On May 20, 2019 Rainier Therapeutics, Inc., a privately-held clinical stage drug development company, reported the presentation of data from its FIERCE-22 trial where vofatamab, the company’s lead therapeutic stimulates an increase in immune cell activation in patients with metastatic bladder cancer (Press release, Rainier Therapeutics, MAY 20, 2019, View Source [SID1234536488]). The data is being presented in an oral and poster presentation at the 2019 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Bladder Cancer: Transforming the Field Special Conference.

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Researchers at John Hopkins School of Medicine and MD Anderson analyzed RNA from 22 paired biopsy samples from metastatic bladder cancer patients enrolled in Rainier’s Phase 1b / 2 FIERCE-22 trial. Patients who had progressed following platinum-based chemotherapy but had not received prior immune checkpoint inhibitor therapy were eligible to enroll. Tumor biopsies were taken pre- and post-treatment with vofatamab, and prior to the start of combination treatment with pembrolizumab. Patient biopsies were taken to understand changes to gene signatures induced with vofatamab and to correlate this with clinical outcomes.

"The unique design of the trial allowed us to evaluate the effect of FGFR3 inhibition on gene signatures," said David McConkey, Ph.D., John Hopkins School of Medicine. "Vofatamab, an FGFR3 specific antibody, significantly upregulated genes associated with inflammation in both wild-type and FGFR3 mutant tumors. This was associated with an increased response rate to the combination with pembrolizumab in these patients and was particularly marked in patients with luminal biology."

"Tumors that are immunologically ‘cold’ tend to exist in luminal bladder cancer and these patients have historically responded poorly to checkpoint inhibitors. The enhanced response rate seen suggests this combination may provide a valuable new treatment option," said Graeme Currie, Ph.D., Chief Operating Officer, Rainier Therapeutics. "We look forward to presenting interim clinical data from FIERCE-22 at the upcoming 2019 ASCO (Free ASCO Whitepaper) annual meeting."

Key Findings:

Compared to historical data with pembrolizumab, response rates with vofatamab treatment appear higher.
Vofatamab responders had upregulation of genes associated with an inflammatory response in the tumor.
Responses were enriched in the cohort with a luminal gene expression profile (also referred to as "immunologically cold").
About Vofatamab

Vofatamab (formerly B-701) is an antibody specifically targeted against the fibroblast growth factor receptor 3 (FGFR3), a known driver of bladder and potentially other FGFR-driven cancers. Vofatamab is the most advanced targeted antibody specific for FGFR3 known by Rainier Therapeutics to be in clinical development. Vofatamab is currently being evaluated in two clinical trials: FIERCE-22 and FIERCE-21.

FIERCE-22 is a Phase 2 trial evaluating vofatamab in combination with pembrolizumab, an immune checkpoint inhibitor, to determine safety, tolerability and efficacy in the treatment of patients with locally advanced or metastatic bladder cancer, who have progressed following platinum-based chemotherapy and who have not received prior immune checkpoint inhibitor therapy. For additional information on FIERCE-22, please visit www.clinicaltrials.gov (NCT03123055).

On May 20, 2019 Constellation Pharmaceuticals, Inc. (Nasdaq: CNST) reported that Dr. Patricia Keller, Senior Scientist at Constellation Pharmaceuticals, presented a poster titled Targeting epigenetic dysregulation in bladder cancer through inhibition of EZH2 at the Bladder Cancer: Transforming the Field meeting of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) in Denver on May 19 (Press release, Constellation Pharmaceuticals, MAY 20, 2019, View Source [SID1234536473]).

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The poster discusses results of Constellation’s work with its second-generation EZH2 inhibitor CPI-0209 in bladder cancer models, exploring whether ARID1A mutation status affected responsiveness to CPI-0209 treatment. ARID1A, a protein that is a key component of the SWI/SNF chromatin remodeling complex, is mutated in about 25% of muscle-invasive bladder cancers.

Constellation used CPI-0209 in long-term phenotypic growth assays in a panel of 21 bladder cancer cell lines, demonstrating preferential treatment sensitivity that correlated with increased cell death in cell lines harboring ARID1A mutations. Transcriptional profiling after CPI-0209 treatment showed widespread activation of EZH2 target gene expression. In vivo, once-daily treatment with CPI-0209 in bladder cell-line derived xenografts harboring ARID1A mutations produced dose-dependent tumor growth inhibition and regression. Treatment with CPI-0209 and the chemotherapeutic agent cisplatin demonstrated combinatorial effects on cell viability in vitro and on tumor growth in vivo. The poster can be viewed in the Investors & Media/Presentations section of our website.

On May 20, 2019 Imago BioSciences, Inc., a clinical-stage biotechnology company developing innovative treatments for myeloid diseases, reported that an abstract describing clinical data regarding their lysine-specific demethylase (LSD1) inhibitor has been selected for an oral presentation at the 24th Congress of the European Hematology Association (EHA) (Free EHA Whitepaper) to be held in Amsterdam, The Netherlands from June 13-16, 2019 (Press release, Imago BioSciences, MAY 20, 2019, View Source [SID1234536489]). The abstract was published on the EHA (Free EHA Whitepaper) website.

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Title: A Phase 2A Study of the LSD1 Inhibitor IMG-7289 For the Treatment of Myelofibrosis
Abstract Number: S832
Date: Saturday, June 15
Time: 12:30-12:45 CEST
Location: Elicium 2

The abstract represents the first report of clinical data on IMG-7289. The protocol of IMG-7289-CTP-102 is an ongoing Phase 1/2a clinical trial of LSD1 inhibitor IMG-7289 in patients with high or intermediate-2 risk myelofibrosis resistant to or intolerant of approved therapy (see clinicaltrials.gov NCT03136185).

In accordance with EHA (Free EHA Whitepaper) policies, abstracts submitted to the Annual Congress of EHA (Free EHA Whitepaper) are embargoed from the time of submission. The terms and conditions for presentation at the Annual Congress of EHA (Free EHA Whitepaper) prohibit any additional disclosure of data or information to be presented at the Annual Congress to be made public before the presentation.

Following the Annual Congress of EHA (Free EHA Whitepaper), a summary of the presentation will be available in the "News" section of Imago’s website.

About IMG-7289

IMG-7289 is a small molecule discovered by Imago BioSciences that inhibits lysine-specific demethylase 1 (LSD1 or KDM1A), an enzyme regulating cytokine expression and sustaining self-renewal in malignant hematopoietic stem/progenitor cells. In non-clinical studies, IMG-7289 demonstrated robust in vivo efficacy as a single agent and in combination with other therapeutic agents across a range of myeloid malignancies models including the myeloproliferative neoplasms which encompass myelofibrosis, essential thrombocythemia and polycythemia vera. IMG-7289 also shows activity against solid tumors in combination with other checkpoint agents in non-clinical models. IMG-7289 is under evaluation for the treatment of acute myeloid leukemia (see clinicaltrials.gov NCT02842827).

On May 17, 2019 AbbVie (NYSE: ABBV), a research-based global biopharmaceutical company, reported the Phase 3 INTELLANCE-1 study of depatuxizumab mafodotin (Depatux-M, previously known as ABT-414) in patients with newly diagnosed glioblastoma (GBM), whose tumors have EGFR (epidermal growth factor receptor) amplification, demonstrated no survival benefit for patients receiving Depatux-M at an interim analysis (Press release, AbbVie, MAY 17, 2019, View Source [SID1234536457]). An Independent Data Monitoring Committee (IDMC) recommended the study be stopped due to lack of survival benefit for patients receiving Depatux-M compared with placebo when added to the standard regimen of radiation and temozolomide. No new safety findings were observed. Enrollment in all ongoing Depatux-M studies has been halted.

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"Glioblastoma patients and their caregivers face a devastating disease for which there are few therapeutic options. While we are disappointed that Depatux-M did not demonstrate a survival benefit in the INTELLANCE-1 study, we remain committed to discovering and developing therapies to address some of the most debilitating cancers," said Michael Severino, M.D., vice chairman and president, AbbVie.

The INTELLANCE-1 trial was conducted in collaboration with the RTOG Foundation, an independent, non-profit cancer research organization. Results from INTELLANCE-1 will be submitted for presentation at a medical conference and for publication in a peer-reviewed journal.

"The highly collaborative partnership between RTOG Foundation’s scientific and physician leaders, under the leadership of Andrew Lassman, M.D., the study principal investigator, and the AbbVie team facilitated the early completion of this important international clinical trial. The RTOG Foundation’s outstanding glioblastoma experts will continue to vigorously investigate new approaches to this very challenging malignancy," said Walter J. Curran Jr., M.D., F.A.C.R., F.A.S.C.O., RTOG Foundation Board Chair and Executive Director of the Winship Cancer Institute of Emory University.

About the Phase 3 INTELLANCE-1 Trial and Depatuxizumab Mafodotin (Depatux-M; ABT-414)
The randomized, placebo-controlled Phase 3 study was designed to evaluate the efficacy and safety of Depatux-M versus placebo when administered with concurrent radiation and temozolomide and with adjuvant temozolomide in subjects with newly diagnosed EGFR-amplified GBM.1 The primary endpoint was overall survival, and the interim analysis was based on data from 639 patients. Depatux-M is not approved, and its safety and efficacy have not been evaluated by regulatory authorities.

About AbbVie in Oncology
At AbbVie, we strive to discover and develop medicines that deliver transformational improvements in cancer treatment by uniquely combining our deep knowledge in core areas of biology with cutting-edge technologies, and by working together with our partners – scientists, clinical experts, industry peers, advocates, and patients. We remain focused on delivering these transformative advances in treatment across some of the most debilitating and widespread cancers. We are also committed to exploring solutions to help patients obtain access to our cancer medicines. With the acquisitions of Pharmacyclics in 2015 and Stemcentrx in 2016, our research and development efforts, and through collaborations, AbbVie’s oncology portfolio now consists of marketed medicines and a pipeline containing multiple new molecules being evaluated worldwide in more than 300 clinical trials and more than 20 different tumor types. For more information, please visit View Source

On May 17, 2019 Ligand Pharmaceuticals Incorporated (NASDAQ: LGND) reported the signing of a license agreement granting Cumulus Oncology exclusive worldwide rights to develop and commercialize VER250840, a novel, oral, selective, preclinical Chk1 Kinase Inhibitor discovered using Ligand’s Vernalis Design Platform (VDP) (Press release, Ligand, MAY 17, 2019, View Source [SID1234536461]). Under the terms of the agreement, Ligand will receive an upfront license fee, and is eligible to receive over $76 million of milestone payments and tiered royalties in the mid-to-high single digit range, depending on revenue. In addition, Ligand is eligible to receive an additional fee, payable in cash or Cumulus equity, upon Cumulus achieving specified financing-related events.

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"We are pleased to be partnered with Cumulus to continue to advance the development of this important kinase target," said John Higgins, Chief Executive Officer of Ligand. "Since Ligand’s acquisition of Vernalis in October of last year, the business in Cambridge has been successfully integrated and is significantly contributing to the advancement of Ligand’s Shots-on-Goal business model. VDP consists of a team of accomplished scientists servicing the needs of partners to design molecules addressing highly-challenging targets, and we expect additional partnered programs to result from their efforts over the coming months and years."

About VER250840

VER250840 is a novel oral, selective Chk1 kinase inhibitor discovered using the Vernalis Design Platform (VDP). Chk1 is an important target within the DNA Damage Response (DDR) network and has been shown to play a key role in maintaining genomic integrity of cancer cells. Inhibition of Chk1 blocks cell cycle arrest and DNA repair, forcing cancer cells to undergo cell division with substantial DNA damage that results in their death. In both in vitro and in vivo preclinical studies, VER250840 has demonstrated an ability to target Chk1 in a range of different tumor types, as a single agent and in combination with several different cytotoxic agents. The clinical utility of DDR inhibitors for the treatment of cancer has recently been validated by the approval of inhibitors of Poly (ADP-ribose) polymerase (PARP). The opportunity to select patients most likely to respond to Chk1 inhibitors exists.

About the Vernalis Design Platform (VDP)

Vernalis (R&D) Limited is a Ligand subsidiary based in Cambridge, UK, and is a world leader in structure-guided drug discovery. The Vernalis Design Platform (VDP) integrates protein structure determination and engineering, fragment screening and molecular modeling, with medicinal chemistry, to enable success in novel drug discovery programs against highly-challenging targets. A key element to the success of VDP is establishing a robust platform for drug discovery for each target to validate hit identification using multiple proprietary assay and biophysical systems. Vernalis has collaborations across many therapeutic areas, including oncology, CNS, anti-infectives and inflammation, with global partners and a heritage of successful internal drug discovery in oncology and anti-infectives.