On January 13, 2020 Turning Point Therapeutics, Inc. (NASDAQ: TPTX), a precision oncology company developing next-generation therapies that target genetic drivers of cancer, reported that program updates for its four drug candidates and ongoing clinical studies (Press release, Turning Point Therapeutics, JAN 13, 2020, View Source [SID1234564381]).

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"Following a transformational year in 2019, we are pleased with the progress in our ongoing clinical studies, our recent Fast Track designation for repotrectinib and nomination of our ALK inhibitor candidate for IND-enabling studies," said Athena Countouriotis, M.D., president and CEO.

"In addition, we have now dosed multiple patients with our RET/SRC-inhibitor, TPX-0046, who presented with solvent-front mutations and were previously treated with other investigational RET inhibitors. The emergence of RET solvent-front mutations is an indication of the need for a next-generation RET inhibitor given the limited treatment options for these patients."

PROGRAM UPDATES AND 2020 MILESTONES

Repotrectinib
Clinical study of repotrectinib continues to progress in the Phase 2 registrational portion of the TRIDENT-1 global study and Phase 1/2 study in pediatric patients. With sites activating globally in the TRIDENT-1 study, the company continues to anticipate reporting early interim data from initial patients in some of the registrational cohorts in the second half of the year.

The company announced today that repotrectinib has been granted Fast Track designation by the U.S. Food and Drug Administration for the treatment of ROS1-positive advanced non-small cell lung cancer (NSCLC) patients who have been previously treated with one prior line of platinum-based chemotherapy and one prior line of a ROS1 tyrosine kinase inhibitor (TKI). There are currently no approved targeted therapies for TKI-pretreated ROS1-positive NSCLC patients.

Following ongoing dialogue with health authorities, the company recently amended the TRIDENT-1 protocol for expansion cohorts 2 and 3 to clarify that ROS1-positive advanced NSCLC patients must have had one prior platinum-based chemotherapy regimen in addition to one prior TKI (cohort 2) or two prior TKIs (cohort 3). This amendment to cohort 2 is in line with the patient population granted fast track designation. Additionally, based on the potential future treatment paradigm, expansion cohort 4 has been amended to enroll only ROS1-positive advanced NSCLC patients with one prior TKI and no prior chemotherapy. This amendment is aimed at expanding enrollment in multiple ROS1-positive advanced NSCLC TKI-pretreated patient populations.

TPX-0022 – MET/CSF1R/SRC Inhibitor
Study of TPX-0022 continues to progress in a Phase 1 clinical trial in advanced solid tumor patients with MET genetic alterations. The company continues to anticipate reporting early interim data from initial patients during the second half of the year.

TPX-0046 – RET/SRC Inhibitor
Study of TPX-0046 continues to progress in a Phase 1/2 clinical trial, with early enrollment including multiple RET-positive patients with solvent-front mutations previously treated with other investigational RET inhibitors. In preclinical studies against proxy molecules for other investigational RET inhibitors, TPX-0046 showed comparable or stronger potency against wildtype and certain RET solvent-front mutations.

TPX-0131, A Next-Generation ALK Inhibitor
The company reported the advancement of TPX-0131, its next-generation ALK inhibitor candidate, into IND-enabling studies. TPX-0131 has been designed with a compact macrocyclic structure and in preclinical studies has been shown to potently inhibit wildtype ALK and numerous ALK mutations, in particular the clinically observed G1202R solvent-front mutation and G1202R/L1196M compound mutation. ALK-driven tumors are estimated to represent up to 7 percent of driver oncogenes in NSCLC and of patients who develop a resistance mutation, G1202R has been reported in approximately 42 percent.

2020 Milestones
Key milestones anticipated in 2020 include:

Additional TPX-0131 preclinical data during the first half of the year;
Present preclinical repotrectinib combination data;
Early interim data from initial patients in some of the registrational cohorts of the repotrectinib TRIDENT-1 Phase 2 study during the second half of the year;
Early interim data from initial patients treated with TPX-0022 during the second half of the year; and
Submitting the IND for TPX-0131 by early 2021.

On January 13, 2020 Oncternal Therapeutics Presented the Corporate Presentation (Presentation, Oncternal Therapeutics, JAN 13, 2020, View Source [SID1234554377]).

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On January 13, 2020 Personalised cancer treatment is one step closer to becoming a reality for more patients, thanks to a Cancer Council Beat Cancer Project grant awarded to University of South Australia researcher Dr Stephanie Reuter Lange to explore how computer-based modelling can optimise cancer treatment and remove the need for expensive clinical trials (Press release, University of South Australia, JAN 13, 2020, View Source [SID1234554068]).

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Dr Reuter Lange’s $300,000 project is one of two UniSA projects successful in today’s Cancer Council Beat Cancer Project funding announcement with Professor Peter Hoffmann also securing $100,000 to further critical work in identifying the extent of endometrial cancer and where it has spread.

While cancer treatments are most successful when personalised to an individual, Dr Reuter Lange says most cancer medicines are still administered with a "one size fits all" approach.

"Despite substantial improvements in the treatment of cancer, three out of 10 patients will still not survive longer than five years, due to either cancer progression or death from severe treatment-related side effects," Dr Reuter Lange says.

"There is no field of medicine in which individualisation of medicines is more important than in the area of oncology. There is large variability in how patients respond to many cancer medicines, which can result in either undertreatment that leads to cancer progression, or overtreatment that can have significant toxic side effects.

"The concept of dose individualisation means we can tailor the amount of a drug administered to an individual patient to maximise tumour response and minimise side effects. My focus will be to use computer-based modelling methods to identify dose individualisation strategies for best treatment practice."

While the merits of individualised drug dosages are clear, conducting the large-scale clinicial trials required to implement the treatment in practice is a complex and costly process which means cancer treatments currently on offer remain standardised rather than personalised.

Dr Reuter Lange’s work uses the science of mathematical and stasitical models to characterise drug behaviour, helping clinicians make an educated decision on the most appropriate treatment regimes.

"This work will provide an evidence-basis for dose individualisation of cancer therapies, offsetting the need for the conduct of costly, large-scale clinical trials," she says.

"Ultimately this work will lead to improved patient outcomes and provide a framework on which treatment guidelines can be based for the optimal use of new and existing cancer therapies."

UniSA Professor Hoffmann’s research project will focus on developing less intrusive diagnosis and treatment techniques for endometrial cancer, the most diagnosed gynaecological cancer in Australia.

According to Professor Hoffmann, radiological imaging is unreliable in determining the stage of endometrial cancer, meaning the majority of patients have to undergo surgical staging (and removal of lymph nodes) even though the minority will actually have cancer that has spread to the lymph nodes (metastatic disease).

He says the Cancer Council SA funding will go towards identifying molecular tissue markers that indicate the presence of metastatic disease so that future patients may not need to undergo unnecessary radical surgery (Lymphadenectomy) to get an accurate diagnosis.

Established in 2011 Cancer Council’s Beat Cancer Project is a collaboration between Cancer Council SA, the State Government, SAHMRI and the universities and providing research funding to improve the lives of all South Australians impacted by cancer. For more information on the project, go to cancersa.org.au/research/beat-cancer-project.

On January 13, 2019 CNS Pharmaceuticals, Inc. (NASDAQ: CNSP) ("CNS" or the "Company"), a biotechnology company specializing in the development of novel treatments for brain tumors, reported it has entered into a licensing agreement with The University of Texas MD Anderson Cancer Center (Press release, CNS Pharmaceuticals, JAN 13, 2020, View Source [SID1234553603]). The agreement grants Company the right to develop and commercialize WP1244, a new class of DNA-binding agent designed to cross the blood-brain barrier for the potential treatment of primary and metastatic brain cancers.

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This agreement allows for the continued development of WP1244, which has been shown to have high anti-tumor activity in preclinical studies. WP1244 was designed using a "modular" strategy, which combines intercalation and groove-binding modes into molecules with the requisite chirality and binding-site size to impart meaningful selectivity. Previous pre-clinical tests have demonstrated the agent’s ability to cross the blood-barrier in animal models with no acute clinically observable toxicity.

"Our licensing agreement has allowed CNS to double its portfolio with the addition of WP1244. We are extremely excited to continue the development of this entirely new class of DNA-binding agent," stated CEO of CNS, John M. Climaco. "We believe the compound demonstrates enormous potential through its novel mechanism of action, ability to cross the blood-brain barrier, and tremendous potency, 500 times that of classic DNA binding agents such as daunorubicin. WP1244 has shown to be mechanistically and biologically novel and selective, and its addition to our pipeline furthers our goal of being the leading developer of organ-targeted cancer therapeutics."

About WP1244

WP1244 is a novel DNA binding agent with relatively high molecular weight (981.3 MW) having a polyamide moiety attached to the amino sugar. WP1244 is exceedingly potent having in vitro IC50 values in the subnanomolar range and is currently being studied for its therapeutic potential in preclinical studies. A previous 5-mouse pilot study performed with WP1244 confirmed the presence of WP1244 in murine brain tissue. WP1244 was designed utilizing a "modular" design strategy, which combines intercalation and groove-binding modes into molecules with the requisite chirality and binding-site size to impart meaningful selectivity. Pre-clinical studies of WP1244 have demonstrated its potential ability to cross the blood-brain barrier in animal models. WP1244 was developed at The University of Texas MD Anderson Cancer Center.

On January 13, 2020, Coherus BioSciences, Inc. (the "Company") reported that it has entered into a license agreement (the "License Agreement") with Innovent Biologics (Suzhou) Co., Ltd. ("Innovent") for the development and commercialization of a biosimilar version of bevacizumab (Avastin) in any dosage form and presentations ("bevacizumab Licensed Product") in the United States and Canada (the "Territory") (Filing, 8-K, Coherus Biosciences, JAN 13, 2020, View Source [SID1234553226]). Under the License Agreement, Innovent granted to the Company an exclusive, royalty-bearing license to develop and commercialize the bevacizumab Licensed Product in the field of treatment, prevention or amelioration of any human diseases and conditions as included in the label of Avastin. Under the License Agreement, the Company also acquired an option to develop and commercialize Innovent’s biosimilar version of rituximab (Rituxan) in any dosage form and presentations (the "rituximab Licensed Product" and together with the bevacizumab Licensed Product, the "Licensed Products") in the Territory. Subject to the terms of the License Agreement, the Company may exercise its option within 12 months of its receipt of certain regulatory materials from Innovent. Following the Company’s option exercise, Innovent’s biosimilar version of rituximab would be deemed a Licensed Product for all purposes of the License Agreement and Innovent would grant to the Company an exclusive, royalty-bearing license to develop and commercialize Innovent’s biosimilar version of rituximab in the field of treatment, prevention or amelioration of any human diseases and conditions as included in the label of Rituxan.

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Innovent will supply the Licensed Products to the Company in accordance with a manufacturing and supply agreement to be executed by the parties. Under the License Agreement, the Company acquired the right to require Innovent to perform technology transfer for the manufacturing of the Licensed Products in the Territory and, upon completion of such technology transfer, the Company will have the exclusive right to manufacture the Licensed Products in the Territory.

The Company will pay Innovent an upfront payment of $5,000,000. Additionally, the Company is obligated to pay Innovent an aggregate of up to $40,000,000 in milestone payments in connection with the achievement of certain development, regulatory and sales milestones with respect to the bevacizumab Licensed Product and, if the Company’s option is exercised, an aggregate of up to $40,000,000 in milestone payments in connection with the achievement of certain development, regulatory and sales milestones with respect to the rituximab Licensed Product. The Company will share a percentage of net sales of Licensed Products with Innovent in the mid-teens to low twenty percent range. If the Company exercises its option, it would be required to pay an option exercise fee of $5,000,000. Subject to the terms of the License Agreement, if the Company requests Innovent to perform technology transfer for the manufacturing of the Licensed Products, it would be required to pay up to $10,000,000 for fees related thereto.

For the bevacizumab Licensed Product, the License Agreement’s initial term continues in effect for ten years after the effective date of the License Agreement, and thereafter renews for successive two year periods upon mutual agreement by the parties, unless otherwise terminated in accordance with its terms. For the rituximab Licensed Product, the License Agreement’s initial term would continue in effect for ten years after the effective date of the option effective date and thereafter would renew for successive two year periods upon mutual agreement by the parties, unless otherwise terminated in accordance with its terms. Either party may terminate the License Agreement for the other party’s material breach that is not cured within a specified time period or for the other party’s bankruptcy or insolvency-related events. Innovent may terminate the License Agreement if the Company undergoes a change of control with a competitor of Innovent and does not assign the License Agreement to a third party within a certain period of time. On a Licensed Product-by-Licensed Product basis, the Company may terminate the License Agreement based on certain market conditions beginning 12 months after the first commercial sale of such Licensed Product with 18 months advance written notice. Also on a Licensed Product-by-Licensed Product basis, the Company may terminate the License Agreement in certain circumstances of delays, or anticipated delays, in the achievement of regulatory approval of such Licensed Product in the United States, if the Company receives certain adverse regulatory feedback from the U.S. Food and Drug Administration ("FDA") for such Licensed Product, or if the Company receives written FDA meeting minutes indicating that the FDA recommends an additional phase 3 clinical trial efficacy comparability study to support the regulatory approval of such Licensed Product in the United States.