On October 17, 2019 Plexium reported the launch of the company with the closing of a $28 million Series A financing (Press release, Plexium, OCT 17, 2019, View Source [SID1234542338]). The financing was led by DCVC Bio and The Column Group, with participation from M Ventures, CRV, and Neotribe Ventures. The company’s proprietary platform, DELPhe, enables cell-based phenotypic screening of DNA-encoded libraries in nanoliter volumes.

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Proceeds from the financing will be used to further advance Plexium’s DELPhe platform and build a pipeline of small molecules that modulate E3 ligases to selectively enhance and degrade protein targets. Disease-specific profiles of desired protein modulation are informed by human clinical and translational biomarker observations. By screening millions of small molecules, simultaneously, for their impact on cellular RNA and protein levels, compounds with the desired activity profiles will be selected and advanced as therapeutic candidates in oncology and neurodegenerative diseases.

"Inducing protein degradation by redirecting E3 ligases is an exciting therapeutic modality with immense potential to create safe and effective new medicines," said Kandaswamy (Swamy) Vijayan, Ph.D., founder and CEO of Plexium. "The levels of a vast majority of proteins in the cell are modulated by E3 ligases, including disease targets considered ‘undruggable.’ DELPhe can efficiently identify therapeutic small molecules for the precise manipulation of E3 ligases, unlocking control of disease-modifying pathways."

Plexium’s strategy employing the DELPhe platform is unlike other approaches to targeted protein degradation. While other strategies require a small molecule known to bind a protein target to be degraded, the DELPhe platform utilizes target-specific degradation assays and phenotypic screens to find small molecules that reduce levels of the target protein in cells. This creates an opportunity to identify small molecules to undruggable protein targets through screening approaches that do not require prior knowledge of molecules that bind the target.

In conjunction with the financing, Kiersten Stead, Ph.D., managing partner of DCVC Bio, and Tim Kutzkey, Ph.D., managing partner of The Column Group, have joined Plexium’s board of directors.

"Plexium is replacing the complex infrastructure around drug discovery with an ultra-high-throughput microfluidic platform while reducing assay complexity and supercharging chemical diversity," said Kiersten Stead. "The richness and scale of data that can be generated from the DELPhe platform are poised to transform drug development. We are thrilled to support Plexium in its mission to develop the ultimate tool for drugging undruggable proteins."

"Plexium is an interesting amalgam of cutting-edge engineering coupled with the latest advances in chemistry and biology," said Tim Kutzkey. "We are impressed with the vision of the DELPhe platform and its applicability to E3 ligase modulation. We believe tuning E3 ligases opens up immense opportunities for first-in-class therapeutics, and we are excited to be supporting the novel approaches and therapeutic opportunities being pursued at Plexium."

Plexium will be presenting at the Targeted Protein Degradation Summit in Boston on October 23.

On October 17, 2019 Mirati Therapeutics, Inc. (NASDAQ: MRTX), a clinical-stage targeted oncology company, reported it will present pre-clinical data and initial clinical data on MRTX849, a novel and optimized KRAS G12C inhibitor, in presentations at the AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) in Boston, October 26-30, 2019 at the Hynes Convention Center (Press release, Mirati, OCT 17, 2019, View Source [SID1234542337]).

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On Monday, October 28, beginning at 4:20pm EDT, pre-clinical MRTX849 data will be presented in an oral presentation, "The KRAS G12C Inhibitor, MRTX849, Provides Insight Toward Therapeutic Susceptibility of KRAS Mutant Cancers" during "Concurrent Session 5: Targeting the RAS/MAP Kinase Pathway" by Dr. James Christensen, Ph.D., Executive Vice President and Chief Scientific Officer at Mirati. Following the pre-clinical presentation, MRTX849-001 Investigator, Dr. Pasi A. Janne, M.D., Ph.D., Director of the Lowe Center for Thoracic Oncology at Dana-Farber Cancer Institute, Professor of Medicine, Harvard University and the Scientific Director of the Belfer Center for Applied Cancer Science will highlight initial clinical data for MRTX849 in an oral presentation, "A Phase 1 Clinical Trial Evaluating the Pharmacokinetics (PK), Safety, and Clinical Activity of MRTX849, a Mutant-Selective Small Molecule KRAS G12C Inhibitor, in Advanced Solid Tumors".

POSTER PRESENTATIONS

Additionally, MRTX849 pre-clinical data will be presented in two poster presentations.

Poster Title: Discovery and Pre-Clinical Development of MRTX849: A Mutation-Selective KRAS G12C Inhibitor
Session Title: Therapeutic Agents: Other
Session Date: Tuesday, October 29, 2019
Session Start Time: 12:30pm EDT
Session End Time: 4:00pm EDT
Location: Hall D, Hynes Convention Center
Abstract/Poster Number: C069

Poster Title: The KRAS G12C inhibitor MRTX849 reconditions the tumor immune microenvironment and leads to durable complete responses in combination with anti-PD-1 therapy in a syngeneic mouse model
Session Title: Late-Breaking Poster Session C: Therapeutic Agents: Other
Session Date: Tuesday, October 29, 2019
Session Start Time: 12:30pm EDT
Session End Time: 4:00pm EDT
Location: Hall D, Hynes Convention Center
Board Number: 156
Abstract/Poster Number: LB-C09

About MRTX849

MRTX849 is an investigational, orally-available small molecule that is designed to potently and selectively inhibit a form of KRAS which harbors a substitution mutation (G12C). KRAS G12C mutations are present in approximately 14% of NSCLC adenocarcinoma patients, 4% of colorectal cancer patients, and subsets of other types of cancer. Tumors characterized by KRAS G12C mutations are commonly associated with poor prognosis and resistance to therapy, and patients with these mutations have few treatment options. MRTX849 is being evaluated in a Phase 1/2 trial treating patients with molecularly-identified, KRAS G12C-positive advanced solid tumors.

On October 17, 2019 Verastem, Inc. (Nasdaq:VSTM) (Verastem Oncology or the Company), a biopharmaceutical company focused on developing and commercializing medicines seeking to improve the survival and quality of life of cancer patients, reported that the Company will host a conference call and webcast on Tuesday, October 29, 2019 at 4:30 p.m. Eastern Time to discuss corporate updates and financial results for the third quarter ended September 30, 2019 (Press release, Verastem, OCT 17, 2019, View Source [SID1234542336]).

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The call can be accessed by dialing (877) 341-5660 (U.S. and Canada) or (315) 625-3226 (international), five minutes prior to the start of the call and providing the passcode 5785818. The live, listen-only webcast of the conference call can be accessed by visiting the investors section of the Company’s website at www.verastem.com. A replay of the webcast will be archived on the Company’s website for 90 days following the call.

On October 17, 2019 Allergan plc (NYSE: AGN) reported it will release third quarter 2019 financial results on Tuesday, November 5, 2019, prior to the open of U.S. financial markets (Press release, Allergan, OCT 17, 2019, View Source [SID1234542335]).

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Allergan plc logo

For additional materials related to Allergan’s third quarter results, please visit Allergan’s Investor Relations website at View Source

On October 17, 2019 Syros Pharmaceuticals (NASDAQ:SYRS), a leader in the development of medicines that control the expression of genes, reported an update on its portfolio of selective cyclin-dependent kinase 7 (CDK7) inhibitors (Press release, Syros Pharmaceuticals, OCT 17, 2019, View Source [SID1234542333]). The Company has decided to prioritize the development of its highly selective and potent oral CDK7 inhibitor, SY-5609, and to discontinue further development of SY-1365, its intravenous (IV) CDK7 inhibitor. Syros expects to initiate a Phase 1 clinical trial of SY-5609 in patients with select solid tumors in the first quarter of 2020.

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SY-5609 inhibits CDK7 more selectively and potently than SY-1365 and has demonstrated greater anti-tumor activity than SY-1365 in multiple preclinical models. Furthermore, initial clinical activity and tolerability data from the expansion of the Phase 1 trial of SY-1365 did not support an optimal profile for patients, particularly in light of an increasing focus on oral targeted agents in cancer. As an oral molecule, Syros believes SY-5609 provides more flexibility in dosing and greater opportunity to sustain the levels of target coverage needed to improve treatment outcomes. Based on these factors, Syros has made a CDK7 portfolio decision to focus on SY-5609.

"We believe in selective CDK7 inhibition as a potentially transformative targeted approach for difficult-to-treat cancers," said Nancy Simonian, M.D., Chief Executive Officer of Syros. "SY-1365 was the first selective CDK7 inhibitor to enter clinical development, demonstrating proof-of-mechanism for this novel therapeutic approach and showing early signs of clinical activity. We have gained important insights from our work on SY-1365 that have informed our development strategy for SY-5609, including focusing on patient populations most likely to respond to a CDK7 inhibitor. We are prioritizing SY-5609 because we believe it has best-in-class potential and that it provides the greatest opportunity to realize the promise of selective CDK7 inhibition for patients."

SY-5609: An Oral, Highly Selective and Potent Non-Covalent CDK7 Inhibitor

SY-5609 has induced deep and sustained tumor growth inhibition, including complete regressions, in preclinical models of breast, ovarian and lung cancers at doses below the maximum tolerated dose. SY-5609 has also shown substantial anti-tumor activity in combination with fulvestrant in hormone receptor (HR)-positive breast cancer models that are resistant to CDK4/6 inhibitors. Importantly, SY-5609 showed greater tumor growth inhibition than SY-1365 in preclinical models in which they were both studied, including those that were not responsive to SY-1365.

Syros is on track to complete investigational new drug application-enabling studies for SY-5609 by year-end. The Company expects to initiate a Phase 1 trial in patients with select solid tumors, including breast, lung and ovarian cancers and cancers of any histology defined by a specific molecular signature, in the first quarter of 2020. Syros plans to present new preclinical data on the pharmacokinetics, pharmacodynamics and anti-tumor activity of SY-5609 on October 29 at the AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) in Boston. The abstract for the presentation is available on the conference website at: View Source

Initial data from expansion portion of Phase 1 trial of SY-1365

As of a planned September 30 data snapshot, 68 patients had been treated in the expansion portion of the Phase 1 trial of SY-1365, including 53 across the single-agent cohorts in patients with high-grade serous ovarian cancer (HGSOC), relapsed clear cell ovarian cancer and solid tumors of any histology available for biopsy, and 15 patients in the combination cohorts in HGSOC and metastatic CDK4/6 inhibitor-resistant HR-positive breast cancer.

Syros initiated the single-agent expansion cohorts at a dose of 80 mg/m2 twice weekly and the combination cohorts at 53 mg/m2 once weekly. During the expansion, peri-infusional adverse events (AEs) thought to be related to the IV administration of SY-1365 prompted evaluations of lower doses in the single-agent cohorts and extended infusion times across all the cohorts. Extended infusion times reduced peak drug concentrations and appeared to reduce the overall frequency and severity of peri-infusional AEs, including headache, nausea and vomiting.

The best response observed across the expansion cohorts was stable disease, as defined by RECIST criteria. Response-evaluable patients were primarily treated at doses of 53 and 64 mg/m2. Of the 31 response-evaluable patients treated with single-agent SY-1365, 13 (42 percent) had stable disease. Of the 11 response-evaluable patients treated in the combination cohorts, seven (64 percent) had stable disease.

Based on preclinical and clinical data, Syros believes that sustaining the level of CDK7 target coverage needed to enhance clinical activity would require more frequent dosing, or a higher dose that would necessitate further lengthening the infusion to manage tolerability. Syros believes that either approach could create an overly burdensome dosing schedule for patients that can better be addressed with SY-5609.

Conference Call and Webcast:

Syros will host a conference call at 8:30 a.m. ET today to discuss this update on its CDK7 franchise and plans to prioritize the development of SY-5609.

To access the live call, please dial 866-595-4538 (domestic) or 636-812-6496 (international) and refer to conference ID 4578949. A webcast of the call will also be available on the Investors & Media section of the Syros website at www.syros.com. An archived replay will be available for approximately 30 days following the call.