On March 5, 2021 Loxo Oncology at Lilly, a research and development group of Eli Lilly and Company (NYSE: LLY), reported that The Lancet has published data from the pirtobrutinib (previously referred to as LOXO-305) global Phase 1/2 BRUIN clinical trial in relapsed or refractory chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), mantle cell lymphoma (MCL), and other non-Hodgkin’s lymphomas (Press release, Eli Lilly, MAR 5, 2021, View Source [SID1234576138]). Pirtobrutinib is an investigational, highly selective, non-covalent Bruton’s tyrosine kinase (BTK) inhibitor.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The data in the publication include key findings previously presented at the 2020 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting. The publication includes safety and efficacy data for 323 relapsed or refractory patients (including 170 with CLL/SLL, 61 with MCL, 26 with Waldenström’s macroglobulinemia and 66 with other B-cell lymphomas) that were enrolled to the BRUIN Phase 1/2 trial as of September 27, 2020.

"Patients with B-cell malignancies who have been previously treated with the most commonly used regimens represent an area of growing and urgent unmet need", said Anthony Mato, M.D., director of the CLL Program at Memorial Sloan Kettering Cancer Center and lead author of The Lancet paper. "These data establish that the third generation BTK inhibitor pirtobrutinib possesses a compelling efficacy and safety profile with the potential to address this exact unmet need."

"While covalent BTK inhibitors and venetoclax have transformed the treatment of CLL, we now see many patients needing new therapeutic alternatives," said Brian Koffman, MDCM (retired), chief medical officer of the CLL Society. "In the coming years, we envision that this need will grow, and we are pleased to see data that pirtobrutinib may be a new option for these patients."

"We are extremely pleased to see the pirtobrutinib data from the ongoing Phase 1/2 BRUIN study published in The Lancet and shared with the broader clinical community", said David Hyman, M.D., chief medical officer of Loxo Oncology at Lilly. "The data to date from this study have continued to strengthen our conviction that pirtobrutinib has the potential to meaningfully improve the inadequate treatment options available to CLL and MCL patients who have been previously treated with the main treatment classes of today’s standard of care. We are focused on quickly advancing the pirtobrutinib development program, including through a series of Phase 3 studies that will be initiated over the course of 2021."

In addition to the Phase 1/2 BRUIN clinical trial, Loxo Oncology at Lilly plans to initiate four global, randomized Phase 3 studies for pirtobrutinib in 2021, three in CLL and one in MCL.

About Pirtobrutinib (LOXO-305)
Pirtobrutinib is an investigational, oral, highly selective, non-covalent Bruton’s tyrosine kinase (BTK) inhibitor. BTK plays a key role in the B-cell antigen receptor signaling pathway, which is required for the development, activation and survival of normal white blood cells, known as B-cells, and malignant B-cells. BTK is a validated molecular target found across numerous B-cell leukemias and lymphomas including chronic lymphocytic leukemia, mantle cell lymphoma, Waldenström macroglobulinemia, and marginal zone lymphoma. Currently available BTK inhibitors irreversibly inhibit BTK and the long-term efficacy of these therapies can be limited by acquired resistance, most commonly through BTK C481 mutations. In rapidly growing tumors with inherently high rates of BTK turnover, resistance to covalent BTK therapies may be the result of incomplete target inhibition. Pirtobrutinib was designed to reversibly bind BTK, deliver consistently high target coverage regardless of BTK turnover rate, preserve activity in the presence of the C481 acquired resistance mutations, and avoid off-target kinases that have complicated the development of both covalent and investigational non-covalent BTK inhibitors. Interested patients and physicians can contact the Loxo Oncology at Lilly Physician and Patient BTK Clinical Trial Hotline at 1-855-LOXO-305 or email [email protected].

About the BRUIN Phase 1/2 Trial
This first-in-human, global, multi-center Phase 1/2 trial evaluates pirtobrutinib as a single agent in patients with previously treated chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), or non-Hodgkin’s lymphomas (NHL). The trial includes a Phase 1 dose escalation phase and a Phase 2 dose expansion phase. The Phase 1 dose escalation enrolls patients with CLL/SLL or NHL who have received at least two prior lines of therapy and have progressed or are intolerant to standard of care. The dose escalation phase followed a "3+3" design with pirtobrutinib dosed orally in 28-day cycles. As dose cohorts were cleared, additional patients could enroll in cleared cohorts and intra-patient dose escalation was permitted. The primary objective of the Phase 1 portion of the trial is to determine the maximum tolerated dose and recommended Phase 2 dose. Key secondary objectives include measures of safety, pharmacokinetics, and anti-tumor activity (i.e. Overall Response Rate (ORR) and Duration of Response, as determined by appropriate histology-specific response criteria). In the Phase 2, patients are enrolled across various cohorts, depending on disease type and prior therapy. The primary endpoint for Phase 2 is ORR. Secondary endpoints include duration of response (DOR), overall survival (OS), safety, and pharmacokinetics (PK).

About Loxo Oncology at Lilly
Loxo Oncology at Lilly was created in December 2019, combining the Lilly Research Laboratories oncology organization and Loxo Oncology, which was acquired by Lilly in early 2019. Loxo Oncology at Lilly brings together the focus and spirit of a biotech with the scale and resources of large pharma, with the goal of rapidly delivering impactful new medicines for people with cancer. Our approach centers on creating new oncology medicines that unequivocally work early in clinical development and will matter to patients.

On March 5, 2021 BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160), a commercial-stage biotechnology company focused on developing and commercializing innovative medicines worldwide, reported that a supplemental Biologics License Application (sBLA) for anti-PD1 antibody tislelizumab was accepted by the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) for treatment in the second- or third-line setting of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) who have progressed on prior platinum-based chemotherapy (Press release, BeiGene, MAR 5, 2021, View Source [SID1234576137]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We are excited to submit the third marketing application for tislelizumab from its broad program in lung cancer which consists of five completed or ongoing Phase 3 trials. Results from our Phase 3 RATIONALE 303 trial demonstrated improved overall survival over chemotherapy in advanced NSCLC patients who have progressed after treatment with chemotherapy at its interim analysis, which we have been able to file quickly with the CDE for its review," commented Yong (Ben) Ben, M.D., Chief Medical Officer, Immuno-Oncology at BeiGene. "With three approvals for tislelizumab in China, as well as three sBLAs under review, we are excited to continue to build upon our broad development program for tislelizumab, a potentially differentiated checkpoint inhibitor and explore additional opportunities with our new partner Novartis."

RATIONALE 303 Trial of Tislelizumab Compared to Docetaxel in Patients with Locally Advanced or Metastatic NSCLC Who Progressed on Prior Platinum-Based Chemotherapy

The sBLA is supported by clinical results from the Phase 3 RATIONALE 303 trial, a randomized, open-label, multicenter global Phase 3 clinical trial (NCT03358875) designed to evaluate the efficacy and safety of tislelizumab compared to docetaxel in the second- or third-line setting in patients with locally advanced or metastatic NSCLC who have progressed on a prior platinum-based chemotherapy. The primary endpoint of the trial is OS in all patients (the ITT population) and in patients with high PD-L1 expression; key secondary endpoints include objective response rate (ORR), duration of response (DoR), progression-free survival (PFS), and safety. A total of 805 patients in 10 countries across Asia, Europe, the Americas, and Oceania were randomized 2:1 to either the tislelizumab arm or the docetaxel arm.

As announced in November 2020, RATIONALE 303 met the primary endpoint of OS at the planned interim analysis, as recommended by the independent Data Monitoring Committee (DMC). The safety profile of tislelizumab was consistent with the known risks with no new safety signals identified. BeiGene expects to present results from the RATIONALE 303 trial at an upcoming medical conference in the first half of 2021.

About Non-Small Cell Lung Cancer

In China, the lung cancer incidence rate is increasing.i There were approximately 815,563 new cases of lung cancer in China in 2020, and it is the leading cause of cancer-related death in both men and women, with approximately 714,699 deaths in China in 2020.ii Non-small cell lung cancer (NSCLC) is the most common form of lung cancer, accounting for approximately 80 to 85 percent of all cases.iii

About Tislelizumab

Tislelizumab (BGB-A317) is a humanized IgG4 anti-PD-1 monoclonal antibody specifically designed to minimize binding to FcγR on macrophages. In pre-clinical studies, binding to FcγR on macrophages has been shown to compromise the anti-tumor activity of PD-1 antibodies through activation of antibody-dependent macrophage-mediated killing of T effector cells. Tislelizumab is the first drug from BeiGene’s immuno-oncology biologics program and is being developed internationally as a monotherapy and in combination with other therapies for the treatment of a broad array of both solid tumor and hematologic cancers.

The China National Medical Products Administration (NMPA) has granted tislelizumab full approval for first-line treatment of patients with advanced squamous non-small cell lung cancer (NSCLC) in combination with chemotherapy. Tislelizumab has also received conditional approval from the NMPA for the treatment of patients with classical Hodgkin’s lymphoma (cHL) who received at least two prior therapies, and for the treatment of patients with locally advanced or metastatic urothelial carcinoma (UC) with PD-L1 high expression whose disease progressed during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. Full approval for these indications is contingent upon results from ongoing randomized, controlled confirmatory clinical trials.

In addition, three supplemental Biologics License Applications for tislelizumab have been accepted by the Center for Drug Evaluation (CDE) of the NMPA and are under review for first-line treatment of patients with advanced non-squamous NSCLC in combination with chemotherapy, for the second- or third-line treatment of patients with locally advanced or metastatic NSCLC who progressed on prior platinum-based chemotherapy, and for previously treated unresectable hepatocellular carcinoma.

Currently, 15 potentially registration-enabling clinical trials are being conducted in China and globally, including 12 Phase 3 trials and two pivotal Phase 2 trials.

In January 2021, BeiGene and Novartis entered into a collaboration and license agreement to develop, manufacture, and commercialize tislelizumab in North America, Europe, and Japan.

Tislelizumab is not approved for use outside of China.

About the Tislelizumab Clinical Program

Clinical trials of tislelizumab include:

Phase 3 trial comparing tislelizumab with docetaxel in the second- or third-line setting in patients with NSCLC (NCT03358875);
Phase 3 trial comparing tislelizumab to salvage chemotherapy in patients with relapsed/refractory classical Hodgkin Lymphoma (NCT04486391);
Phase 3 trial in patients with locally advanced or metastatic urothelial carcinoma (NCT03967977);
Phase 3 trial of tislelizumab in combination with chemotherapy versus chemotherapy as first-line treatment for patients with advanced squamous NSCLC (NCT03594747);
Phase 3 trial of tislelizumab in combination with chemotherapy versus chemotherapy as first-line treatment for patients with advanced non-squamous NSCLC (NCT03663205);
Phase 3 trial of tislelizumab in combination with platinum-based doublet chemotherapy as neoadjuvant treatment for patients with NSCLC (NCT04379635);
Phase 3 trial of tislelizumab combined with platinum and etoposide versus placebo combined with platinum and etoposide in patients with extensive-stage small cell lung cancer (NCT04005716);
Phase 3 trial comparing tislelizumab with sorafenib as first-line treatment for patients with hepatocellular carcinoma (HCC; NCT03412773);
Phase 2 trial in patients with previously treated unresectable HCC (NCT03419897);
Phase 3 trial comparing tislelizumab with chemotherapy as second-line treatment for patients with advanced esophageal squamous cell carcinoma (ESCC; NCT03430843);
Phase 3 trial of tislelizumab in combination with chemotherapy as first-line treatment for patients with ESCC (NCT03783442);
Phase 3 trial of tislelizumab versus placebo in combination with chemoradiotherapy in patients with localized ESCC (NCT03957590);
Phase 3 trial of tislelizumab combined with chemotherapy versus placebo combined with chemotherapy as first-line treatment for patients with gastric cancer (NCT03777657);
Phase 2 trial in patients with MSI-H/dMMR solid tumors (NCT03736889); and
Phase 3 trial of tislelizumab combined with chemotherapy versus placebo combined with chemotherapy as first-line treatment in patients with nasopharyngeal cancer (NCT03924986).

On March 5, 2021 Illumina, Inc.’s (NASDAQ: ILMN) reported NextSeq 550Dx platform and associated reagent kits received medical device registration in Russia, as have reagents for the MiSeqDx which was approved previously as a medical device (Press release, Illumina, MAR 5, 2021, View Source [SID1234576123]). Both of these in vitro diagnostic (IVD)-ready solutions are available to customers and third-party developers to create diagnostic solutions using the technology. These registrations will catalyze the expansion of sequencing-based clinical diagnostics across the country.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Sequencing platforms, and the reagents that drive them, must be approved separately in Russia by the medical device regulatory agency, Roszdravnadzor. Illumina’s strategic partner in Russia and CIS, R-Pharm, led the regulatory process and this is the first approval of complete sets of sequencing instruments plus reagents.

"Having the two IVD-platforms available to assay developers to expand the clinical use of Next Generation Sequencing-based (NGS) molecular diagnostics will be a great boost to testing for genetic diseases and oncology in Russia," said Paula Dowdy, Senior Vice President and General Manager of Illumina, Europe Middle East and Africa. "The NextSeq 550Dx is ideal for high throughput sequencing at large, federal hospitals, and the desktop MiSeqDx is well suited to the laboratory facilities of standard clinical centers."

"These registrations are a significant step in bringing NGS technologies closer to patients, many of whom live near the smaller municipal and regional clinics. Bringing NGS diagnostics, with accurate and validated results, will be a huge benefit to patients," said deputy Director General of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Professor Mikhail Maschan.

Director of the Tomsk National Research Medical Center, correspondent member of the Russian Academy of Sciences, Vadim Stepanov, said: "Genetics and molecular biology are the core of clinical science because the majority of diseases originate from genetic mechanisms in cells, tissues and organs. Registration of Illumina’s products as medical devices allows to add the most modern technologies to clinical practice."

"We are pleased that our partnership with Illumina, a global leader in human genome sequencing, will help Russian patients benefit from improved diagnosis and precision healthcare," said Alexey Repik, R-Pharm Chairman of the Board.

On March 4, 2021 PerkinElmer, Inc. (NYSE: PKI), a global leader committed to innovating for a healthier world, reported that it has priced an offering of $400.0 million aggregate principal amount of 2.550% Senior Notes due 2031 at an issue price of 99.965% of the principal amount and $400.0 million aggregate principal amount of 3.625% Senior Notes due 2051 at an issue price of 99.999% of the principal amount (Press release, PerkinElmer, MAR 4, 2021, View Source [SID1234576104]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The issuance of the notes is expected to close on March 8, 2021, subject to customary closing conditions. The notes will pay interest on a semi-annual basis.

PerkinElmer plans to use approximately $561 million of the net proceeds of the offering to repay amounts borrowed under its senior unsecured revolving credit facility to fund a portion of the purchase price for its acquisition of Oxford Immunotec Global PLC. PerkinElmer expects to use the remaining net proceeds of the offering to repay at maturity a portion of its outstanding €300.0 million aggregate principal amount of 0.600% senior notes due 2021.

The joint book-running managers for the offering are J.P. Morgan Securities LLC, BofA Securities, Inc., and Wells Fargo Securities, LLC.

The offering is being made pursuant to an effective registration statement on Form S-3 (including a prospectus) filed with the U.S. Securities and Exchange Commission ("SEC"). Prospective investors should read the prospectus forming a part of that registration statement and the prospectus supplement related to the offering and the other documents that PerkinElmer has filed with the SEC for more complete information about the company and this offering. These documents are available at no charge by visiting EDGAR on the SEC website at www.sec.gov. Alternatively, copies of the prospectus supplement and the accompanying prospectus relating to the offering can be obtained by calling one of the joint book-running managers at the following: J.P. Morgan Securities LLC collect at 1-212-834-4533 or BofA Securities, Inc. toll-free at 1-800-294-1322.

This press release shall not constitute an offer to sell or the solicitation of an offer to buy the notes, nor shall there be any offer, solicitation or sale of the notes in any jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such jurisdiction.

On March 4, 2021 ALX Oncology Holdings Inc. ("ALX Oncology") (Nasdaq: ALXO), a clinical-stage immuno-oncology company developing therapies that block the CD47 checkpoint pathway, and Tallac Therapeutics, Inc. ("Tallac"), a privately held biopharmaceutical company harnessing the power of innate and adaptive immunity to fight cancer, reported a collaboration to jointly develop, manufacture, and commercialize a novel class of cancer immunotherapeutics (Press release, Tallac Therapeutics, MAR 4, 2021, View Source [SID1234579742]). Under the terms of the agreement, ALX Oncology and Tallac will share equally in the cost of research and development and any profits or losses incurred.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The collaboration builds on ALX Oncology’s expertise in developing therapies that block the CD47 checkpoint pathway and expands its immuno-oncology pipeline. The collaboration also extends Tallac’s pipeline of next generation immunotherapies derived from its novel Toll-like Receptor Agonist Antibody Conjugate ("TRAAC") platform. The companies will leverage their respective scientific and technical expertise to advance an anti-SIRPα antibody conjugated to a Toll-like receptor 9 ("TLR9") agonist for targeted activation of both the innate and adaptive immune systems.

"We are excited to partner with ALX Oncology in the development of next-generation breakthrough cancer immunotherapies," said Hong I. Wan, Ph.D., President, Chief Executive Officer and co-founder of Tallac. "TLR9 agonists are a class of immunotherapy that generate both innate and adaptive immune responses which may produce robust and durable anti-cancer immunity for patients with advanced-stage cancers. While intratumoral TLR9 agonists have clinically validated this pathway, systemic administration has been unsuccessful, limiting clinical utility in broader patient populations. With Tallac’s TRAAC technology, we now have a way to target this pathway systemically, which could expand the clinical benefit to a much broader patient population. To date, we have generated promising preclinical data with multiple TRAAC molecules that demonstrates the potential of this pathway. The goal of our collaboration with ALX Oncology is to advance SIRPα TRAAC, a systemically delivered TLR9 agonist targeting dendritic cells via SIRPα receptors, enabling a powerful innate and adaptive anti-tumor immune response."

"Collaborating with Tallac and their novel TRAAC platform broadens ALX Oncology’s therapeutic strategies to activate the innate immune system and SIRPα TRAAC complements our lead product candidate, ALX148," said Jaume Pons, Ph.D., Founder, President and Chief Executive Officer of ALX Oncology. "While ALX148 is an antagonistic molecule designed to maximize the activity of a wide array of anticancer agents by the blockade of the CD47 myeloid checkpoint, SIRPα TRAAC is an agonistic molecule that directly activates dendritic cells and enables a coordinated innate and adaptive immune response against cancer. Since SIRPα is expressed on both dendritic cells and a range of tumor types, SIRPα TRAAC may enable an effective immune activation response in advanced cancer settings. We are excited about this potentially transformative approach and the possible benefits to patients that are in need of new treatment options."

Conference Call on March 5 at 8:30 a.m. EST

ALX Oncology and Tallac will host a conference call on Friday, March 5, 2021 at 8:30 a.m. EST to further discuss the collaboration.

To access the conference call, please dial (844) 467-7655 (local) or (409) 983-9840 (international) at least 10 minutes prior to the start time and refer to conference ID 4117088. Presentation slides will be available to download under "News & Events" (see "Events") in the investors section of the ALX Oncology website at www.alxoncology.com.