On April 12, 2021 Lonza reported an expansion to its popular PyroTec PRO Automated Robotic Solution for endotoxin testing (Press release, Lifescience Newswire, APR 12, 2021, View Source [SID1234577978]). The new PyroWave Reader add-on has been designed specifically for use with the sustainable PyroGene Recombinant Factor C (rFC) Assay. This brings a third test type option to the platform, allowing QC microbiologists to choose the endotoxin test method best suited for their testing needs. The PyroTec PRO Solution, now compatible with Lonza’s PYROGENT-5000 Turbidimetric LAL (Limulus Amebocyte Lysate) Assay, Kinetic-QCL Chromogenic LAL Assay and the PyroGene rFC Assay, expands the options available for streamlined, automated endotoxin testing.

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The PyroWave Reader add-on is built upon the original release of the PyroTec PRO Automated System that includes two absorbance readers for traditional LAL-based assays. Able to easily accommodate different assay types in the same run and powered by the world-class WinKQCL Endotoxin Analysis Software, this complete system further increases the efficiencies and data integrity gained from automated endotoxin testing.

The PyroGene rFC Assay is an animal-free method for endotoxin detection that works through a single enzymatic step. It has been shown to be equivalent to other photometric endotoxin methods that use LAL to detect endotoxins according to the parameters listed in the USP chapter <1225> "Validation of Compendial Procedures". These parameters include linearity, specificity, precision, accuracy, and limit of detection.

The need for accurate and dependable endotoxin testing technology continues to grow, especially with the pharmaceutical industry increasingly focusing on the development of innovative biotherapeutics that carry a higher risk of endotoxin contamination. Through process optimization and automation of routine manual tasks, the PyroTec PRO Automated Robotic Solution enables users to streamline and improve the performance of the QC laboratory, increasing lab efficiency and productivity. Automated endotoxin testing can also substantially reduce the potential for human error, enhancing the accuracy, reliability, and traceability of results.

On April 12, 2021 C4X Discovery Holdings plc (AIM: C4XD), a pioneering Drug Discovery company, reported that its subsidiary, C4X Discovery Limited ("C4XD", "C4X Discovery" or the "Company"), has signed an exclusive worldwide licensing agreement with Sanofi (NASD: SNY, PAR: SAN – "Sanofi "), worth up to €414 million, for C4XD’s oral pre-clinical IL-17A inhibitor programme (Press release, C4X Discovery, APR 12, 2021, View Source [SID1234577886]). Under the terms of the agreement, C4XD will receive an upfront payment of €7 million and could receive up to a further €407 million in potential development, regulatory and commercialisation milestones, of which €11 million is in pre-clinical milestones, in addition to single digit royalties.

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Under the license, Sanofi will develop and commercialise an oral therapy for the treatment of inflammatory diseases, a multi-billion dollar market. The IL-17 family of cytokines are strong inducers of inflammation and are implicated in a variety of autoimmune diseases including psoriasis, psoriatic arthritis and ankylosing spondylitis. Current treatments targeting IL-17 are monoclonal antibodies administered via an injection. There is an urgent need for safe and efficacious oral small molecule therapies to increase the number of patients able to access IL-17 targeted drugs and expand availability into new inflammatory disease indications. C4XD’s small molecule IL-17A inhibitor programme can selectively block IL-17 activity in vivo whilst maintaining molecular size of the molecule in the traditional "drug-like" range suitable for oral administration. Sanofi will continue to work with the C4XD team to access its unique and proprietary 4D Conformetrix technology, as the programme advances towards clinical studies.

Clive Dix, CEO of C4X Discovery, said: "We are proud to be working with Sanofi to create much needed oral therapies in the underserved inflammatory disease space. While antibody therapies have demonstrated the potential of IL-17 inhibition in the generation of highly effective treatments, the injectable route means many patients currently do not have access to the medicines that can change their lives. We believe that our small molecule programme has the potential to create high value, efficacious and convenient oral IL-17 therapeutics for this large market. The Psoriasis market alone is estimated to be worth c.$24 billion per annum by 20271, and when combined with Sanofi’s development expertise our programme has the potential to address a number of indications.

"This is the second significant agreement for a C4XD programme and marks a major milestone for the Company, not only validating the strength of our Drug Discovery expertise, but also our strategy to drive shareholder value through early-stage revenue generating deals. With Indivior progressing our molecule for opioid addiction through a Phase I clinical trial and now our partnership with Sanofi driving potential next generation oral IL-17 therapies, we look forward with confidence to further develop our portfolio and deliver additional novel small molecule drug candidates tackling significant patient needs."

On April 12, 2021 Replimune Group, Inc. (Nasdaq: REPL), a biotechnology company developing oncolytic immuno-gene therapies derived from its Immulytic platform, reported additional data supporting the multiple mechanisms of action for its lead programs, RP1 and RP2, during two presentations at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2021 being held virtually April 10-15, 2021 and May 17-21, 2021 (Press release, Replimune, APR 12, 2021, View Source [SID1234577905]).

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"We developed Replimune’s Immulytic platform with the intention of developing therapies with both enhanced tumor killing potency and with an enhanced ability to initiate a systemic anti-tumor immune response. This pre-clinical and clinical biomarker data provides further evidence that these objectives are being achieved, and that RP1 and RP2 are able to initiate a potent systemic immune response against a patient’s cancer," said Robert Coffin, PhD, President and Chief Research and Development Officer, Replimune.

Details of the presentations are as follows:

Abstract Title: Clinical biomarker studies with two fusion-enhanced versions of oncolytic HSV (RP1 and RP2) alone and in combination with nivolumab in cancer patients indicate potent immune activation – Abstract #: LB180

In patients dosed with RP1 in combination with nivolumab or single agent RP2 alone and in combination with nivolumab, immunohistochemistry for CD8 and PD-L1 from paired tumor biopsies demonstrated robust and increased infiltration of CD8+ T cells and PD-L1 expression across different tumor types, including reversal of T cell exclusion following prior combined treatment with ipilimumab and nivolumab in melanoma.
A significant increase in the expression levels of genes associated with innate and adaptive immune activation and genes previously reported to be associated with responsiveness to anti-PD1 therapy was demonstrated.
In patients dosed with RP2 monotherapy, an increase in CD8+ T cell infiltration as well as robust changes in expression of key tumor and immune cell signalling pathway genes was observed.
Peripheral blood T cell receptor (TCR) sequencing indicated the expansion of existing T cell clones and generation of new T cell clones.
Increased CD8+ T cell infiltration and PD-L1 expression, coupled with changes in TCR clonal expansion in PBMC samples, suggest systemic immune activation.
This presentation is now available for on-demand viewing on the AACR (Free AACR Whitepaper) Annual Meeting 2021 website linked here and also posted to the presentations section of the Replimune website and linked here.

RP1 is Replimune’s lead Immulytic product candidate and is based on a proprietary new strain of herpes simplex virus (HSV) engineered to maximize tumor killing potency, the immunogenicity of tumor cell death and the activation of a systemic anti-tumor immune response through the expression of a GALV-GP R- fusogenic protein and GM-CSF. RP2 is a derivative of RP1 that expresses an anti-CTLA-4 antibody-like molecule intended to provide targeted and potent delivery to the sites of immune response initiation in the tumor and draining lymph nodes, with the goal of focusing systemic immune-based efficacy on tumors and limiting off-target toxicity.

Abstract Title: Immunomodulatory effects of a novel, enhanced potency gibbon ape leukemia virus (GALV) fusogenic membrane glycoprotein-expressing herpes simplex virus platform with increased efficacy combined with anti PD-1 therapy – Abstract #1917

This poster presentation is a collaboration between Replimune and The Institute of Cancer Research, London, UK.

In a histological examination of tumors injected with RP1 or RP2, large areas of necrosis in syngeneic mouse tumours were observed, even in a model where GALV-GP R- is not functional. In models where GALV-GP R- is functional, including in human xenograft tumors in nude mice (which have no adaptive immune system, but retain innate, e.g. NK cell mediated, immune function), GALV-GP R- was observed to give anti-tumor activity in both injected and in uninjected tumors, whereas a virus without GALV-GP R- only exhibited anti-tumor activity in injected tumors. These effects in uninjected tumors were presumed to result from enhanced innate immune activation mediated by GALV-GP R-.
RP1 increased PD-L1 expression, particularly on neutrophils, and increased CD3 T cell infiltration in injected and contralateral tumors.
Profound effects on the gene expression profile were also seen in both injected and contralateral tumors which are consistent with potent and broad immune activation. These were significantly greater than that seen with single agent anti-PD1, and were further enhanced when RP1 was combined with anti-PD1.
This presentation is now available for on-demand viewing on the AACR (Free AACR Whitepaper) Annual Meeting 2021 website linked here and also posted to the presentations section of the Replimune website and linked here.

"RP1 and RP2 represent attractive potential treatment modalities with the ability to self-amplify, kill through multiple mechanisms and promote anti-tumour immune responses," said Professor Kevin Harrington, PhD, Professor in Biological Cancer Therapies at The Institute of Cancer Research, London, and Consultant Clinical Oncologist at The Royal Marsden NHS Foundation Trust ​in the UK. "These data show that RP1 increases PD-L1 expression, increases CD3 T cell infiltration in injected and contralateral tumors, and has profound effects on the gene expression profile in both injected and non-injected tumors which are consistent with potent and broad immune activation. These benefits are then further enhanced by treatment with anti-PD1 creating the potential for an attractive treatment option for patients with difficult to treat tumor types who are currently underserved."

Opdivo is a registered trademark of Bristol Myers Squibb.

On April 12, 2021 XOMA Corporation (Nasdaq: XOMA) ("XOMA" or the "Company") reported the closing of its previously announced underwritten registered public offering of 1,600,000 depositary shares, each representing a 1/1000th fractional interest in a share of the Company’s 8.375% Series B Cumulative Perpetual Preferred Stock, with liquidation preference equivalent to $25.00 per depositary share (Press release, Xoma, APR 12, 2021, View Source [SID1234577921]). The offering resulted in net proceeds of approximately $38.0 million after deducting underwriting discounts and commissions, but before expenses. The Company expects to use the net proceeds of this offering to fund the segregated dividend account and the remaining net proceeds for general corporate purposes, including funding future acquisitions of milestone and royalty rights associated with drug development programs with third-party funding. The depositary shares will be listed on Nasdaq under the symbol "XOMAO" and are expected to begin trading within 30 days.

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Book-running managers for this offering were B. Riley Securities, Inc., National Securities Corporation, Ladenburg Thalmann & Co. Inc., and William Blair & Company. Co-managers were Aegis Capital Corp., Boenning & Scattergood, Inc., Incapital LLC, and Northland Capital Markets.

The depositary shares were offered under the Company’s shelf registration statement on Form S-3, which was declared effective by the U.S. Securities and Exchange Commission ("SEC"). The offering of these depositary shares was made only by means of a prospectus supplement and accompanying base prospectus, which were filed with the SEC. A copy of the prospectus and prospectus supplement relating to these securities may be obtained on the website of the SEC at View Source or from the offices of B. Riley Securities, Inc., 1300 17th Street North, Suite 1300, Arlington, Virginia 22209, or by telephone at (703) 312-9580 or by emailing [email protected].

This press release does not constitute an offer to sell or the solicitation of an offer to buy, nor shall there be any sale of the depositary shares in any state or jurisdiction in which such offer, solicitation, or sale would not be permitted.

On April 12, 2021 Innovent Biologics, Inc. ("Innovent", HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of cancer, metabolic, autoimmune and other major diseases, reported with Eli Lilly and Company ("Lilly",NYSE: LLY) that the results of the Phase 3 ORIENT-3 study were released today in an oral presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2021 (Press release, Innovent Biologics, APR 12, 2021, View Source [SID1234577938]).

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ORIENT-3 is a randomized, open-label, Phase 3 clinical trial evaluating TYVYT (sintilimab injection) versus docetaxel as a second-line treatment for advanced or metastatic squamous non-small cell lung cancer (sqNSCLC). A total of 290 patients whose cancer had progressed following first-line treatment with platinum-based chemotherapy were enrolled. Based on the primary analysis population (280 patients, excluding patients on the docetaxel arm who received immunotherapy prior to disease progression), TYVYT (sintilimab injection) demonstrated a statistically significant improvement in overall survival (OS) compared to docetaxel, meeting the pre-specified primary endpoint. The median OS was 11.79 months for patients on the TYVYT (sintilimab injection) arm and 8.25 months for those on the docetaxel arm (HR=0.74, 95% CI: 0.56-0.96, P=0.02489). The median progression-free survival (PFS) as assessed by investigators was 4.30 months versus 2.79 months (HR=0.52, 95% CI: 0.39-0.68, P<0.00001), and the confirmed objective response rate (ORR) was 25.5 percent versus 2.2 percent (P<0.00001), respectively. Safety was consistent with previous studies of TYVYT (sintilimab injection), and no new safety signals were identified.

Professor Yuankai Shi, principal investigator of ORIENT-3, Associate Dean of Cancer Hospital, Chinese Academy of Medical Sciences and Chairman of Cancer Foundation of China, stated: "Lung cancer is the leading cause of cancer death globally, of which non-small cell lung cancer accounts for 80 to 85 percent. In the past few decades, drug development of non-small cell lung cancer has mainly focused on nonsquamous non-small cell lung cancer, while drug development of squamous non-small cell lung cancer has been slower due to its unique epidemiological, histopathological and molecular characteristics. In China, specifically, the approved options for second-line immunotherapy to treat squamous non-small cell lung cancer are even more limited. The ORIENT-3 study showed that the anti-PD-1 monoclonal antibody sintilimab significantly improved overall survival for the second-line treatment of squamous non-small cell lung cancer patients, which is of great clinical value. We hope that the positive results of ORIENT-3 can help more squamous non-small cell lung cancer patients."

"TYVYT (sintilimab injection) was the first anti-PD-1 inhibitor included in the New Catalogue of the National Reimbursement Drug List in 2019," said Dr. Hui Zhou, Vice President of Medical Science and Strategy Oncology of Innovent. "In August 2020, the NMPA accepted a new indication application for TYVYT (sintilimab injection) in combination with chemotherapy for first-line treatment of squamous NSCLC. In the ORIENT-3 study, sintilimab as second-line monotherapy demonstrated a significantly improved survival benefit for patients with advanced squamous non-small cell lung cancer, and we look forward to the potential approval of this indication, to help more patients with this type of lung cancer."

"We are excited about these results, showing TYVYT (sintilimab injection) significantly improved overall survival in this patient population. This study underscores the joint commitment from Lilly and Innovent to provide innovative treatment options to patients with lung cancer," said Dr. Wang Li, Senior Vice President of Lilly China and Head of Lilly China Drug Development and Medical Affairs. "We would like to thank the patients, the investigators, the clinical trial centers and our colleagues from Innovent that are involved in the study. We look forward to working together to potentially bring this new treatment option to people in China with squamous non-small cell lung cancer."

About Squamous NSCLC

Lung cancer is a malignancy with the highest morbidity and mortality in China. NSCLC accounts for about 80 to 85 percent of lung cancer. Approximately 70 percent of people with NSCLC have locally advanced or metastatic NSCLC at initial diagnosis, rendering many of those patients with no chance of radical resection. Meanwhile, even after radical surgery, patients still have a high chance of recurrence and eventually die from disease progression. About 30 percent of people in China with non-small cell lung cancer have tumors of the squamous subtype and there are limited approved second-line therapies for these patients. Therefore, there remains a huge unmet medical need in China.

About the ORIENT-3 Trial

ORIENT-3 is a randomized, open-label, multi-center, Phase 3 clinical trial to evaluate the efficacy and safety of TYVYT (sintilimab injection) as second-line therapy for advanced or metastatic sqNSCLC (ClinicalTrials.gov, NCT 03150875). The primary endpoint is overall survival (OS). The secondary endpoints include progression-free survival (PFS) as assessed by investigators based on RECIST v1.1, objective response rate (ORR) and safety profile.

A total of 290 patients were enrolled in ORIENT-3 and randomized in a 1:1 ratio to receive either TYVYT (sintilimab injection) 200mg or docetaxel every three weeks. The patients received treatment until radiographic disease progression, unacceptable toxicity or any other conditions that require treatment discontinuation.

About TYVYT (Sintilimab Injection)

TYVYT (sintilimab injection), an innovative drug with global quality standards jointly developed in China by Innovent and Lilly, has been granted marketing approval by the NMPA (National Medical Products Administration) for the treatment of relapsed or refractory classic Hodgkin’s lymphoma after two lines or later of systemic chemotherapy, and is included in the 2019 Guidelines of Chinese Society of Clinical Oncology for Lymphoid Malignancies. In February 2021, TYVYT (sintilimab injection) was approved by the China NMPA in combination with pemetrexed and platinum chemotherapy as first-line therapy for the treatment of nonsquamous non-small cell lung cancer. TYVYT (sintilimab injection) was included in the National Reimbursement Drug List (NRDL) in November 2019 as the first PD-1 inhibitor and the only PD-1 included in the list in that year.

Currently TYVYT (sintilimab injection) has three supplemental New Drug Applications ("sNDA") under review by the NMPA. In August 2020, the NMPA accepted the sNDA for TYVYT (sintilimab injection) in combination with gemcitabine and platinum chemotherapy as first-line therapy in squamous NSCLC. In January 2021, the NMPA accepted the sNDA for TYVYT (sintilimab injection) in combination with BYVASDA (bevacizumab injection) as first-line therapy in Hepatocellular Carcinoma (HCC) and the sNDA for TYVYT (sintilimab injection) as second-line therapy in squamous NSCLC. Besides, in May 2020, TYVYT (sintilimab injection) monotherapy met the primary endpoint of overall survival in the Phase 2 ORIENT-2 study as second-line therapy in patients with advanced or metastatic esophageal squamous cell carcinoma.

TYVYT (sintilimab injection), is a type of immunoglobulin G4 monoclonal antibody, which binds to PD-1 molecules on the surface of T-cells, blocks the PD-1 / PD-Ligand 1 (PD-L1) pathway and reactivates T-cells to kill cancer cells. Innovent is currently conducting more than 20 clinical studies with TYVYT (sintilimab injection) to evaluate its safety and efficacy in a wide variety of cancer indications, including more than 10 registrational or pivotal clinical trials. Meanwhile, Innovent is conducting clinical research studies on TYVYT (sintilimab injection) worldwide.