On April 28, 2021 BeiGene (NASDAQ: BGNE; HKEX: 06160) reported positive results from a planned interim analysis of the Phase 3 ALPINE trial comparing BRUKINSA (zanubrutinib) against ibrutinib in adults with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) (Press release, BeiGene, APR 28, 2021, View Source [SID1234578640]).

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BRUKINSA met the primary endpoint of the trial, demonstrating non-inferiority in objective response rate (ORR) by both investigator and independent review committee (IRC) assessments (p < 0.0001). The trial also demonstrated superior ORR with a statistically significant improvement in ORR for BRUKINSA vs. ibrutinib (p = 0.0006) by investigator assessment, as well as a numerically higher ORR but not statistically significant improvement by IRC (p = 0.0121 compared to the two-sided stringent statistical boundary of p < 0.0099 set for the interim analysis). The interim analysis from this fully-enrolled, ongoing trial is based on 415 of 652 patients followed for a minimum of 12 months.

Data pertaining to progression-free survival (PFS) in the 652 patients, a secondary endpoint of the trial, were immature at the data cutoff for the interim analysis. However, the descriptive summaries of PFS showed an early trend favoring BRUKINSA.

The trial also met a pre-specified secondary endpoint related to safety. Compared to ibrutinib, BRUKINSA demonstrated a statistically significant lower risk of atrial fibrillation or flutter, which is characterized by an irregular heartbeat that can lead to blood clots, stroke, heart failure and other heart-related complications. Overall, the safety profile of BRUKINSA was consistent with the previously seen profile in its clinical development program.

ALPINE is BeiGene’s second Phase 3 head-to-head trial comparing BRUKINSA to ibrutinib.

Jane Huang, M.D., Chief Medical Officer, Hematology of BeiGene said, "The interim results from this head-to-head trial demonstrated that, as a selective inhibitor designed to deliver sustained and continuous inhibition of BTK, BRUKINSA provides CLL patients with improvements in response and reduced rates of atrial fibrillation or flutter compared to ibrutinib. Data from this interim analysis, in addition to BRUKINSA’s comprehensive clinical program, provide important new information to support its benefit-risk profile."

BeiGene plans to consult with global regulatory authorities on next steps and present these data at an upcoming major medical conference. ORR per IRC will be further assessed at the planned final analysis, and patients will be followed for analyses on key secondary endpoints including PFS.

About Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma

Chronic lymphocytic leukemia (CLL) is the most common form of leukemia in adults, with a global incidence of approximately 114,000 new cases in 2017.1,2 CLL affects white blood cells or lymphocytes in the bone marrow.1 Proliferation of cancer cells (leukemia) in the marrow result in reduced ability to fight infection and spread into the blood, which affects other parts of the body including the lymph nodes, liver and spleen.1,3 The BTK pathway is a known route that signals malignant B cells and contributes to the onset of CLL.4 Small lymphocytic lymphoma (SLL) is a non-Hodgkin’s lymphoma affecting the B-lymphocytes of the immune system, which shares many similarities to CLL but with cancer cells found mostly in lymph nodes.5

About ALPINE

ALPINE is a randomized, global Phase 3 trial (NCT03734016) comparing BRUKINSA against ibrutinib in previously treated patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

In the trial, a total of 652 patients were randomized into two arms with the first receiving BRUKINSA (160 mg orally twice daily) and the second receiving ibrutinib (420 mg orally once daily) until disease progression or unacceptable toxicity. The primary analysis of objective response rate (ORR), defined by pre-specified non-inferiority of BRUKINSA versus ibrutinib, was assessed by investigator and independent review committee (IRC) using the modified 2008 iwCLL guidelines with modification for treatment-related lymphocytosis for patients with CLL and per Lugano Classification for non-Hodgkin’s lymphoma for patients with SLL. There was hierarchical testing of non-inferiority followed by superiority in ORR as assessed by investigator and IRC. Key secondary endpoints include progression-free survival (PFS), duration of response, overall survival, and incidence of adverse events. The study is ongoing, with pre-specified endpoints of ORR and PFS to be evaluated at the planned final analysis expected in 2022.

About BRUKINSA

BRUKINSA is a small molecule inhibitor of Bruton’s tyrosine kinase (BTK) discovered by BeiGene scientists that is currently being evaluated globally in a broad clinical program as a monotherapy and in combination with other therapies to treat various B-cell malignancies. Because new BTK is continuously synthesized, BRUKINSA was specifically designed to deliver complete and sustained inhibition of the BTK protein by optimizing bioavailability, half-life, and selectivity. With differentiated pharmacokinetics compared to approved BTK inhibitors, BRUKINSA has been demonstrated to inhibit the proliferation of malignant B cells within a number of disease relevant tissues.
BRUKINSA is approved in the following indications and regions:

•For the treatment of mantle cell lymphoma (MCL) in adult patients who have received at least one prior therapy (United States, November 2019)*;

•For the treatment of MCL in adult patients who have received at least one prior therapy (China, June 2020)**;

•For the treatment of chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) in adult patients who have received at least one prior therapy (China, June 2020)**;

•For the treatment of relapsed or refractory MCL (United Arab Emirates, February 2021); and

•For the treatment of Waldenström’s macroglobulinemia (WM) in adult patients (Canada, March 2021).

To-date, more than 30 marketing authorization applications in multiple indications have been submitted outside of the United States and China, covering the EU and more than 20 other countries.

*This indication was approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

**This indication was approved under conditional approval. Complete approval for this indication may be contingent upon results from ongoing randomized, controlled confirmatory clinical trials.

On April 28, 2021 Jounce Therapeutics, Inc. (NASDAQ: JNCE), a clinical-stage company focused on the discovery and development of novel cancer immunotherapies and predictive biomarkers, reported that two trial in progress posters, on the Phase 1 INNATE clinical trial and the Phase 2 SELECT clinical trial, will be presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Virtual Annual Meeting being held June 4-8, 2021 (Press release, Jounce Therapeutics, APR 28, 2021, View Source [SID1234578658]).

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Poster Details:

Poster Title: Phase 1, First-in-Human trial of JTX-8064, an anti-LILRB2/ILT4 monoclonal antibody, as monotherapy and in combination with anti-PD-1 in adult patients with advanced solid tumors (INNATE)
Presenter: Kyriakos P. Papadopoulos, MD, South Texas Accelerated Research Therapeutics (START), San Antonio, TX
Session Title: Developmental Therapeutics – Immunotherapy
Abstract Number: TPS2672
Date and Time: Friday, June 4, 2021; 9:00am ET

Poster Title: Phase 2 Study of PD-1 Inhibitor JTX-4014 (Pimivalimab) Alone and in Combination with Vopratelimab, an ICOS Agonist, in Biomarker-selected Subjects with Metastatic NSCLC After One Prior Platinum-containing Regimen (SELECT)
Presenter: Oleh Kobziev, MD, Regional Center of Oncology, Kharkiv, 61070, Ukraine
Session Title: Lung Cancer – Non-Small Cell Metastatic
Abstract Number: TPS9137
Date and Time: Friday, June 4, 2021; 9:00am ET

About JTX-8064

JTX-8064 is a humanized IgG4 monoclonal antibody designed to specifically bind to Leukocyte Immunoglobulin Like Receptor B2 (LILRB2/ILT4) and block interactions with its ligands. JTX-8064 is the first tumor-associated macrophage candidate developed from Jounce’s Translational Science Platform. Preclinical data presented at the 2020 Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s Annual Meeting and the 2019 and 2021 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meetings support the development of JTX-8064 as a novel immunotherapy to reprogram immune-suppressive macrophages and enhance anti-tumor immunity. A Phase 1 clinical trial named INNATE (NCT04669899), of JTX-8064 as a monotherapy and in combination with either Jounce’s internal anti-PD-1 inhibitor, pimivalimab (formerly JTX-4014), or an approved anti-PD-1 inhibitor, is currently enrolling patients with advanced solid tumors.

About Pimivalimab

Pimivalimab (formerly JTX-4014) is a well-characterized fully human IgG4 monoclonal antibody designed to block binding to PD-L1 and PD-L2. Pimivalimab demonstrated a 17% durable overall response rate in a Phase 1 trial of 18 heavily pre-treated PD-(L)1 inhibitor naïve patients, which excluded all tumor types for which PD-(L)1 inhibitors were approved. In this Phase 1 trial, pimivalimab was shown to have an acceptable safety profile. Pimivalimab is currently being assessed in the INNATE Phase 1 trial (NCT04669899) in combination with JTX-8064, a LILRB2 (ILT4) inhibitor. Pimivalimab is also being assessed in the SELECT Phase 2 clinical trial (NCT04549025) in combination with vopratelimab, a clinical-stage monoclonal antibody that binds to and activates ICOS, the Inducible T cell CO-Stimulator, a protein on the surface of certain T cells commonly found in many solid tumors. The SELECT trial compares vopratelimab plus pimivalimab to pimivalimab alone in immunotherapy naïve NSCLC patients who have been pre-selected with the TISvopra predictive biomarker, an 18 gene RNA tumor inflammation signature which predicted the emergence of ICOS hi CD4 T cells and clinical benefit in the ICONIC trial of vopratelimab alone and in combination with a PD-1 inhibitor.

About Vopratelimab

Vopratelimab is a clinical-stage monoclonal antibody that binds to and activates ICOS, the Inducible T cell CO-Stimulator, a protein on the surface of certain T cells commonly found in many solid tumors. Vopratelimab is currently being assessed in the SELECT Phase 2 clinical trial (NCT04549025) in combination with Jounce’s internal investigational PD-1 inhibitor, pimivalimab (formerly JTX-4014), compared to pimivalimab alone. The SELECT trial is currently enrolling approximately 75 immunotherapy naïve NSCLC patients who have been pre-selected with the TISvopra predictive biomarker, an 18 gene RNA tumor inflammation signature which predicted the emergence of ICOS hi CD4 T cells and clinical benefit in the ICONIC trial of vopratelimab alone and in combination with a PD-1 inhibitor. SELECT is powered to demonstrate the statistical superiority of the combination of vopratelimab plus pimivalimab compared to pimivalimab.

On April 28, 2021 Takeda Pharmaceutical Company Limited (TSE:4502/NYSE:TAK) ("Takeda") reported that it was awarded by the International Society for Pharmaceutical Engineering (ISPE) for the 2021 Facility Of the Year Awards (FOYA) in two categories (Press release, Takeda, APR 28, 2021, View Source [SID1234578683]). Takeda’s new solid pharmaceutical packaging building in Hikari, Japan, was recognized with the 2021 "Process Intelligence and Innovation" category award. Additionally, the end-to-end high potent drug facility in Grange Castle, Ireland, was selected as "Facility Integration" category winner.

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"I am honored that Takeda receives two awards for the production and packaging of small molecule solid dosage form products," said Thomas Wozniewski, global manufacturing & supply officer of Takeda. "In 2018, the Los Angeles plasma facility received two FOYA awards, now, two of our sites in Japan and in Europe got awarded in the categories ‘Process intelligence and innovation’ as well as ‘Facility integration’. This illustrates that Takeda is constantly investing into state of the art facilities applying best in class process as well as digital standards. Both projects in Hikari and in Grange Castle also demonstrate that significant technology improvements for small molecule modalities are still achievable, both in a cost as well as in a time efficient manner."

Takeda’s Hikari plant is located in the south of Japan in the Yamaguchi prefecture. One of Takeda`s largest plants, it features advanced production systems for active pharmaceutical ingredients (API), drug formulation, biological products, and others offering a stable supply of high-quality pharmaceutical products throughout the world. The project at the Hikari site is a four-story building designed to elevate pharmaceutical packaging operations to a new industrial standard. The facility features highly automated end-to-end packaging equipment, including "end of line" case packers, automated guided vehicles (AGVs) and robots to feed the automated storage and retrieval system (ASRS). Additionally, the site developed and introduced an automatic line clearance system (ALC) with 360° cameras and laser sensors utilizing artificial intelligence (AI) to help significantly increase efficiency in the pharmaceutical packaging process. Takeda’s Hikari plant exemplifies how novel application of commercially available and custom developed process manufacturing tools leads to superior results and advanced process understanding.

The Grange Castle site in Ireland is located in the Dublin area, and it includes three manufacturing facilities. The production facility which now got awarded by the ISPE is a standalone, high containment, cutting-edge production facility dedicated to manufacturing Takeda’s treatment for multiple myeloma. The application of good design practices and superior conceptual planning led to the excellent integration of facility and process. The innovative design as an ‘all-in-one’ facility incorporates the entire end-to-end production process from active pharmaceutical ingredients to drug product and packaging under one roof. This significantly simplifies the supply chain for one of Takeda´s global oncology products to ensure unconstrained availability to patients worldwide.

"The design teams have implemented best-in-class digital technologies to guarantee the facilities use the latest developments in paperless automation, robotics and augmented reality. This strategic use of digital and automated systems has led to a state-of-the-art facility design that positions Takeda as a frontrunner in our industry," added Gunter Baumgartner, head of Global Engineering at Takeda.

An official ceremony of all winning projects and awards is planned at this year’s ISPE Annual Meeting & Expo in Boston, MA, in November.

About the ISPE Facility of the Year Awards Program
Established in 2004, the Facility of the Year Awards (FOYA) recognizes state-of-the-art projects utilizing new, innovative technologies to improve the quality of products, reduce the cost of producing high-quality medicines, and demonstrate advances in project delivery. The FOYA program provides a platform for the pharmaceutical science and manufacturing industry to showcase its accomplishments in facility design, construction, and operations, while sharing the development of new applications of technology and cutting-edge approaches. For more information, visit View Source

On April 28, 2021 OmniSeq, an innovator in next generation sequencing in oncology, reported the New York State Department of Health’s Clinical Laboratory Evaluation Program has approved the OmniSeq INSIGHTSM test (Press release, OmniSeq, APR 28, 2021, View Source,the%20OmniSeq%20INSIGHTSM%20test.&text=OmniSeq%20INSIGHT%20is%20a%20tissue%2Dbased%2C%20next%20generation%20sequencing%20test. [SID1234579250]). The test detects genomic variants, genomic signatures, and immune gene expression, providing physicians with clinically actionable evidence to inform therapeutic treatment decisions and identify potential clinical trial options for patients with late-stage solid tumor cancers.

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The test will be commercially available to U.S.-based clinicians exclusively through Labcorp and globally to biopharmaceutical companies through Labcorp Drug Development. Throughout Canada, the test will be available through Dynacare, a Labcorp company.

"The launch of OmniSeq INSIGHT represents the continued evolution of our commitment to innovation and to the delivery of the most advanced, comprehensive solid tumor profiling assay," said Margot Schoenborn, Chief Executive Officer, OmniSeq. "It is designed to detect and characterize the genomic and immune features of patients’ cancer tumors to quickly guide more precise, individualized treatment decisions for patients to ensure they receive the best personalized medicine options available."

OmniSeq INSIGHT is a tissue-based, next generation sequencing test. It has been clinically and analytically validated for all solid tumors, interrogating gene alterations that are targets identified for therapy. Completely unique to the test is the integration of immune expression profiling, which detects genes involved in the anti-cancer immune response and tumor-immune mechanisms including low-expressing genes involved in inflammatory signaling. The combined profiling of molecular and immune genes delivers an unparalleled and powerful new tool to help physicians more effectively select personalized therapies and immunotherapies, as well as match patients to clinical trials based on multi-immune marker analyses.

OmniSeq INSIGHT delivers the distinct advantage of leveraging three technologies to better inform physicians in selecting the most appropriate therapies or clinical trials for their patients. DNA sequencing is used to detect base substitutions, insertions, deletions, copy number alterations, tumor mutational burden and microsatellite instability. RNA sequencing is employed for detection of known and novel gene arrangements in order to maximize detection of fusion events and gene expression profiling; this also provides differentiating insight into critical tumor-immune interactions. Additionally, PD-L1 expression is measured by immunohistochemistry using FDA-approved assays based on the tumor type tested.

OmniSeq INSIGHT can be used in both diagnostic and drug development settings. It is actively integrated into numerous drug development programs and can be configured as an effective discovery tool, screening tool or clinical trial assay and can drive companion diagnostics development and commercialization initiatives. OmniSeq INSIGHT is offered to global biopharmaceutical customers directly and through Labcorp Drug Development, which collectively have an extensive track record in validating assays across key regulatory standards, including CLIA, CLEP, CE-IVD and FDA under an ISO 13485 quality management system for medical devices.

On April 28, 2021 Boundless Bio, a next-generation precision oncology company developing innovative therapeutics directed against extrachromosomal DNA (ecDNA) in aggressive cancers, reported the closing of an oversubscribed $105 Million Series B financing (Press release, Boundless Bio, APR 28, 2021, View Source [SID1234578623]). With the proceeds of the financing, the company will advance into the clinic multiple ecDNA-directed therapeutic programs and the accompanying ecDNA Harboring Oncogenes (ECHO) companion diagnostic and expand its pipeline of novel cancer therapies targeting ecDNA.

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RA Capital Management and Nextech Invest co-led the financing, with participation from a top-tier syndicate of funds, including Fidelity Management & Research Company LLC, Redmile Group, Wellington Management, Surveyor Capital (a Citadel company), PFM Health Sciences, and Logos Capital. Current investors ARCH Venture Partners, City Hill Ventures, Vertex Ventures HC, GT Healthcare Capital Partners, Boxer Capital of Tavistock Group, and Alexandria Venture Investments also participated in the Series B. In conjunction with the financing, Jakob Loven, Ph.D., Partner at Nextech Invest, will join the Boundless Bio Board of Directors.

"Boundless Bio has made tremendous progress since launching in 2019," said Zachary Hornby, President and Chief Executive Officer of Boundless Bio. "Over the past two years our team has custom built a platform, called Spyglass, that enables us to interrogate ecDNA in cancer and reveal key therapeutically targetable liabilities in ecDNA-driven, gene amplified tumors. From these efforts, we have discovered and validated three ecDNA-essential targets and have initiated drug discovery against each. In addition, we are developing the ECHO companion diagnostic assay to identify patients with ecDNA-driven tumors. This financing round and stellar investor syndicate reflects the investment community’s appreciation for the high unmet clinical need of patients with oncogene amplified cancers and the promise of our innovative approach to targeting ecDNA to improve and prolong the lives of these patients."

ecDNA are circular units of DNA that contain functional genes and are highly transcriptionally active. ecDNA constitute a primary driver of gene amplification and copy number heterogeneity in cancer. ecDNA are present in many solid tumor cancers but generally not in healthy cells. Boundless Bio’s Spyglass platform combines proprietary ecDNA model systems with bespoke analytical tools to enable Boundless Bio scientists to interrogate ecDNA cancer biology to discover new cancer targets that are synthetically lethal in ecDNA-driven cancers. Boundless Bio is leveraging these insights to discover and develop innovative new precision medicines targeting the underlying cellular machinery that enables ecDNA to function in cancer.

"We invest in oncology companies with compelling science," said Jakob Loven, Ph.D., Partner at Nextech Invest. "ecDNA is a transformative new area of cancer biology, and Boundless Bio is the clear leader in the rapidly emerging field. The Boundless team has made remarkable progress since the company formation, demonstrating that ecDNA biology is tractable as a therapeutic approach and advancing a powerful platform, exciting early drug programs and a promising companion diagnostic approach. We are eager to work with the experienced Boundless team to transform cancer care for underserved patients with gene amplified cancers."

"RA Capital has been following the Boundless Bio story for some time now and believes that the team has developed industry-leading expertise in the biology that underlies high unmet need, gene amplified tumors," said Zach Scheiner, Ph.D., Principal at RA Capital Management. "Boundless Bio has shown ecDNA to be a driver of both tumor growth and resistance to targeted therapies, and the team is poised to make significant therapeutic advances in this exciting new field. We are pleased to support their efforts to help bring these potentially transformative therapies to patients in need."