On January 8, 2018 TG Therapeutics, Inc. (NASDAQ:TGTX) (or "TG") and Jiangsu Hengrui Medicine Co., Ltd. (SSE:600276) (or "Hengrui") reported that the companies have entered into an exclusive global license agreement pursuant to which TG Therapeutics will obtain worldwide rights, excluding Asia but including Japan, for the development of Hengrui’s Bruton’s Tyrosine Kinase (BTK) inhibitor program, including lead candidate TG-1701 (known in China as SHR-1459), as monotherapy and in combination with ublituximab (TG-1101), TG’s glycoengineered anti-CD20 monoclonal antibody, and umbralisib (TGR-1202), TG’s next generation PI3K-delta inhibitor (Press release, TG Therapeutics, JAN 8, 2018, View Source [SID1234523028]). In addition to TG-1701, the global license agreement covers TG-1702 (SHR-1266), another BTK inhibitor in pre-clinical development.

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Under the terms of the agreement, Hengrui will receive an up-front licensing fee and near-term milestones, payable in TG common stock, and will be eligible to receive additional payments contingent on certain clinical, regulatory, and commercial milestones, totaling approximately $350MM, as well as tiered royalties on net sales.

TG-1701 (SHR-1459) and TG-1702 (SHR-1266) are orally available, covalently-bound BTK inhibitors that exhibit superior selectivity to BTK compared to ibrutinib in in vitro kinase screening. Hengrui commenced a Phase 1 clinical trial for TG-1701 (SHR-1459) in China in December 2017 while TG-1702 (SHR-1266) is in pre-clinical development.

Previously, TG reported that the triple combination of ublituximab, umbralisib, and the BTK inhibitor ibrutinib, resulted in a 100% Overall Response Rate (ORR) among 19 treated patients with Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL), an 86% ORR among 7 treated patients with iNHL (Follicular Lymphoma and Marginal Zone Lymphoma) and 100% ORR in the 4 treated patients with Mantle Cell Lymphoma (MCL).

Michael S. Weiss, Executive Chairman and Chief Executive Officer of TG Therapeutics stated, "We are pleased to be partnering with one of the leading Chinese biopharmaceutical companies. We have been evaluating potential BTK inhibitors for quite some time and we were really impressed with Hengrui’s research that led to the development of these two highly selective BTK inhibitors. We believe TG-1701 could be comparable to the best-in-class BTK inhibitors and in combination with ublituximab and umbralisib, could represent a truly unique triple combination treatment option across CLL and NHL." Mr. Weiss continued, "With our UNITY program, we have pivotal and registration directed trials either already fully enrolled or enrolling across CLL and NHL for our U2 combination of umbralisib + ublituximab, and for umbralisib as a single agent. With this license, we have taken a major step toward the development of a next generation, wholly-owned, proprietary, triplet therapy. Our goal is to advance TG-1701 into the clinic as quickly as possible in the first half of this year."

"TG Therapeutics has a distinctive strategy towards addressing B-cell lymphomas, employing unique combination strategies to harness key drivers of oncogenesis based on a portfolio of differentiated assets," said Lianshan Zhang, Ph.D., President of Global R&D of Hengrui. "We have been very impressed by the leadership at TG Therapeutics and their vision in re-defining the treatment landscape for lymphoma patients."

"Our steadfast commitment towards providing better and safer medicines for patients has propelled Hengrui to be a leading biopharmaceutical company in China," said Piaoyang Sun, Ph.D., Chairman of Hengrui. "In recent years we have worked hard to generate and develop novel, potentially high impact oncology assets across modalities including immuno-oncology, targeted therapies, hormonal therapies, antibody-drug conjugates, oncolytic viruses, and epigenetics, among others. Hengrui is absolutely delighted to be a partner of TG Therapeutics to jointly make a difference for patients who suffer hematology malignancies around the world."

ABOUT BTK INHIBITORS

Bruton’s tyrosine kinase (BTK) is an essential component of the B-cell receptor signaling pathways that regulate the survival, activation, proliferation, and differentiation of B lymphocytes. Targeting BTK with small molecule inhibitors has been demonstrated to be an effective treatment option for B-cell lymphomas and autoimmune diseases.

On January 8, 2018 Five Prime Therapeutics, Inc. (Nasdaq:FPRX), a biotechnology company discovering and developing innovative immuno-oncology protein therapeutics, reported that it has achieved a milestone for the first Investigational New Drug (IND) application to the U.S. Food and Drug Administration by Bristol-Myers Squibb Company (BMS) (NYSE:BMY) for a therapeutic candidate under the immune checkpoint pathway discovery collaboration between the companies (Press release, Five Prime Therapeutics, JAN 8, 2018, View Source [SID1234522980]). The first clinical candidate from the collaboration is a fully-human monoclonal antibody targeting TIM-3 (T-cell immunoglobulin and mucin domain-3), an immune checkpoint receptor that is known to limit the duration and magnitude of T-cell responses1. This first IND application triggers a $5 million milestone payment to Five Prime.

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"We are excited to see Bristol-Myers Squibb file an IND for the first innovative immuno-oncology therapeutic candidate to advance to the clinic under our immuno-oncology discovery collaboration," said Bryan Irving, Ph.D. Senior Vice President, Research at Five Prime. "TIM-3 is thought to inhibit the response of T cells and other crucial immune cell types, so blocking this checkpoint pathway could be a promising component of an immuno-oncology strategy to treat a variety of tumors."

Under the terms of the discovery collaboration agreement, BMS has exclusive, worldwide rights to develop and commercialize products directed toward certain protein targets in three checkpoint pathways. Five Prime is eligible to receive up to $300 million in future development, regulatory and sales-based milestone payments for each collaboration target, including TIM-3. Five Prime is also eligible to receive tiered royalties starting from mid-single-digit increasing to low-double-digit percentages of global net sales of each product commercialized by BMS.

In addition, BMS has exercised its option to further extend the research term of the collaboration between the companies for the discovery, development and commercialization of immuno-oncology (I-O) therapies directed toward targets in two additional undisclosed immune checkpoint pathways. BMS has elected to extend the research term to March 2019 and will provide additional funding to Five Prime for the extended term. This is the second extension to the original collaboration term under the agreement that was established in March 2014.

BMS will continue to utilize Five Prime’s discovery capabilities to advance the immune checkpoint programs, including to identify and select drug candidates for preclinical development. Drug candidates developed against targets in these pathways may be studied either as single agents or in combination with approved BMS immuno-oncology therapies or others in development.

On January 8, 2018 Oncoceutics, Inc. reported that the Japanese Patent Office (JPO) has issued Japanese Patent No. 6132833 for the use of ONC201 to treat all cancers or patients having a risk of cancer, including brain, colon, breast, colorectal cancers, and glioblastoma (Press release, Oncoceutics, JAN 8, 2018, https://oncoceutics.com/oncoceutics-extends-ip-coverage-japan-new-patent-covering-cancers/ [SID1234558374]). The claims issued also include the use of ONC201 when administered in conjunction with another anticancer agent and 25 routes of administration, including oral administration.

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This is the first patent issued outside the United States covering ONC201. This patent, combined with issued patents for ONC201 formulation and use in combination with other therapies, as well as FDA regulatory designations that ONC201 has received, provides ONC201 with a robust suite of intellectual property.

ONC201, a member of the imipridone family, has demonstrated anti-cancer activity and safety in preclinical models and ongoing clinical trials, including a trial for various solid and liquid tumors. Oncoceutics has also received patents covering its next generation of imipridones, namely ONC206 and ONC212.

"We are delighted that the Japanese Patent Office has recognized these indications as novel uses of ONC201 and granted these broad patent protections in such an important market," said Martin Stogniew, Ph.D., Chief Development Officer of Oncoceutics. "The company’s current patent estate gives Oncoceutics more than 15 years of patent protection for the vast majority of human cancers, including tumor types where ONC201 is currently in Phase II trials."

On January 8, 2018 Karyopharm presented Corporate Presentation current as of January 8, 2018 (Presentation, Karyopharm, JAN 8, 2018, View Source [SID1234522975]).

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On January 8, 2018 Adaptimmune Therapeutics plc (Nasdaq:ADAP), a leader in T-cell therapy to treat cancer, reported initial safety data from its two ongoing pilot studies of SPEAR T-cells targeting MAGE-A10, one in non-small cell lung cancer (NSCLC) and a triple tumor study in bladder, melanoma, and head & neck cancers (Press release, Adaptimmune, JAN 8, 2018, View Source;p=RssLanding&cat=news&id=2325398 [SID1234522943]).

To date, 8 patients have each received 100 million transduced MAGE‑A10 SPEAR T-cells in the first dose cohorts of both studies. No evidence of toxicity related to off-target binding or alloreactivity has been observed. There have been no reports of neurotoxicity safety events similar to CAR‑T cell-related encephalopathy syndrome (CRES)1. In the NSCLC study, there has been one serious adverse event of cytokine release syndrome (CRS), a Grade 4 event that resolved with treatment. This event led to cohort 1 expansion from 3 to 6 patients. No dose limiting toxicities were observed in cohort 1 of the triple tumor study.

Following review by the independent safety review committee (SRC), the decision has been made to escalate to the next dose of 1 billion transduced MAGE-A10 SPEAR T-cells in the triple tumor study. This was the therapeutic threshold dose observed with SPEAR T‑cells targeting NY-ESO in the synovial sarcoma pilot study. The decision to escalate in the NSCLC cohort will be reviewed by the SRC following dosing of the 6th patient.

"These safety results, with one of our wholly-owned SPEAR T-cell treatments, and the upcoming escalation to the next dose in the triple tumor study are significant as they allow us to progress treating patients in these studies at a potentially active cell dose," said Rafael Amado, Adaptimmune’s Chief Medical Officer. "As data accumulate throughout 2018, we will continue to share meaningful safety and efficacy data from the MAGE-A10 and MAGE-A4 programs at relevant scientific venues."

Details about Ongoing Trials with SPEAR T-cells Targeting MAGE-A10
There are two ongoing clinical trials with SPEAR T-cells targeting MAGE-A10; one in non-small cell lung cancer (NSCLC), and a triple tumor study in bladder, melanoma, and head & neck cancers. Both studies are dose escalation trials that evaluate three doses of transduced SPEAR T-cells, administered after a lymphodepleting chemotherapy regimen. The three doses being evaluated are 100 million, 1 billion and 1 to 5 billion transduced SPEAR T-cells.

NSCLC study: In this study, five patients have received SPEAR T-cells in the first group of Cohort 1 (1a without fludarabine) 2, and there was one report of Grade 4 CRS that resolved with treatment.

Triple Tumor Study: Three patients have been dosed in the first cohort. There were no reports of CRS greater or equal to Grade 3, and all cases resolved with supportive treatment.