IB, II and IIIA) epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC) after complete tumour resection with curative intent (Press release, AstraZeneca, APR 26, 2021, View Source [SID1234578441]). If approved, Tagrisso will be indicated for EGFRm patients whose tumours have exon 19 deletions or exon 21 (L858R) mutations.

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The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency based its positive opinion on results from the ADAURA Phase III trial. In the trial, Tagrisso demonstrated a statistically significant and clinically meaningful improvement in disease-free survival (DFS) in the primary analysis population of patients with Stage II and IIIA EGFRm NSCLC, and in the overall trial population of patients with Stage IB-IIIA disease. These results were published in The New England Journal of Medicine.

While up to 30% of all patients with NSCLC may be diagnosed early enough to have surgery with curative intent, recurrence is still common in early-stage disease. Historically, nearly half of patients diagnosed in Stage IB, and over three quarters of patients diagnosed in Stage IIIA, have experienced recurrence within five years.1-3

Dave Fredrickson, Executive Vice President, Oncology Business Unit, said: "With no targeted treatment options currently available for early-stage lung cancer patients after surgery in the EU, recurrence rates remain unacceptably high. This positive recommendation is a vital step towards introducing a targeted treatment option for these patients for the first time. It also reinforces the urgency to test all lung cancer patients for tumour mutations before making any treatment decisions to ensure that as many patients as possible can benefit from innovative therapies, like Tagrisso, when they become available."

Tagrisso is approved to treat early-stage lung cancer in more than fifteen countries, including the US and China, and additional global regulatory reviews are ongoing. Tagrisso is also approved for the 1st-line treatment of patients with locally advanced or metastatic EGFRm NSCLC and for the treatment of locally advanced or metastatic EGFR T790M mutation-positive NSCLC in the EU, the US, Japan, China and many other countries.

Lung cancer
Lung cancer is the leading cause of cancer death among both men and women, accounting for about one-fifth of all cancer deaths.4 Lung cancer is broadly split into NSCLC and small cell lung cancer, with 80-85% classified as NSCLC.5 The majority of NSCLC patients are diagnosed with advanced disease while approximately 25-30% present with resectable disease at diagnosis.1-2 Early-stage lung cancer diagnoses are often only made when the cancer is found on imaging for an unrelated condition.6-7

For patients with resectable tumours, the majority of patients eventually develop recurrence despite complete tumour resection and adjuvant chemotherapy.3

Approximately 10-15% of NSCLC patients in the US and Europe, and 30-40% of patients in Asia have EGFRm NSCLC.8-10 These patients are particularly sensitive to treatment with an EGFR-tyrosine kinase inhibitor (TKI) which blocks the cell-signalling pathways that drive the growth of tumour cells.11

ADAURA
ADAURA is a randomised, double-blind, global, placebo-controlled Phase III trial in the adjuvant treatment of 682 patients with Stage IB, II and IIIA EGFRm NSCLC following complete tumour resection and adjuvant chemotherapy as indicated. Patients were treated with Tagrisso 80mg once-daily oral tablets or placebo for three years or until disease recurrence.

The trial enrolled patients in more than 200 centres across more than 20 countries, including the US, in Europe, South America, Asia and the Middle East. The primary endpoint was DFS in Stage II and IIIA patients and a key secondary endpoint was DFS in Stage IB, II and IIIA patients.

The data readout was originally anticipated in 2022. In April 2020, an Independent Data Monitoring Committee recommended for the trial to be unblinded two years early based on a determination of overwhelming efficacy. Investigators and patients continue to participate and remain blinded to treatment. The trial will continue to assess overall survival.

Tagrisso
Tagrisso (osimertinib) is a third-generation, irreversible EGFR-TKI with clinical activity against central nervous system metastases. Tagrisso (40mg and 80mg once-daily oral tablets) has been used to treat approximately 250,000 patients across indications worldwide and AstraZeneca continues to explore Tagrisso as a treatment for patients across multiple stages of EGFRm NSCLC.

In Phase III trials, Tagrisso is being tested in the Stage III locally advanced unresectable setting (LAURA), in the neoadjuvant resectable setting (NeoADAURA) and in combination with chemotherapy (FLAURA2). AstraZeneca is also researching ways to address tumour mechanisms of resistance through the SAVANNAH and ORCHARD Phase II trials, which test Tagrisso given concomitantly with savolitinib, an oral, potent and highly selective MET TKI, as well as other potential new medicines.

AstraZeneca in lung cancer
AstraZeneca has a comprehensive portfolio of approved and potential new medicines in late-stage development for the treatment of different forms of lung cancer spanning different histologies, stages of disease, lines of therapy and modes of action. These medicines include Tagrisso (osimertinib), Imfinzi (durvalumab), Enhertu (trastuzumab deruxtecan), datopotamab deruxtecan and savolitinib.

AstraZeneca in oncology
AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients.

The Company’s focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyse changes in the practice of medicine and transform the patient experience.

AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death.

On April 26, 2021 InnoCare Pharma reported The 2021 edition of the Chinese Society of Clinical Oncology (CSCO) Lymphoma Diagnosis and Treatment Guidelines (hereinafter referred to as the "Guidelines") was released recently (Press release, InnoCare Pharma, APR 26, 2021, View Source [SID1234578432]). InnoCare’s novel BTK inhibitor orelabrutinib was listed as a Level I recommended treatment for relapsed or refractory (r/r) chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) and r/r mantle cell lymphoma (MCL).

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In addition, for r/r diffuse large B-cell lymphoma (DLBCL), the Guidelines recommend that BTK inhibitors be considered to be used in combination with chemotherapy, and specifically mentioned that innovative drugs such as orelabrutinib be recommended for single or combinational therapy for r/r DLBCL based on preliminary efficacy in clinical studies. For primary central nervous system lymphoma (PCNSL), BTK inhibitor orelabrutinib demonstrates good blood-brain barrier penetration. The Guidelines recommend BTK inhibitors to be used in combination with chemotherapy, and specifically pointed out that orelabrutinib is expected to show efficacy in the treatment of PCNSL.

The Guidelines are aimed at further promoting the standardization of lymphoma diagnosis and treatment in China.

Professor Jun Ma, Chairman of the CSCO Board of Supervision and Director of the Harbin Institute of Hematology, said: "Lymphoma is one of the top ten most common tumors in China, and it is also the fastest growing hematological malignant tumor in recent years. The five-year survival rate of lymphoma patients in China still lags behind that of U.S. and Europe. Therefore, it is very important to standardize the diagnosis and treatment. The CSCO Guidelines not only reflect the continuous improvement of drug research and development in China, but also contribute to the standardization of lymphoma diagnosis and treatment, which will benefit patients."

Professor Jun Zhu, Executive Director of the CSCO, Director of the Lymphoma Department of Peking University Cancer Hospital, said: "As the principal investigator of orelabrutinib, I am very pleased that orelabrutinib has been recognized by the experts and recommended by the Guidelines. As a lymphoma physician, we can provide Chinese patients with better anti-tumor drugs, so that our patients can obtain greater benefit. This is what we have been striving for."

"Orelabrutinib was recommended by the CSCO Guidelines four months after its approval, which demonstrates the recognition for orelabrutinib by CSCO experts. With the further improvement of research and development, we believe that our lymphoma diagnosis and treatment can be further refined and standardized to better benefit patients in China." said Dr. Jasmine Cui, co-founder, chairwoman and CEO of InnoCare.

Orelabrutinib is a novel BTK inhibitor with high target selectivity. It was approved for marketing by the National Medical Products Administration (NMPA) of China on December 25, 2020 for the treatment of patients with r/r CLL/SLL and r/r MCL.

On April 25, 2021 Samsung Biologics (KRX: 207940.KS), the world’s leading contract development and manufacturing organization and TG Therapeutics (NASDAQ: TGTX), reported an expansion of a large-scale contract manufacturing deal for the supply of TG Therapeutics’ ublituximab, an investigational anti-CD20 monoclonal antibody (Press release, Samsung BioLogics, APR 25, 2021, View Source [SID1234578437]). TG Therapeutics has completed a rolling submission of a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) requesting approval of ublituximab, in combination with UKONIQ (umbralisib), TG Therapeutics’ oral once-daily inhibitor of PI3K-delta and CK1-epsilon, as a treatment for patients with CLL, based primarily on the positive results from the UNITY-CLL Phase 3 trial. Ublituximab was also the subject of two successful Phase 3 trials in patients with relapsing forms of multiple sclerosis (RMS) and a BLA is currently being prepared for this indication.

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Samsung Biologics and TG Therapeutics Expand Collaboration for the Large Scale Manufacture of Ublituximab
"We are very glad to be able to flexibly accommodate our client’s expanded needs through our facilities," John Rim, CEO of Samsung Biologics, commented. Rim added, "By supporting TG Therapeutics in this partnership, we are contributing to bringing needed treatments to patients around the world and getting a step closer to our vision of bringing about a better life for humanity."

Michael S. Weiss, Executive Chairman and CEO of TG Therapeutics, stated, "Samsung is the global leader in biologics manufacturing and we are happy to have them as our partner as we look forward to the potential commercialization of ublituximab across both oncology and autoimmune indications. With the recent positive ULTIMATE I and II MS Phase 3 studies, we re-evaluated our supply needs and were very pleased we were able to secure the long-term capacity we believe we will need to meet the potential global demand for ublituximab. This is an important next step in our long-standing relationship with Samsung."

In order to support all its current and potential clients around the world, Samsung Biologics is currently building its fourth and largest biomanufacturing facility in Incheon, Korea. Upon completion of the said plant in 2023, Samsung Biologics will hold 620,000 liters of biomanufacturing capacity, or approximately a quarter of the entire bio-CMO capacity globally. The company provides contract manufacturing, contract development, and testing services all from a single location, offering end-to-end services for its clients.

ABOUT UBLITUXIMAB
Ublituximab is an investigational glycoengineered monoclonal antibody that targets a unique epitope on CD20-expressing B-cells. When ublituximab binds to the B-cell it triggers a series of immunological reactions, including antibody-dependent cellular cytotoxicity (ADCC) and complement dependent cytotoxicity (CDC), leading to destruction of the cell. Additionally, ublituximab is uniquely designed, to lack certain sugar molecules normally expressed on the antibody. Removal of these sugar molecules, a process called glycoengineering, has been shown to enhance the potency of ublituximab, especially the ADCC activity. Targeting CD20 using monoclonal antibodies has proven to be an important therapeutic approach for the management of B-cell malignancies and autoimmune disorders, both diseases driven by the abnormal growth or function of B-cells.