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The NDA of the Novel Anti-PD-1 mAb Serplulimab of Henlius Accepted by NMPA and Proposed to be Granted Priority Review

On April 22, 2021 Shanghai Henlius Biotech, Inc. (2696.HK) reported that the New Drug Application (NDA) of serplulimab injection (HLX10), a novel anti-PD-1 monoclonal antibody (mAb), for the treatment of unresectable or metastatic microsatellite instability-high (MSI-H) solid tumors that fail to respond to the standard therapy, has been accepted by the National Medical Products Administration (NMPA) and proposed to be granted priority review (Press release, Shanghai Henlius Biotech, APR 22, 2021, View Source [SID1234578383]). Serplulimab is potentially to be the first anti-PD-1 mAb in MSI-H solid tumors in China. For this indication, patients are screened for specific MSI-H tumor markers, rather than classifying the tumor types, covering a wide range of cancer types. Henlius adopts the "Combo+Global" development strategy for serplulimab, focusing on indication differentiation and combination therapy, with a total of 10 clinical trials conducted worldwide.

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The co-leading principal investigator of serplulimab Phase 2 clinical trial in unresectable or metastatic microsatellite instability-high or mismatch repair-deficient (MSI-H/dMMR) solid tumors, Professor Shukui Qin of Cancer Center of Nanjing Jinling Hospital, said, "Serplulimab showed excellent anti-tumor activity in preclinical and early-stage clinical studies, and the results of the Phase 2 clinical study in MSI-H solid tumors also states the favorable safety and efficacy. We hope that this China-developed novel PD-1 inhibitor will be launched as soon as possible, so that more patients with solid tumors could be accessible to high quality immunotherapy new options."

Executive Director, Chief Executive Officer and President of Henlius, Mr. Wenjie Zhang, said, "Serplulimab is the core innovative mAb of Henlius. Focusing on combination immunotherapy and international clinical trials, we have built up a differentiation development strategy for the product. Steady progress has been made in all clinical studies. We are very grateful to all the subjects, physicians and colleagues that have contributed to the NDA acceptance of serplulimab. We will push forward the clinical process in more indications as soon as possible and look forward to benefiting more patients around the world."

Several pivotal Phase 3 clinical trials covering comprehensive cancer types with high incidence

With the "Combo+Global" strategy, steady progress has been made in the clinical studies of 2 monotherapies and 8 combination therapies of serplulimab with chemotherapy, in-house VEGF and EGFR targets mAbs. Henlius actively carries out combination therapies that cover a wide range of tumor types with high incidence such as lung cancer, esophageal cancer, hepatocellular cancer, gastric cancer, head and neck cancer, and implements differentiation clinical development based on the Chinese cancer characteristics. Among them, while there are few explorations in the gastric cancer neoadjuvant/adjuvant area of PD-1 inhibitors, Henlius has conducted Phase 3 clinical studies in this field, leading the clinical trial progress around the globe, with the aim of enabling gastric cancer patients to benefit from the early line of immunotherapy. What’s more, the company has achieved all-around layout in the first-line of lung cancer, and has entered pivotal Phase 3 clinical trials in first-line squamous non-small cell lung cancer (sqNSCLC), first-line non-squamous non-small cell lung cancer (nsqNSCLC) and first-line small cell lung cancer (SCLC). The NDA filing of HLX10 in combination with chemotherapy for the first-line treatment of sqNSCLC in China will also be expected in the second half of 2021.

The all-around international layout to benefit emerging markets

The manufacturing and development of serplulimab is strictly in accordance with international standards and its manufacturing facility based in Shanghai has passed the European Union (EU) and China GMP certification. Henlius developed the international layout for serplulimab, which has been approved for clinical trials in China, the United States, the EU and other countries and regions. About 2000 patients have been enrolled in China, Turkey, Poland, Ukraine, Russia, etc., which shows confidence and recognition on the quality of the product in the international market. Apart from conducting international trials of HLX10, Henlius also actively seeks for international cooperation opportunities with the aim of benefiting more patients in the world, especially patients in emerging markets. Henlius has reached a collaboration agreement with PT Kalbe Genexine Biologics (KG Bio), upon which KG Bio is granted exclusive rights to develop and commercialize serplulimab in relation to its first monotherapy and two combination therapies in 10 Southeast Asian countries.

With the continuous development of the "Combo+Global" strategy, Henlius continues to build a diversified pipeline of innovative drug candidates with serplulimab as the lead, actively accelerating innovation and improving innovation efficiency, and committing to bringing affordable and high-quality innovative biologics to patients around the world.

About MSI-H solid tumors

The defect of mismatch repair (MMR) that can lead to base mismatch or insert in microsatellites during DNA replication, and the accumulation of incorrect bases usually causes microsatellite instability (MSI)[1]. MSI-H often occurs in several cancer types, such as endometrial cancer, colorectal cancer, gastric cancer, renal cell carcinoma, ovarian cancer, etc[2]. Studies have revealed that the prevalence of MSI-H across all tumor types is 14%[3]. Patients who suffer from this disease usually have higher response rates for immune checkpoint inhibitors[4-5]. Thus, MSI-H is becoming a more and more important biomarker for the immunotherapy predictions of patients with solid tumors. If the patient is MSI-H positive and meets the treatment criteria, the corresponding immunotherapy can be carried out without screening tumor sites and pathological classification, which aligns with the advanced concept of precision medicine and is applicable to a wide range of cancer types. Currently, the U.S. Food and Drug Administration (US FDA) has approved PD-1 target mAb for the treatment of second-line MSI-H/dMMR advanced solid tumors and first/second-line MSI-H/dMMR colorectal cancers. While there are still no anti-PD-1 mAb approved for MSI-H/dMMR advanced solid tumors in China, the treatment needs are far from being met.

Jazz Pharmaceuticals Prices $1.5 Billion Senior Secured Notes Offering

On April 22, 2021 Jazz Pharmaceuticals plc (Nasdaq: JAZZ) (the "Company" or "Jazz") reported the pricing of the previously announced offering (the "Offering") of $1.5 billion in an aggregate principal amount of 4.375% senior secured notes due 2029 (the "Notes") by Jazz Securities Designated Activity Company, a direct wholly owned subsidiary of the Company (the "Issuer") (Press release, Jazz Pharmaceuticals, APR 22, 2021, View Source [SID1234578382]). The Notes will mature on January 15, 2029 and will bear an interest rate of 4.375%. The Notes will be guaranteed by the Company and certain of its subsidiaries. The Offering is expected to close on April 29, 2021 subject to customary closing conditions.

The aggregate principal amount of the Notes to be issued in the Offering decreased to $1.5 billion from the anticipated $2.7 billion announced on April 20, 2021, a decrease of $1.2 billion. This reduction corresponds to the equivalent anticipated increase in term loan borrowings under our new senior secured credit facilities (the "New Senior Secured Credit Facilities") in connection with the previously announced proposed acquisition of GW Pharmaceuticals plc ("GW") (the "Acquisition") from $2.65 billion to approximately $3.85 billion.

The Company expects to use the net proceeds from the Notes and Acquisition date borrowings under the new senior secured credit facilities, together with cash on hand to fund the cash consideration payable in connection with the Acquisition of GW, the refinancing of certain of the Company’s indebtedness (including the Company’s existing senior secured credit facility) and fees and expenses in connection with the foregoing. The Offering is not conditioned on the closing of the Acquisition. If (1) the Acquisition is consummated without the Company entering into the New Senior Secured Credit Facilities, (2) the Acquisition has not been consummated on or before August 3, 2021 (or such later date to which such date may be extended pursuant to the terms of the Transaction Agreement, dated February 3, 2021, among the Company, GW and Jazz Pharmaceuticals UK Holdings Limited (the "Transaction Agreement") or (3) the Transaction Agreement is terminated in accordance with its terms, the Issuer will be required to redeem all of the Notes at a redemption price equal to 100% of their principal amount plus accrued and unpaid interest to, but excluding, the redemption date.

The Notes will be offered and sold only to persons reasonably believed to be qualified institutional buyers pursuant to Rule 144A under the U.S. Securities Act of 1933, as amended (the "Securities Act") that are located in the United States, Canada, France, Ireland, Luxembourg, the United Kingdom, and Bermuda and to certain non-U.S. persons outside the United States pursuant to Regulation S under the Securities Act that are located in Canada, France, Ireland, Luxembourg, the United Kingdom, and Bermuda. The Notes have not been registered under the Securities Act or any state securities law and may not be offered or sold in the United States absent registration or an applicable exemption from the registration requirements of the Securities Act and applicable state laws.

This press release does not constitute an offer to sell or a solicitation of an offer to purchase the Notes or any other securities and does not constitute an offer, solicitation or sale in any state or jurisdiction in which such an offer, solicitation or sale would be unlawful.

DermTech Introduces PLAplus with Improved Sensitivity for Early Detection of Melanoma

On April 22, 2021 DermTech, Inc. (NASDAQ: DMTK) ("DermTech"), a leader in precision dermatology enabled by a non-invasive skin genomics platform, reported the launch of DermTech PLAplusTM, its next generation test for the enhanced early detection of melanoma (Press release, DermTech International, APR 22, 2021, View Source [SID1234578381]). PLAplus delivers objective and actionable information to guide clinical management decisions for skin lesions suspicious of melanoma.

The new PLAplus test adds TERT (Telomerase Reverse Transcriptase) promoter DNA driver mutation analyses to the current RNA gene expression based Pigmented Lesion Assay (PLA), which includes LINC00518 and PRAME. TERT is individually associated with histopathologic features of aggressiveness and poor survival in melanoma. The combined tests (LINC00518 and PRAME, plus TERT) elevate the sensitivity from 91%1 to 97% and maintain a negative predictive value of >99%, resulting in a less than 1% probability of missing melanoma2,3. By combining RNA gene expression and DNA mutation analyses, PLAplus provides a highly accurate non-invasive genomic test for enhanced early melanoma detection.

"Identifying melanoma at its earliest stages provides patients with the highest cure rate, and TERT promoter mutations are independently associated with poor overall survival and more aggressive disease," said Laura Ferris, M.D., Ph.D., Associate Professor, Dermatology, University of Pittsburgh and senior author of Risk Stratification of Severely Dysplastic Nevi by Non-Invasively Obtained Gene Expression and Mutation Analyses.2 "Having additional genomic information to objectively assess disease risk beyond what can be ascertained visually can help physicians make an earlier, more accurate diagnosis."

"DermTech is thrilled about the addition of DNA TERT promoter mutation analyses to our test menu for the enhanced early detection of melanoma," said Claudia Ibarra, chief operating officer at DermTech. "As always, it is our commitment to deliver high quality testing and laboratory services to our patients and clinicians, and PLAplus is a prime example of this."

The National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology recognize the use of pre-diagnostic non‑invasive genomic patch testing for melanoma, like the DermTech PLATM, to help guide biopsy decisions for lesions suspicious of melanoma. There are over 21 peer reviewed publications summarizing its clinical validity and utility of the DermTech PLATM in studies of over 7,000 patients.

The lowest sensitivity of DermTech PLA demonstrated in our clinical studies to date
Jackson SR et al. J of SKIN. 2020; 4(2):124-129
Gerami P et al. J Am Acad Dermatol. 2017;76(1):114- 120.e2

Puma Biotechnology to Host Conference Call to Discuss First Quarter Financial Results

On April 22, 2021 Puma Biotechnology, Inc. (NASDAQ: PBYI), a biopharmaceutical company, reported that it will host a conference call at 1:30 p.m. PDT/4:30 p.m. EDT on Thursday, May 6, 2021, following the release of its first quarter 2021 financial results (Press release, Puma Biotechnology, APR 22, 2021, View Source [SID1234578380]).

The call may be accessed by dialing 1-877-709-8150 (domestic) or 1-201-689-8354 (international). Please dial in at least 10 minutes in advance and inform the operator that you would like to join the "Puma Biotechnology Conference Call." A live webcast of the conference call and presentation slides may be accessed on the Investors section of the Puma Biotechnology website at View Source A replay of the call will be available approximately one hour after completion of the call and will be archived on Puma’s website for 90 days.

Illumina and Kartos Therapeutics Announce New Oncology Partnership to Develop an NGS-Based TP53 Companion Diagnostic

On April 22, 2021 Illumina, Inc. (NASDAQ: ILMN) and Kartos Therapeutics, Inc. reported a new partnership to co-develop a TP53 companion diagnostic (CDx) based on the content of Illumina’s comprehensive genomic profiling assay, TruSight Oncology 500 (TSO 500) (Press release, Illumina, APR 22, 2021, View Source [SID1234578379]). This companion diagnostic for multiple hematologic indications will be the first to use TSO 500 with peripheral whole blood as a diagnostic sample type.

"With this partnership, Illumina will expand the TruSight Oncology offerings into hematologic malignancies," said Phil Febbo, MD, Chief Medical Officer of Illumina. "By leveraging our technology and harnessing the expertise at Kartos, we continue to advance Illumina’s commitment to develop standardized, globally distributable tools for precision oncology."

The initial focus of the collaboration will be the co-development of multiple CDx claims in blood cancers for Kartos’ KRT-232, a potent and selective oral MDM2 inhibitor that activates p53 to drive tumor cell death in TP53 wild-type cancers.

"Kartos is dedicated to developing novel, targeted therapeutics that meaningfully improve the lives of patients with cancer," said Jesse McGreivy, MD, Chief Executive Officer and Chief Medical Officer at Kartos. "This partnership will allow us to capitalize on TSO 500 as we explore the expanded use of KRT-232, which offers a unique mechanism to restore the function of p53, one of the most critical tumor suppressor proteins, resulting in apoptosis of malignant cells across a variety of hematologic and solid tumor types."

The collaboration with Kartos builds on a solid history and varied portfolio of Illumina’s oncology partnerships with industry leaders, with the united goal of advancing cancer diagnostics and precision medicine.

About TruSight Oncology 500

TSO 500 is a Research Use Only comprehensive pan-cancer assay designed to identify 523 known and emerging tumor biomarkers. TSO 500 utilizes both DNA and RNA from tumor samples to identify key variants critical for cancer development and progression, such as small DNA variants, fusions, and splice variants. Based on the content of TSO 500, Illumina will be adding an in vitro diagnostic (IVD) test to the TruSight Oncology product family. This comprehensive tumor profiling assay will have similar chemistry and analytics to TSO 500.