On september 17, 2018 Mersana Therapeutics, Inc. (NASDAQ:MRSN), a clinical-stage biopharmaceutical company focused on discovering and developing a pipeline of antibody drug conjugates (ADCs) based on its Dolaflexin and other proprietary platforms, reported that the U.S. Food and Drug Administration (FDA) has lifted the partial clinical hold on the Phase 1 study of XMT-1522 (Press release, Mersana Therapeutics, SEP 17, 2018, View Source [SID1234529521]).

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Mersana and the FDA reached alignment on changes to the protocol, including increased monitoring as well as the exclusion of patients with advanced hepatic impairment. Although XMT-1536, Mersana’s Dolaflexin ADC targeting NaPi2b, was not subject to a clinical hold, Mersana has decided to implement similar modifications to the XMT-1536 protocol.

In addition, alternative dosing regimens will be evaluated for both clinical trials. The XMT-1522 trial will begin with a once-every-four-week dose regimen. This dosing regimen has already been implemented in the XMT-1536 trial at previously explored dose levels in order to enable a comparison of relevant doses and their impact on the safety, efficacy and PK profile of the drug candidate. The company may evaluate additional regimens as well. Data on XMT-1536 is expected in the first half of 2019.

"We are excited to resume enrollment on the XMT-1522 trial and to work with investigators to explore the full potential of both promising drug candidates in the solid tumor setting," said Anna Protopapas, Chief Executive Officer of Mersana.

About XMT-1522

XMT-1522 is a Dolaflexin ADC targeting HER2-expressing tumors. XMT-1522 contains a proprietary HER2 antibody which is conjugated with Mersana’s Dolaflexin platform — a Fleximer polymer linked with a proprietary auristatin payload. XMT-1522 provides a drug load of approximately 12 molecules per antibody, specifically designed to improve potency while simultaneously increasing tolerability. XMT-1522 has the potential to extend HER2-targeted therapy beyond the current "HER2-positive" populations into patients with lower levels of HER2 expression. The Phase 1 protocol will evaluate XMT-1522 in patients with advanced HER2-positive breast and gastric cancer, as well as advanced breast cancer with low HER2 expression and non-small cell lung cancer (NSCLC). More information on the ongoing Phase 1 clinical trial can be found at clinicaltrials.gov.

About XMT-1536

XMT-1536 is a highly potent immunoconjugate targeting the sodium-dependent phosphate transport protein (NaPi2b) and is comprised of an average of 10-15 DolaLockTM payload molecules conjugated to XMT-1535, a proprietary humanized anti-NaPi2b antibody, via the Dolaflexin ADC platform. NaPi2b is an antigen highly expressed in the majority of non-squamous NSCLC and epithelial ovarian cancer. XMT-1536 is in Phase 1 clinical trials in patients with tumors expressing NaPi2b, including ovarian cancer, NSCLC and other cancers. More information on the ongoing Phase 1 clinical trial can be found at clinicaltrials.gov.

On September 17, 2018 G1 Therapeutics, Inc. (Nasdaq: GTHX), a clinical-stage oncology company, reported that it is expediting analyses of myelopreservation data from its randomized Phase 2 trial of trilaciclib in combination with chemotherapy and Tecentriq (atezolizumab) in first-line small cell lung cancer (SCLC) (Press release, G1 Therapeutics, SEP 17, 2018, View Source [SID1234529790]). Myelopreservation results from the trial will be reported in the fourth quarter of 2018.

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"We elected to make myelopreservation the primary outcome of the randomized trilaciclib/chemotherapy/Tecentriq trial based on the strength of the first-line small cell lung cancer myelopreservation results from our randomized Phase 2 trilaciclib/chemotherapy trial, which we reported in March," said Raj Malik, M.D., Chief Medical Officer and Senior Vice President, Research and Development. "This protocol amendment, which we have discussed with U.S. and European regulatory authorities, enables us to accelerate analyses of mature myelopreservation data collected from the trilaciclib/chemotherapy/Tecentriq trial. The trial will remain blinded to investigators and participants, with no impact on our timeline to report overall survival data."

This randomized, double-blind Phase 2 trial enrolled 107 patients to receive trilaciclib or placebo in combination with chemotherapy (carboplatin + etoposide) and Tecentriq as first-line treatment for SCLC. The trial is evaluating the myelopreservation potential of trilaciclib. Myelopreservation is the ability to preserve hematopoietic stem and progenitor cell function, as well as immune system function, during chemotherapy. Anti-tumor efficacy measures including overall response rate, progression-free survival and overall survival are also being evaluated. Under the revised protocol, myelopreservation results are now the primary outcome and overall survival is being assessed as a secondary outcome. The trial completed enrollment in February 2018.

"Data from the trilaciclib/chemotherapy/Tecentriq trial have the potential to confirm the myelopreservation results observed in our randomized Phase 2 trial of trilaciclib in combination with chemotherapy. Both trials evaluated trilaciclib in first-line small cell lung cancer using the same chemotherapy backbone," said Mark Velleca, M.D., Ph.D., Chief Executive Officer. "By the end of the year we will have myelopreservation data from all four randomized Phase 2 trials of trilaciclib, including three in small cell lung cancer and one in triple negative breast cancer. In these trials, trilaciclib was used in first-, second- and third-line settings in combination with a variety of chemotherapy regimens. We plan to discuss the totality of the data, which includes approximately three hundred participants who received trilaciclib, with U.S. and European regulatory authorities in the first half of 2019."

Webcast and Conference Call

The G1 management team will host a webcast and conference call at 8:30 a.m. ET today to discuss the trilaciclib clinical development program. The live call may be accessed by dialing 866-763-6020

About Trilaciclib

Trilaciclib is a first-in-class myelopreservation therapy designed to preserve hematopoietic stem and progenitor cell function, as well as immune system function, during chemotherapy. Trilaciclib is a short-acting intravenous CDK4/6 inhibitor administered prior to chemotherapy and has the potential to significantly improve treatment outcomes.

Trilaciclib is being evaluated in four randomized Phase 2 clinical trials. In March 2018, G1 announced positive Phase 2 data showing myelopreservation benefits in newly diagnosed, treatment-naive small cell lung cancer (SCLC) patients (NCT02499770). Additional results from this trial will be reported at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2018 Congress being held October 19-23. The company plans to report data from three other randomized Phase 2 trials in 2018: a trial in combination with chemotherapy and Tecentriq in first-line SCLC, (NCT03041311), a trial in combination with chemotherapy in previously treated SCLC (NCT02514447), and a trial in combination with chemotherapy in triple-negative breast cancer (NCT02978716).

On September 17, 2018 Inspyr Therapeutics reported that it has entered into an agreement with Ridgeway Therapeutics Inc. in which Ridgeway will license and assume control of certain assets relating to Inspyr’s oncology development programs, including intellectual property rights relating to adenosine antagonists owned by Inspyr (Press release, Inspyr Therapeutics, SEP 17, 2018, View Source [SID1234568253]).

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Adenosine receptors have a variety of functions in the body that are expressed through four subtypes (A1, A2A, A2B, and A3). The adenosine A2 receptor subtypes (A2R) are of particular interest as potential targets for the treatment of cancer. Extremely high levels of adenosine are found locally in the tumor microenvironment. These have a direct immunosuppressive effect on T-cells and other cell types that would otherwise attack and kill cancer cells. Inhibition of the A2R has the potential to reverse these immunosuppressive effects.

Inspyr and Ridgeway will collaborate on certain aspects of development which will include a minimum level of purchased services by Ridgeway within 18 months of this transaction. In addition, Inspyr is eligible for approximately $12 million in success-based milestones from the Transaction. Inspyr is also entitled to receive royalties on all commercial sales. In the event Ridgeway sub-licenses these assets, Inspyr is entitled to share in the proceeds of any future transaction.

On September 17, 2018 Halozyme Therapeutics, Inc. (NASDAQ: HALO) reported that Roche has received approval from Health Canada for a subcutaneous (SC) formulation of trastuzumab (Herceptin SC) for the treatment of patients with HER2-positive breast cancer (Press release, Halozyme, SEP 17, 2018, View Source [SID1234529462]). This is a co-formulation with Halozyme’s proprietary recombinant human hyaluronidase enzyme (ENHANZE technology).

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"We are pleased that the subcutaneous formulation of trastuzumab (Herceptin SC) has been approved in Canada," said Dr. Helen Torley, president and chief executive officer. "Patients and health care providers will now have another treatment option with the potential for a reduced administration time."

The U.S. Food and Drug Administration accepted a Biologics License Application from Genentech for a subcutaneous (SC) formulation of trastuzumab (Herceptin SC) in July 2018.

About ENHANZE Technology
Halozyme’s proprietary ENHANZE drug-delivery technology is based on its patented recombinant human hyaluronidase enzyme (rHuPH20). rHuPH20 has been shown to remove traditional limitations on the volume of biologics that can be delivered subcutaneously (just under the skin). By using rHuPH20, some biologics and compounds that are administered intravenously may instead be delivered subcutaneously. ENHANZE may also benefit subcutaneous biologics by reducing the need for multiple injections. This delivery has been shown in studies to reduce health care practitioner time required for administration and shorten time for drug administration.

On September 17, 2018 Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for cancer and immune disorders, reported that it has entered into a collaboration with ONO Pharmaceutical Co., Ltd. for the joint development and commercialization of two off-the-shelf CAR-T cell product candidates (Press release, Fate Therapeutics, SEP 17, 2018, View Source [SID1234529463]). Using Fate Therapeutics’ proprietary induced pluripotent stem cell (iPSC) product platform, the two CAR T-cell collaboration candidates will each be derived from a clonal master iPSC line engineered to completely eliminate endogenous TCR expression, insert a chimeric antigen receptor (CAR) into the TRAC locus and incorporate other anti-tumor functionality. This transformative approach enables the cost-effective production of cell-based cancer immunotherapies that are uniformly engineered, extensively characterized and homogeneous in composition, and can be consistently and repeatedly mass produced and delivered to patients in an off-the-shelf manner.

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"We are delighted to collaborate with ONO, a global leader in oncology with a long history of developing innovative breakthrough cancer drugs," said Scott Wolchko, President and Chief Executive Officer of Fate Therapeutics. "This partnership with ONO enables Fate to further enhance its expertise in targeting solid tumors and to accelerate the global development of our pipeline of off-the-shelf, iPSC-derived CAR-T cell product candidates."

Under the terms of the strategic option agreement, Fate Therapeutics and ONO will jointly advance each iPSC-derived CAR-T cell collaboration candidate to a pre-defined preclinical milestone. The first iPSC-derived CAR T-cell candidate targets an antigen expressed on certain lymphoblastic leukemias, and Fate Therapeutics retains global responsibility for development and commercialization with ONO having an option to assume responsibilities in Asia. The second candidate targets a novel antigen identified by ONO expressed on certain solid tumors, with ONO having an option to assume global responsibility for further development and commercialization and Fate Therapeutics retaining the right to co-develop and co-commercialize the candidate in the United States and Europe. For both collaboration candidates, Fate Therapeutics retains manufacturing responsibilities on a global basis.

"ONO identified Fate Therapeutics as the partner of choice for the generation of off-the-shelf CAR T-cell cancer immunotherapies in our portfolio," said Hiromu Habashita, Corporate Officer, and Executive Director of Discovery & Research of ONO. "We are excited to work with Fate Therapeutics and apply its industry-leading iPSC product platform to develop and deliver the next-generation of CAR T-cell therapies for cancer patients."

Fate Therapeutics will receive an upfront payment and committed research funding during the preclinical option period, and is eligible to receive a preclinical option exercise fee, clinical, regulatory and commercialization milestone payments and tiered royalties on net sales by ONO in connection with the development and commercialization of each collaboration product by ONO in the ONO territory