On October 17, 2019 Xcovery Holdings, Inc., an oncology-focused biopharmaceutical company, reported that ensartinib, the company’s lead drug candidate, demonstrated efficacy and safety in patients with crizotinib-refractory, anaplastic lymphoma kinase (ALK) positive non-small cell lung cancer (NSCLC), including those with brain metastases (Press release, Xcovery, OCT 17, 2019, View Source [SID1234542341]). The peer-reviewed manuscript of the study, "Efficacy, safety, and biomarker analysis of ensartinib in crizotinib-resistant, ALK-positive non-small-cell lung cancer: a multicentre, phase 2 trial" was published online in The Lancet Respiratory Medicine.

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"These results from the ensartinib China registration trial are very encouraging. They support our ongoing global phase 3 efforts in evaluating ensartinib’s efficacy and safety in the first line setting," said Li Mao, M.D., Chief Executive Officer of Xcovery, "Our company is dedicated to developing drugs to help cancer patients and we believe ensartinib has the potential to be the best-in-class first line therapy for ALK-positive NSCLC patients."

The multicenter phase 2 registration study analyzed the efficacy and safety of ensartinib in ALK-positive NSCLC patients that failed prior crizotinib treatment. The study also explored the associations between ensartinib efficacy and crizotinib-resistant mutations.

Ensartinib showed very promising activity in patients with ALK-positive NSCLC whose disease had progressed on previous crizotinib therapy. 52% (95% CI 43–60) of patients had a systemic objective response, whereas 70% (53–83) had an intracranial objective response, as assessed by an independent review committee.

In the study, most treatment-related adverse events were grade 1 or 2 and low proportions of patients required dose modifications or discontinued. Ensartinib also demonstrated activity against a broad array of ALK mutations, including G1202R, G1269A, F1174, C1156Y, and T1151.

D. Ross Camidge, M.D., from the University Of Colorado Department Of Medicine provided the Editorial Comment for the Lancet published study. "The median progression-free survival associated with ensartinib (9.6 months) was remarkably similar to that reported for the same drug at the same dose in a separate US study (9.2 months)," noted Dr. Camidge. "Cross-trial comparison would suggest that ensartinib’s activity is thus likely to be similar, if not marginally superior, to that of alectinib."

"This data set supports ensartinib as a new option for ALK-positive NSCLC patients in a refractory setting," said Giovanni Selvaggi, M.D., Chief Medical Officer at Xcovery and co-author of the study. "The high efficacy against brain metastases and the encouraging signal in resistant mutations, including G1202R, make ensartinib a promising treatment in an area where there is still significant unmet medical need."

To view the article, please visit https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(19)30252-8/fulltext.

For more information on the ensartinib phase 3 clinical trial, please visit clinicaltrials.gov.

About Ensartinib

Ensartinib (X-396) is a potent anaplastic lymphoma kinase (ALK) inhibitor currently in a global phase 3 trial for ALK-positive NSCLC in the first line.

On October 17, 2019 Immunomic Therapeutics, Inc. reported a presentation at the Precision Lung Cancer World R&D Summit in Boston (Press release, Immunomic Therapeutics, OCT 17, 2019, View Source [SID1234542340]). On Tuesday, October 22, Business Development Advisor at Immunomic, Yan Su, will present a talk entitled "Current & Future Application of the UNITE Platform in Cancer Immunotherapy," highlighting Immunomic’s investigational UNiversal Intracellular Targeted Expression (UNITE) platform and its application in immuno-oncology.

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Immunomic’s UNITE technology platform has the potential to utilize the body’s natural biochemistry to develop a broad immune response, including antibody production, cytokine release and critical immunological memory, a method that could put UNITE at the crossroads of immunotherapies in a number of illnesses, including cancer. The investigational UNITE technology is currently being applied as a cancer immunotherapy in a Phase II clinical trial targeting glioblastoma multiforme (GBM). Su’s presentation will explore the broader potential of UNITE through discussion of the LAMP-based immunotherapy technology, VAC2. VAC2 is an allogeneic cancer immunotherapy being developed by Lineage Cell Therapeutics, Inc. in collaboration with Cancer Research UK and is currently in a Phase 1 clinical trial for treatment of non-small cell lung cancer. In addition, the presentation will discuss the potential application of the UNITE Platform in Cancer targeting shared neoantigens.

Who: Yan Su, Business Development Advisor at Immunomic Therapeutics, Inc.

What: Presentation on Current & Future Application of the UNITE Platform in Cancer Immunotherapy

When: Tuesday, October 22 at 4:00 p.m. ET

Where: Wyndham Boston Beacon Hill, 5 Blossom St., Boston, MA 02114

About UNITE

ITI’s investigational UNITE platform, or UNiversal Intracellular Targeted Expression, works by fusing pathogenic antigens with the Lysosomal Associated Membrane Protein, an endogenous protein in humans, for immune processing and MHC-II presentation to helper T-cells. In this way, ITI’s vaccines (DNA or RNA) have the potential to utilize the body’s natural biochemistry to develop a broad immune response including antibody production, cytokine release and critical immunological memory. This approach could put UNITE technology at the crossroads of immunotherapies in a number of illnesses, including cancer, allergy and infectious diseases. UNITE is currently being employed in Phase II clinical trials as a cancer immunotherapy. ITI is also collaborating with academic centers and biotechnology companies to study the use of UNITE in cancer types of high mortality, including cases where there are limited treatment options like glioblastoma and acute myeloid leukemia. ITI believes that these early clinical studies may provide a proof of concept for UNITE therapy in cancer, and if successful, set the stage for future studies, including combinations in these tumor types and others. Preclinical data is currently being developed to explore whether LAMP nucleic acid constructs may amplify and activate the immune response in highly immunogenic tumor types and be used to create immune responses to tumor types that otherwise do not provoke an immune response.

On October 17, 2019 Selexis SA and Teneobio, Inc. reported that they have signed three commercial license agreements (CLAs) for the development of Teneobio’s Human Heavy-Chain Antibodies (UniAbs), a new class of multi-specific biologics, for the treatment of multiple myeloma, lymphoma and prostate cancer (Press release, TeneoBio, OCT 17, 2019, View Source [SID1234542339]). The CLAs expand the companies’ previously established relationship, including a service agreement signed between Teneobio and Selexis in December 2018.

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Through each new CLA, Selexis will provide Teneobio with access to high performance research cell banks (RCBs) developed using the Selexis SUREtechnology Platform, with each expressing a unique UniAb product candidate.

"Today, new generations of biologically engineered antibody therapies are reaching the clinic with Selexis technologies that are specifically engineered to address the challenges of achieving high expression levels for and quality thresholds of bi- and multi-specific antibodies. Teneobio’s multi-specific UniAbs represent an exciting opportunity to leverage our capabilities," said Yemi Onakunle, PhD, MBA, Selexis senior vice president, licensing and business development. "We’re pleased that the SUREtechnology Platform has positively impacted the trajectory of Teneobio’s pipeline and we look forward to working with their team to bring these exciting new oncology biologics to the clinic."

Bi- and multi-specific antibodies represent one of the fastest-growing classes of molecules offering new therapeutic perspectives. A bi/multi-specific antibody is a recombinant, engineered protein that can simultaneously bind to two or more different types of antigens, often on two or more different types of cells. For cancer therapies, one-half of a bispecific recognizes an antigen on an immune cell, typically a T-cell, and the other half recognizes an antigen on the tumor. By binding both antigens simultaneously, a bispecific brings T-cells in close proximity to tumor cells where they can kill them.

"Since we began working with Selexis two years ago, we’ve seen firsthand the benefits of its cell line expression technologies – high-yield, speed, stability, flexibility and applicability for use with our differentiated, multi-specific platform – all of which are essential for bringing our innovative UniAbs to patients," said Omid Vafa, PhD, MBA, chief business officer at Teneobio, Inc. "We look forward to continuing our important work together."

Selexis’ modular SUREtechnology Platform facilitates the rapid, stable, and cost-effective production of virtually any recombinant protein and provides seamless integration of the biologics development continuum, spanning discovery to commercialization.

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.