Sorrento Publishes an Abivertinib Teaser Entitled “Abivertinib – a Franchise Oral Therapeutic For Cancer, Covid-19 And Autoimmune Diseases

On November 29, 2021 Sorrento Therapeutics, Inc. (Nasdaq: SRNE, "Sorrento") reported the publication of a Teaser titled "Abivertinib – a Franchise Oral Therapeutic for Cancer, COVID-19 and Autoimmune Diseases" ("Abivertinib Teaser"). Sorrento intends to use the Abivertinib Teaser to engage in discussions with interested third parties in the pharmaceutical industry (Press release, Sorrento Therapeutics, NOV 29, 2021, View Source [SID1234596192]).

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The key highlights of the Abivertinib Teaser are outlined below:

Abivertinib for COVID-19 (Two Phase 2 trials Completed)
100 mg once-a-day oral capsule for hospitalized COVID-19 patients
US trial (N=96) and Brazil trial (N=400)
For Severe Ordinal Scale (OS) Category 5 COVID-19 Patients ("At-Risk Group") identified to be beneficial with Abivertinib treatment at Day 28 (D28):

Abivertinib reduced the risk of death or respiratory failure:

by 48% in US trial (death or respiratory failure: 21.7% in the Abivertinib group vs. 41.7% in the placebo plus Standard of Care (SoC) control group)
by 45% in Brazil trial (death or respiratory failure: 30.4% Abivertinib vs. 55.6% placebo plus SoC controls)

Abivertinib reduced the ICU stay:

by 2 days in the US trial (8.6 days average stay in ICU in Abivertinib group vs. 10.6 days in placebo plus SoC control group)

Abivertinib for Cancer Indications
NSCLC (Pivotal Trial: N=229) – Among 209 response evaluable NSCLC patients who developed resistance to first line Tyrosine Kinase Inhibitors (TKIs):

93.3% (n/N: 195/209) subjects achieved tumor shrinkage at target lesions
57.4% (n/N: 120/209) subjects achieved the best ORR (confirmed + unconfirmed
PR)
52.2% (n/N: 109/209) subjects achieved confirmed PR1
24.9 months OS
B-Cell Lymphoma (Phase 1/2 Trial) (as of 08/28/2020)

63.6% ORR (n/N: 14/22)
95.5% DCR (n/N: 21/22)
19.7 Months PFS
Abivertinib – A Broad Pipeline for Cancer, COVID-19 and Autoimmune Diseases ($61B Market)

Cancer Patients May Get Faster and More Personalized Treatment as Result of Collaboration Between GE Healthcare, University of Cambridge and Addenbrooke’s Hospital

On November 29, 2021 GE Healthcare, the University of Cambridge and Cambridge University Hospitals reported that they have agreed to collaborate on developing an application aiming to improve cancer care, with Cambridge providing clinical expertise and data to support GE Healthcare’s development and evaluation of an AI-enhanced application that integrates cancer patient data from multiple sources into a single interface (Press release, GE Healthcare, NOV 29, 2021, View Source [SID1234596211]).

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Building on research supported by The Mark Foundation for Cancer Research and Cancer Research UK, the collaboration aims to address the problems of fragmented or siloed data and disconnected patient information, which is challenging for clinicians to manage effectively and can prevent cancer patients receiving optimal treatment.

"Thanks to ever-improving technologies, we now generate increasing amounts of complex data for each patient with cancer. These include multiple imaging scans, digital pathology, genomic data, advanced blood tests and treatment information. Bringing all this data together to make precise and informed decisions for patients can be hard. We often do this inefficiently and miss important connections between the data," said Professor Richard Gilbertson, Director of the Cancer Research UK Cambridge Centre, and Head of the Department of Oncology at the University of Cambridge.

This new application would be designed using advanced software engineering and machine learning methods to integrate a variety of patient data including clinical, imaging and genomic data – from diagnosis through every stage of treatment – into one single location. The aim is to offer all medical teams involved in a patient’s cancer care – medical oncologists, clinical oncologists, surgeons, radiologists, pathologists, clinical nurse specialists and more – simultaneous access to the necessary data and information to allow the medical team to plan the best, most personalized treatment for each of their patients.

The application is expected to be evaluated for ovarian cancer initially in Cambridge and the goal is to evaluate it across the UK, and beyond. Ovarian cancer is often difficult to treat as most patients present with advanced disease. Although initially 70-80% of patients will respond well to chemotherapy, ultimately most develop chemotherapy resistance leading to treatment failure.1 The application may help clinicians have better visibility on how the patient respond to treatment, thus helping them more effectively identify when treatment may require adjustment. If the application is successfully developed, our vision is for it to be expanded for use in breast and kidney cancer patients.

"Healthcare professionals can struggle to easily find and interpret the many different types of patient data information they need to make the best clinical decisions," said Dr Ben Newton, GM Oncology at GE Healthcare. "Bringing these multiple data streams into a single interface could enable clinicians to make fast, informed and highly personalised treatment decisions throughout a patient’s cancer care pathway."

Two Addenbrooke’s cancer clinicians aiming to evaluate the application to help patients are consultant oncologist Prof. James Brenton, professor of Ovarian Cancer Medicine and a senior group leader at the Cancer Research UK Cambridge Institute; and consultant radiologist Prof. Evis Sala, professor of Oncological Imaging, University of Cambridge.

"Aggregating and analysing the substantial amounts of data available would help address an unmet need. Ovarian cancer is an important and complex disease with poor outcomes, and we believe this application would help us deal with its complexity. Eventually, we hope to be able to better understand the disease and therefore improve treatment and outcomes for patients," says Prof. Brenton, who co-leads the Mark Foundation Institute for Integrated Cancer Medicine (MFICM) at the University of Cambridge.

"If we can aggregate and integrate relevant data along the care pathway, and visualize the output, it may ultimately lead to clinicians making better-informed decisions and better care." adds Prof. Sala who also co-leads the MFICM at the University of Cambridge.

"The team aims to transform the delivery of cancer patient care by integrating multiple data streams together into a single platform that can be accessed simultaneously by clinicians, patients and multi-disciplinary teams (MDTs) from tertiary and regional hospitals."

The development work will be underpinned by GE Healthcare’s Edison platform to integrate data from diverse sources, such as electronic health records (EHR) and radiology information systems (RIS), imaging and other medical device data.

Kineta Presents Phase 1/2 Clinical Trial Design of KVA12.1 at the Society for Immunotherapy of Cancer (SITC) 36th Annual Meeting

On November 29, 2021 Kineta, Inc., a clinical stage biotechnology company focused on the development of novel immunotherapies in oncology, reported a presentation describing the Phase 1/2 trial design supporting KVA12.1 for the potential treatment of difficult-to-treat solid tumors at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 36th Anniversary Annual Meeting (Press release, Kineta, NOV 29, 2021, View Source;utm_medium=rss&utm_campaign=kineta-presents-clinical-trial-design-of-kva12-at-sitc [SID1234596193]). Thierry Guillaudeux, PhD, Senior Vice President Immuno-oncology at Kineta, presented a poster outlining the first-in-human clinical trial design KVA 12.1, a novel fully human anti-VISTA antibody, in monotherapy and in combination with an anti-PD1 antibody.

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"Our fully human anti-VISTA antibody, KVA12.1, which binds to a unique epitope has been optimized to reduce the potential risks of severe inflammation . It demonstrates excellent clinical characteristics including an extended pharmacokinetic (PK) profile" said Thierry Guillaudeux, PhD, Senior Vice President Immuno-oncology at Kineta. "We are encouraged by the exceptional preclinical results of KVA12.1 and are eager to enter the clinic with KVA12.1 in the third quarter of 2022."

The Phase 1/2 study will be a multicenter, open label, dose escalation and dose expansion study of intravenous infusion of KVA12.1 as a monotherapy and in combination with a fixed dose of an anti-PD1 antibody in patients with advanced refractory or metastatic solid tumors.

Study objectives detailed from the SITC (Free SITC Whitepaper) poster presentation:

Primary objective: Evaluate the safety, tolerability, Dose Limiting Toxicity (DLT), Maximum Tolerated Dose (MTD) and Identify the Recommended Phase 2 Dose (RP2D) of VISTA-Mab when administered alone and in combination with an anti-PD1 antibody.
Secondary objectives: Further describe i) the PK of KVA12.1; ii) VISTA-Receptor Occupancy; and iii) the anti-tumor activity of KVA12.1 (alone and in combination).
Presentation Details:

Title: KVA 12.1 a novel fully human anti-VISTA antibody clinical trial design in monotherapy and in combination with an anti-PD1 antibody

Date Presented: November 12-13, 2021
Presenter: Thierry Guillaudeux, PhD

Poster: Click on the link below to view the poster:

VISTA Publications – Poster Presentation at SITC (Free SITC Whitepaper) 2021

KVA12.1 is a fully human, optimized IgG1 monoclonal antibody (mAb) that was designed to bind to VISTA through a unique epitope. KVA12.1 drives strong antitumor immune cell activation:

Increases inflammatory monocyte differentiation and activation
Increases HLA-dependent T cell activation
Reduces MDSC-mediated T cell suppression
In preclinical models, KVA12.1 demonstrates strong single agent efficacy in poorly immunogenic "cold tumors" and complementary efficacy when dosed in combination with immune checkpoint inhibitors (ICIs) like PD-1 or CTLA-4. It is well-tolerated with no change in IL6 or TNFα levels, which are responsible for cytokine release syndrome (CRS), in toxicology studies. KVA12.1 is being developed as an intravenous infusion.

KVA12.1 may be an effective immunotherapy for many types of cancer patients including non-small cell lung cancer (NSCLC), colorectal (CRC), renal cell carcinoma (RCC), head and neck squamous cell carcinoma (HNSCC), and ovarian (OC) cancers.

Ranok Therapeutics Announces Agreement with Pfizer on Targeted Protein Degradation

On November 29, 2021 Ranok Therapeutics (Hangzhou) Co. Ltd., an emerging biopharmaceutical company focused on developing breakthrough therapies for cancer and other serious diseases, reported an agreement with Pfizer Inc. to apply and evaluate Ranok’s CHAMP platform technology on an undisclosed cancer target (Press release, Ranok Therapeutics, NOV 29, 2021, View Source [SID1234596212]). Terms of the agreement were not disclosed.

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Ranok has developed a proprietary and innovative targeted protein degradation (TPD) platform technology, CHAMP (Chaperone-mediated Protein Degradation), which leverages Ranok’s founders’ expertise in protein homeostasis to take advantage of the cellular chaperone network, potentially improving drug safety and efficacy due to selective targeting of disease tissues.

"We are very pleased to work with Pfizer to explore the application of CHAMP to an emerging cancer drug target," said Kevin P. Foley, Ph.D., Co-founder and Chief Scientific Officer of Ranok Therapeutics. "This represents our first pharmaceutical company research relationship and is an important step forward in establishing CHAMP as a preferred technology in the rapidly-growing field of targeted protein degradation. We look forward to uncovering new benefits of CHAMP through this research."

This evaluation agreement builds upon Ranok’s recent momentum, including its $40 million Series B financing in August 2021.

Blueprint Medicines to Expand Precision Therapy Leadership in Lung Cancer with Acquisition of Lengo Therapeutics

On November 29, 2021 Blueprint Medicines Corporation (NASDAQ: BPMC) reported that the company has entered into a definitive agreement under which it will acquire Lengo Therapeutics, a privately held precision oncology company, for $250 million in cash plus up to $215 million in additional potential payments based on the achievement of certain regulatory approval and sales-based milestones (Press release, Bristol-Myers Squibb, NOV 29, 2021, View Source [SID1234596194]).

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The acquisition includes Lengo Therapeutics’ lead compound LNG-451, a potential best-in-class oral precision therapy in development for the treatment of non-small cell lung cancer (NSCLC) in patients with EGFR exon 20 insertion mutations. Preclinical data show LNG-451 potently inhibits all common EGFR exon 20 insertion variants with marked selectivity over wild-type EGFR and off-target kinases. In addition, LNG-451 is highly brain-penetrant and has demonstrated compelling activity in a preclinical intracranial disease model.

Based on these and other preclinical data, Lengo Therapeutics anticipates it will submit an investigational new drug (IND) application for LNG-451 to the U.S. Food and Drug Administration (FDA) in December 2021.

"Our acquisition of Lengo Therapeutics deepens our commitment to advancing precision oncology therapies and specifically expands our opportunity to transform treatment for patients with EGFR-driven lung cancer," said Jeff Albers, Chief Executive Officer of Blueprint Medicines. "The Lengo team has done tremendous work in designing a highly selective therapeutic candidate tailored to the needs of patients with EGFR exon 20 lung cancer, including features with the potential to enable treatment or prevention of brain metastases. With our integrated precision therapy research, development and commercial capabilities, Blueprint Medicines is perfectly positioned to carry forward this compound into the clinic and deliver on our goal to meaningfully advance care for NSCLC patients with EGFR exon 20 insertion mutations."

"With a proven track record of developing and delivering precision therapies for patients with significant medical needs and a compelling lung cancer portfolio, Blueprint Medicines is unique in its abilities to quickly progress LNG-451," said Enoch Kariuki, Chief Executive Officer of Lengo Therapeutics. "From our inception, the Lengo Therapeutics team has focused on generating best-in-class compound profiles, prioritizing those with brain penetration along with high potency and selectivity, like LNG-451. I am incredibly proud of the team for getting us to this point and excited to see the programs continue under Blueprint Medicines’ leadership."

With the addition of LNG-451, Blueprint Medicines will have three investigational compounds, each with best-in-class potential, that cover the majority of all activating mutations in EGFR, the second most common oncogenic driver in NSCLC.1 Approximately 12 percent of activating EGFR mutations are exon 20 insertions and significant medical need remains for patients harboring these mutations, including new treatment options with improved tolerability, combinability and enhanced brain penetration to treat or prevent brain metastases.1

The acquisition also brings additional undisclosed preclinical precision oncology programs and research tools, including a catalog of covalent, highly brain penetrant kinase inhibitors that Blueprint Medicines plans to add to its proprietary compound library to further enable future drug discovery efforts.

Blueprint Medicines anticipates the acquisition will close in the fourth quarter of 2021, subject to certain conditions, including the expiration of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act and other customary conditions.

Goldman Sachs & Co. LLC is acting as financial advisor to Blueprint Medicines and Goodwin Procter LLP is acting as its legal counsel. Centerview Partners LLC is acting as financial advisor to Lengo Therapeutics and Cooley LLP is acting as its legal counsel.

Conference Call Information

Blueprint Medicines will host a live webcast beginning at 8:30 a.m. ET today to discuss the planned acquisition of Lengo Therapeutics. To access the live call, please dial 844-200-6205 (domestic) or 929-526-1599 (international) and refer to conference ID 936793. A webcast of the conference call will be available under "Events and Presentations" in the Investors & Media section of Blueprint Medicines’ website at View Source The archived webcast will be available on Blueprint Medicines’ website approximately two hours after the conference call and will be available for 90 days following the call.

About Blueprint Medicines’ EGFR Development Program

Derived from Blueprint Medicines’ proprietary research platform, BLU-945 and BLU-701 are investigational next-generation EGFR non-covalent tyrosine kinase inhibitors. Both treatments are specifically designed to provide comprehensive coverage of the most common activating and on-target resistance mutations, spare wild-type EGFR and other kinases to limit off-target toxicities and enable a range of combination strategies, and treat or prevent central nervous system metastases. BLU-945 is currently being evaluated in the Phase 1/2 SYMPHONY trial in patients with previously treated EGFR-driven NSCLC (NCT04862780). In addition, Blueprint Medicines plans to initiate a Phase 1/2 trial of BLU-701 in the fourth quarter of 2021.