On July 7, 2021 Takeda Pharmaceutical Company Limited (TSE: 4502/NYSE: TAK) ("Takeda") reported that the Center for Drug Evaluation (CDE) of the National Medical Products Administration of China (NMPA) has accepted the company’s New Drug Application (NDA) for mobocertinib (TAK-788) and granted priority review for this Class-1 innovative drug, for the treatment of adult patients with non-small cell lung cancer(NSCLC) with epidermal growth factor receptor (EGFR) Exon20 insertion mutations (Press release, Takeda, JUL 7, 2021, View Source [SID1234586735]). Mobocertinib is the first oral therapy specifically designed to target EGFR Exon20 insertion mutations. The U.S. Food and Drug Administration (FDA) recently granted priority review for the company’s New Drug Application for mobocertinib with a Prescription Drug User Fee Act (PDUFA) target action date set for October 26, 2021.

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"Patients with EGFR Exon20 insertion+ mNSCLC face critical unmet needs in China," said Sean Shan, president of Takeda in China. "The acceptance by CDE marks an important step to accelerate the delivery of innovative treatments to patients with limited therapeutic options. The Chinese government’s healthcare reforms are rewarding innovation which also present an opportunity for Takeda’s current portfolio and pipeline of innovative and life transforming medicines."

The EGFR Exon20 insertion mutation is a rare mutation in non-small cell lung cancer (NSCLC). In China, the incidence of NSCLC with the EGFR Exon20 insertion mutations accounts for about 2.3 percent of all NSCLC cases[1]. Currently, there are no approved therapies targeting EGFR Exon20 insertion mutations, and the current EGFR TKIs and chemotherapy provide limited benefits for these patients whose clinical needs are very urgent[2].

"Takeda is committed to bringing established innovative products as well as exciting, new molecular entities like mobocertinib to patients in China. And, when possible, ensuring submission and approval occurs in a similar timeframe as in other regions," said Lin Wang, Head of the Takeda Development Center Asia. "We’re preparing for an exciting period of growth and expansion in fiscal year 2021, with the potential for up to 12 submissions and six approvals, which will contribute significantly toward our goal of delivering more than 15 innovative medicines to patients in China by fiscal year 2024."

The NDA for mobocertinib is primarily based on results from the Phase 1/2 trial, which is evaluating the safety and efficacy of oral mobocertinib in patients with mNSCLC.

On July 7, 2021 Crescendo Biologics Ltd (Crescendo), a clinical stage immuno-oncology company developing novel, targeted T cell enhancing therapeutics, reported that senior members of the executive team will be participating at the following events (Press release, Crescendo Biologics, JUL 7, 2021, View Source [SID1234584666]). They look forward to meeting investors to discuss the Company’s business strategy, technology, discovery platform and development programmes.

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William Blair Biotech Focus Conference 2021, 14-15 July 2021
Participation in Panel II – Moving Beyond Monoclonals: The Potential of Multispecific Therapies on 14 July at 11:20 am EDT, 4:20 pm BST
Solebury Trout & Venrock’s 5th Annual EU Investor Tour, 14 July 2021
Presentation at 11:15 am EDT, 4:15 pm BST
LifeSci Private Company Summer Symposium 2021, 21 July 2021
Fireside chat at 9:25 am EDT, 2:25 pm BST
BTIG Virtual Biotechnology Conference, 10 August 2021
Fireside chat at 11:30 am EDT, 4:30 pm BST
If you would like to meet the team at these events, please contact the Company via email at [email protected].

Please refer to individual conference websites for further information and updated schedules.

On July 7, 2021 Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) reported that it filed regulatory application with the Ministry of Health, Labour and Welfare for the anti-cancer agent/humanized anti-PD-L1 monoclonal antibody Tecentriq Intravenous Infusion 1200 mg [generic name: atezolizumab (genetical recombination)] for the adjuvant treatment of non-small cell lung cancer (NSCLC) on July 6, 2021 (Press release, Chugai, JUL 7, 2021, View Source [SID1234584651]).

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"Approximately 50% of patients with early-stage lung cancer experience relapse following surgery. It is very important to prevent recurrence in order to improve the cure rate. Tecentriq is the first cancer immunotherapy which reduced the risk of disease recurrence or death in NSCLC as adjuvant therapy following surgery," said Chugai’s President and CEO, Dr. Osamu Okuda. "We are working to obtain regulatory approval to deliver Tecentriq, which has been shown to reduce the rate of recurrence or death, to patients as soon as possible as a new adjuvant treatment for early-stage lung cancer."

This filing is based on the results from phase III IMpower010 study examining Tecentriq as an adjuvant treatment in NSCLC. The study showed for the first time that treatment with Tecentriq following surgery and chemotherapy reduced the risk of disease recurrence or death (disease-free survival; DFS) by 34% (hazard ratio [HR]=0.66, 95% CI: 0.50–0.88) in people with Stage II-IIIA NSCLC, whose tumors express PD-L1≥1%, compared with best supportive care (BSC). VENTANA OptiView PD-L1 (SP263) Assay, a pathological testing kit marketed by Roche Diagnostics K.K., was used to detect PD-L1 expression. Safety data for Tecentriq were consistent with its known safety profile and no new safety signals were identified.

Pivotal Phase III data at ASCO (Free ASCO Whitepaper) show Roche’s Tecentriq helps certain people with early lung cancer live significantly longer without their disease returning (Press release by Roche issued on May 20, 2021)
View Source

About IMpower010 study
IMpower010 is a Phase III, global, multicenter, open-label, randomized study evaluating the efficacy and safety of Tecentriq compared with BSC, in participants with Stage IB-IIIA NSCLC (UICC 7th edition), following surgical resection and up to 4 cycles of adjuvant cisplatin-based chemotherapy. The study randomized 1,005 people with a ratio of 1:1 to receive either at most 16 cycles of Tecentriq or BSC. The primary endpoint is investigator-determined DFS in the PD-L1-positive Stage II-IIIA, all randomized Stage II-IIIA and ITT Stage IB-IIIA populations. Key secondary endpoints include OS in the overall study population, ITT Stage IB-IIIA NSCLC.

About non-small cell lung cancer (NSCLC)
In Japan, 130,000 people (86,800 men and 43,100 women; 2020 predicted values) are estimated to be afflicted with lung cancer each year. 75,600 people in Japan (53,200 men and 22,300 women; 2020 predicted values) die as a result of the disease. Lung cancer is the leading cause of cancer death. Lung cancer can be broadly divided into small cell lung cancer and NSCLC according to the tissue type. NSCLC has the largest number of patients, accounting for about 85% of all lung cancer cases.

About approval status of Tecentriq in Japan
Tecentriq was launched in April 2018 with an indication of unresectable, advanced or recurrent non-small cell lung cancer (NSCLC), followed by an approval for the additional dosing for the treatment of untreated unresectable, advanced or recurrent NSCLC in December 2018. In addition, an approval of extensive-stage small cell lung cancer has been obtained in August 2019, an approval of PD-L1 positive hormone receptor-negative and HER2-negative inoperable or recurrent breast cancer has been obtained in September 2019, and an approval for the additional dosing for the treatment of chemotherapy-naïve unresectable advanced or recurrent non-squamous NSCLC has been obtained in November 2019. Tecentriq was approved for the treatment of unresectable hepatocellular carcinoma in September 2020, followed by an approval for the additional dosing for the treatment of untreated PD-L1 positive, unresectable, advanced or recurrent NSCLC in December 2020.

On July 7, 2021 PureTech Health plc (Nasdaq: PRTC, LSE: PRTC) ("PureTech" or the "Company"), a clinical-stage biotherapeutics company dedicated to discovering, developing and commercializing highly differentiated medicines for devastating diseases, reported a clinical trial and supply agreement with an affiliate of BeiGene, Ltd. (Nasdaq: BGNE; HKEX: 06160) to evaluate BeiGene’s tislelizumab, an anti-PD-1 immune checkpoint inhibitor, in combination with PureTech’s LYT-200, an investigational monoclonal antibody targeting galectin-9, for the potential treatment of difficult-to-treat solid tumor indications that are associated with poor survival rates (Press release, PureTech Health, JUL 7, 2021, View Source [SID1234584667]).

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Galectin-9 is a pivotal immune modulator widely expressed in multiple difficult-to-treat tumor types and involved in the regulation of tumor promoting inflammatory and immunosuppressive pathways. Inhibition of galectin-9 with targeted antibodies leads to upregulation of immunostimulatory cytokines and anti-tumor activity in preclinical cancer models. LYT-200 is currently being evaluated as a single agent in the first phase of an adaptive Phase 1/2 clinical trial, which, based upon the trial protocol, will be followed by the portion of the trial intended to investigate LYT-200 in combination with tislelizumab. PureTech expects to report topline Phase 1 results in the fourth quarter of 2021. In addition, PureTech plans to investigate LYT-200 as a single agent and in combination with other anti-cancer treatments, including chemotherapy and other immunotherapies.

Tislelizumab is potentially differentiated from the currently approved programmed cell death protein 1 (PD-1) antibodies in an engineered fragment crystallizable region (Fc region), which in preclinical studies has been shown to minimize potentially negative interactions with other immune cells. Tislelizumab has been approved in China for four solid tumor indications and regulatory decisions are pending for two additional indications. In January 2021, BeiGene and Novartis entered into a collaboration and license agreement granting Novartis rights to develop, manufacture and commercialize tislelizumab in North America, Europe and Japan.

"After a decade of optimizing use of immuno-oncology therapies, such as the checkpoint inhibitors that have certainly provided a paradigm shift in treating malignant diseases, we in the industry are eager to advance novel breakthrough agents and combinations to serve a wider range of cancer patients. Patients need new options as the first wave of immunotherapies work only in a small percentage of them. Well thought-out combination immunotherapy regimens may be that way forward," said Aleksandra Filipovic, M.D., Ph.D., Head of Oncology at PureTech. "We believe LYT-200 has the potential to engage the immune system against what are currently intractable cancers, both as a single agent and in combination with checkpoint inhibitors. We look forward to evaluating whether LYT-200 in combination with BeiGene’s tislelizumab can improve outcomes for patients with metastatic solid tumors."

Under the terms of the agreement, PureTech will maintain control of the LYT-200 program, including global R&D and commercial rights. BeiGene has agreed to supply tislelizumab for use in combination with LYT-200.

About LYT-200
LYT-200 is a monoclonal antibody targeting a foundational immunosuppressive protein, galectin-9, for the potential treatment of solid tumors, including pancreatic ductal adenocarcinoma, colorectal cancer and cholangiocarcinoma, that are difficult to treat and have poor survival rates. PureTech has presented preclinical data demonstrating high expression of galectin-9 across breast cancer, pancreatic cancer and cholangiocarcinoma samples and found that the highest levels of galectin-9 correlated with shorter time to disease relapse and poor survival. These data suggest that galectin-9 could be significant both as a therapeutic target for solid tumors for a range of cancers and as a cancer biomarker. Preclinical animal and patient-derived organoid tumor models also showed the potential efficacy of LYT-200 and the importance of galectin-9 as a target. LYT-200 is currently being evaluated in a Phase 1/2 adaptive design trial, and results from the Phase 1 portion are expected in the fourth quarter of 2021.

About Tislelizumab
Tislelizumab (BGB-A317) is a humanized IgG4 anti-PD-1 monoclonal antibody specifically designed to minimize binding to FcγR on macrophages. In pre-clinical studies, binding to FcγR on macrophages has been shown to compromise the anti-tumor activity of PD-1 antibodies through activation of antibody-dependent macrophage-mediated killing of T effector cells. Tislelizumab is the first drug from BeiGene’s immuno-oncology biologics program and is being developed internationally as a monotherapy and in combination with other therapies for the treatment of a broad array of both solid tumor and hematologic cancers.

The China National Medical Products Administration (NMPA) has granted tislelizumab in five indications, including full approval for first-line treatment of patients with advanced squamous non-small cell lung cancer (NSCLC) in combination with chemotherapy and for first-line treatment of patients with advanced non-squamous NSCLC in combination with chemotherapy; and conditional approval for the treatment of patients with classical Hodgkin’s lymphoma (cHL) who received at least two prior therapies, for the treatment of patients with locally advanced or metastatic urothelial carcinoma (UC) with PD-L1 high expression whose disease progressed during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy, and for the treatment of patients with hepatocellular carcinoma (HCC) who have received at least one systemic therapy. Full approval for these indications is contingent upon results from ongoing randomized, controlled confirmatory clinical trials.

In addition, two supplemental Biologics License Applications for tislelizumab have been accepted by the Center for Drug Evaluation (CDE) of the NMPA and are under review for second- or third-line treatment of patients with locally advanced or metastatic NSCLC who progressed on prior platinum-based chemotherapy and for patients with previously treated, locally advanced unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) solid tumors.

BeiGene has initiated or completed 17 potentially registration-enabling clinical trials in China and globally, including 13 Phase 3 trials and four pivotal Phase 2 trials.

In January 2021, BeiGene and Novartis entered into a collaboration and license agreement granting Novartis rights to develop, manufacture, and commercialize tislelizumab in North America, Europe and Japan.

Tislelizumab is not approved for use outside of China.

On July 6, 2021 Kura Oncology, Inc. (Nasdaq: KURA), a clinical-stage biopharmaceutical company committed to realizing the promise of precision medicines for the treatment of cancer, reported a clinical collaboration with Novartis to evaluate the combination of tipifarnib and alpelisib in patients with head and neck squamous cell carcinoma (HNSCC) whose tumors have HRAS overexpression or PIK3CA mutation and/or amplification. Tipifarnib is Kura’s farnesyl transferase inhibitor drug candidate currently in a registration-directed trial as a monotherapy in patients with HRAS mutant HNSCC. Novartis’ alpelisib is an inhibitor of phosphatidylinositol-3-kinase (PI3K) with inhibitory activity predominantly against the PI3Kα isoform.

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"Our preclinical data suggest that HRAS and PI3Kα are co-dependent pathways involved in the development and maintenance of HNSCC in certain patient populations. Combining tipifarnib with alpelisib has the potential to provide a clinically meaningful increase in anti-tumor activity compared to when inhibiting either pathway alone," said Stephen Dale, M.D., Chief Medical Officer of Kura Oncology. "We believe this clinical collaboration will enable us to potentially expand the use of tipifarnib to a significantly higher percentage of patients with advanced HNSCC. We look forward to initiating the combination trial in the second half of 2021."

The Phase 1/2 KURRENT trial is a biomarker-defined cohort study designed to evaluate the safety, determine the recommended combination dosing and assess early anti-tumor activity of tipifarnib and alpelisib for the treatment of HNSCC patients whose tumors are dependent on HRAS and/or PI3Kα pathways, which is approximately 50% of HSNCC patients, according to The Cancer Genome Atlas (TCGA).

Under the collaboration, Kura maintains global development and commercial rights to tipifarnib.

About HNSCC

Head and neck squamous cell carcinoma (HNSCC) is the seventh most common cancer worldwide, accounting for more than 500,000 new cases each year. Despite advances in immunotherapy, the prognosis for advanced HNSCC patients remains poor, with an estimated median overall survival of 13-15 months in patients when stratified by PD-L1 expression. Although the anti-epidermal growth factor receptor (EGFR) antibody, cetuximab, was approved more than a decade ago, development of biomarker-directed therapies in HNSCC has been stymied by the limited number of druggable targets in the genomic landscape and the challenge of managing drug refractory recurrent/metastatic HNSCC.

About Tipifarnib

Tipifarnib, is a potent, selective and orally bioavailable inhibitor of farnesyl transferase, which has been granted Breakthrough Therapy and Fast Track Designations by the FDA for the treatment of patients with HRAS mutant HNSCC. In addition to HNSCC, tipifarnib has demonstrated encouraging clinical activity in multiple additional genetically defined tumor types. Kura has received multiple issued patents for tipifarnib, providing patent exclusivity in the U.S. and foreign countries.