On May 9, 2023 Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of cancer, autoimmune, metabolic, ophthalmology and other major diseases, and Eli Lilly and Company ("Lilly", NYSE: LLY), jointly reported that the National Medical Products Administration (NMPA) of China has approved the supplemental New Drug Application (sNDA) for TYVYT (sintilimab injection) in combination with bevacizumab and chemotherapy (pemetrexed and cisplatin) in patients with epidermal growth factor receptor (EGFR)-mutated non-squamous non-small cell lung cancer (NSCLC) who progressed after EGFR tyrosine kinase inhibitor (TKI) therapy (Press release, Innovent Biologics, MAY 9, 2023, View Source [SID1234631307]). It makes TYVYT (sintilimab injection) globally the first PD-1 inhibitor approved for patients with EGFR-mutated non-squamous NSCLC that progressed after EGFR-TKI therapy, which is a breakthrough in the field of immunotherapy.

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This is the seventh NMPA-approved indication of TYVYT (sintilimab injection). The first six indications of TYVYT (sintilimab injection) are included in the National Reimbursement Drug List (NRDL), making TYVYT (sintilimab injection) the only PD-1 inhibitor for the first-line treatment of five high-incidence cancer types in the NRDL – including non-squamous NSCLC, squamous NSCLC, hepatocellular carcinoma, esophageal squamous cell carcinoma, and gastric cancer. TYVYT (sintilimab injection) is also the first and the only immunotherapy medicine for gastric cancer in the NRDL. This is also the eighth NMPA-approved indication of BYVASDA (bevacizumab injection).

This new approval in China was based on the results of a randomized, double-blind, multi-center, prospective Phase 3 clinical trial (ORIENT-31, NCT03802240) evaluating TYVYT (sintilimab injection) ± BYVASDA (bevacizumab injection) + chemotherapy (pemetrexed and cisplatin) for the treatment of patients with EGFR-mutated non-squamous NSCLC who progressed after EGFR-TKI therapy.

In the second interim analysis (data cutoff date: March 31st, 2022), in the intent-to-treat (ITT) population, based on the assessment by the Independent Radiographic Review Committee (IRRC), significant and clinically meaningful PFS benefit was sustained with sintilimab plus bevacizumab plus chemotherapy compared with chemotherapy alone (median PFS: 7.2 months vs. 4.3 months; HR=0.51, p<0.0001). Additionally, the key secondary endpoints of objective response rate (ORR) and duration of response (DOR) were improved with sintilimab plus bevacizumab plus chemotherapy, compared with chemotherapy alone.

As of data cutoff date July 4th, 2022, a trend towards overall survival (OS) benefit with sintilimab plus bevacizumab and chemotherapy was observed although the median OS for chemotherapy was prolonged due to crossover after progression in chemotherapy group. The median OS for sintilimab plus bevacizumab plus chemotherapy and chemotherapy alone were 21.1 months vs 19.2 months, HR=0.98. After adjusting for crossover, the OS HR ranged from 0.79 to 0.84. In the exploratory analyses of quality of life, compared with the chemotherapy alone, sintilimab plus bevacizumab and chemotherapy showed longer median time-to-deterioration of the Global Health Status Dimension Score of EORTC Quality of Life Questionnaire Core 30 (QLQ-C30). The safety profile of this study was consistent with that observed in previously reported studies of sintilimab and bevacizumab, without new or unexpected safety signals.

The first interim analysis results of ORIENT-31 were published in The Lancet Oncology on July 28, 2022[i]. The second interim analysis results were published in The Lancet Respiratory Medicine on May 5, 2023[ii].

The principal investigator of the ORIENT-31 Study, Prof. Shun Lu from the Oncology Department of Shanghai Chest Hospital, stated, "Different from the western population, about half of the Chinese patients with NSCLC have EGFR mutations. EGFR-TKI targeted therapy is the first line treatment choice in NSCLC patients with EGFR sensitive mutation. However, almost all patients will eventually develop TKI-resistance and progression of disease and there are no good treatment options for EGFR-TKI failed NSCLC population[iii]. The ORIENT-31 study is globally the first prospective, randomized and double-blind Phase 3 study that demonstrated that PD-1 inhibitor ± bevacizumab combined with chemotherapy can significantly prolong PFS in EGFR-mutant non-squamous NSCLC population who have failed EGFR-TKI treatment. In addition, compared with standard platinum-based chemotherapy, sintilimab and bevacizumab combined with chemotherapy improved the ORR and DOR, showing survival benefit trend as well as improvement in quality of life. The approval of this indication brings a new treatment option for EGFR-mutated non-squamous NSCLC patients who have failed EGFR-TKI treatment, benefiting more Chinese patients."

Dr. Michael Yu, Founder, Chairman and CEO of Innovent, stated, "Despite proven efficacy in broad types of cancer, immunotherapy has rarely made breakthroughs in the treatment of driver gene-positive non-squamous NSCLC patients. We are excited about the results of ORIENT-31 study and this new approval marks the first immunotherapy combination therapy approved for patients with driver gene-positive non-squamous NSCLC in China, and making TYVYT the first PD-1 inhibitor approved for driver gene-positive non-squamous NSCLC globally. Innovent will continue our commitment to innovation and contribute to the ‘Healthy China 2030’ strategy."

Dr. Hui Zhou, Senior Vice President of Innovent, stated, "Lung cancer is a malignant tumor with the highest mortality rate and incidence in China, representing a large unmet medical need[iv]. The new approval of TYVYT is another important clinical development milestone, bringing new hope to the broader lung cancer patients with EGFR mutation. Innovent will continue to develop more novel therapies to address unmet clinical needs and bring more effective treatment options to patients in China and globally. "

Mr. Ben Basil, President and General Manager of Lilly China, stated, "Since its debut in 2018, TYVYT has been approved consecutively six indications including lymphoma, lung cancer, liver cancer, esophageal cancer to gastric cancer, and all six indications have been included in the National Reimbursement Drug List (NRDL), benefiting millions of Chinese patients. I am very excited to see another indication approved today, bringing a brand new treatment option to NSCLC patients who have failed EGFR-TKI treatment in China. TYVYT sets a great example for our partnership with Innovent. We will continually work with our local partners in bringing more innovative drugs to Chinese patients, continuously making contributions to the ‘Healthy China 2030’ blueprint."

Dr. Li Wang, Lilly Corporate Senior Vice President, Head of China Drug Development & Medical Affairs Center, stated, "The ORIENT-31 study is globally the first study in immunotherapy to confirm benefits in EGFR positive lung cancer patients who have failed EGFR-TKI treatment. The two interim analyses have demonstrated encouraging clinical results, breaking the dilemma of EGFR-TKI resistance. With the newly approved indication, TYVYT provides a new treatment option and brings new hope to patients with EGFR-mutated non-squamous NSCLC who progressed after EGFR-TKI therapy in China."

About the ORIENT-31 Study

ORIENT-31 is a randomized, double-blind, multi-center Phase 3 clinical study conducted in China evaluating sintilimab, with or without bevacizumab, combined with chemotherapy (pemetrexed and cisplatin) in patients with EGFR-mutated locally advanced or metastatic nsqNSCLC who have progressed following EGFR TKI treatment (ClinicalTrials.gov, NCT03802240). The primary endpoint is PFS as assessed by IRRC based on RECIST v1.1. The secondary endpoints include overall survival (OS), PFS as assessed by investigators, ORR and safety.

About Sintilimab

Sintilimab, marketed as TYVYT (sintilimab injection) in China, is a PD-1 immunoglobulin G4 monoclonal antibody co-developed by Innovent and Eli Lilly and Company. Sintilimab 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[v]. Innovent is currently conducting more than 20 clinical studies of sintilimab to evaluate its safety and efficacy in a wide variety of cancer indications, including more than 10 registrational or pivotal clinical trials.

In China, sintilimab has been approved for seven indications and included in the National Reimbursement Drug List (NRDL) for six indications. The updated NRDL reimbursement scope of TYVYT (sintilimab injection) include:

For the treatment of unresectable locally advanced, recurrent or metastatic gastric or gastroesophageal junction adenocarcinoma;
For the treatment of unresectable locally advanced, recurrent or metastatic esophageal squamous cell carcinoma;
For the treatment of unresectable locally advanced or metastatic non-squamous non-small cell lung cancer lacking EGFR or ALK driver gene mutations;
For the treatment of unresectable locally advanced or metastatic squamous non-small cell lung cancer;
For the treatment of unresectable or metastatic hepatocellular carcinoma with no prior systematic treatment;
For the treatment of relapsed or refractory classic Hodgkin’s lymphoma after two lines or later of systemic chemotherapy.
Additionally, sintilimab has been approved in combination with bevacizumab and chemotherapy (pemetrexed and cisplatin) for the treatment of patients with EGFR-mutated nsqNSCLC who progressed after EGFR-TKI therapy.

Besides, two clinical studies of sintilimab have met their primary endpoints:

Phase 2 study of sintilimab monotherapy as second-line treatment of esophageal squamous cell carcinoma;
Phase 3 study of sintilimab monotherapy as second-line treatment for squamous NSCLC with disease progression following platinum-based chemotherapy.
About BYVASDA (bevacizumab injection)

BYVASDA is a recombinant humanized anti-VEGF monoclonal antibody drug. Vascular endothelial growth factor (VEGF) is an important factor in angiogenesis that is highly expressed by the endothelial cells in most human tumors. An anti-VEGF antibody binds VEGF-A selectively with high affinity and blocks its binding to VEGF-2 receptors on the surface of vascular endothelial cells, thereby inhibiting signaling pathways such as PI3K-Akt/PKB and Ras-Raf-MEK-ERK. BYVASDA produces anti-tumor effects by inhibiting the growth, proliferation and migration of vascular endothelial cells, blocking angiogenesis, reducing vascular permeability, blocking blood supply to tumor tissues, inhibiting the proliferation and metastasis of tumor cells and inducing apoptosis in tumor cells[vi]. In China, BYVASDA is approved for eight indications including advanced non-small cell lung cancer, metastatic colorectal cancer, adult recurrent glioblastoma, advanced or unresectable hepatocellular carcinoma, epithelial ovarian, fallopian tube, or primary peritoneal cancer and cervical cancer, seven of which are included in the NRDL.

On May 9, 2023 Gilead Sciences, Inc. (Nasdaq: GILD) reported the acquisition of all outstanding shares of XinThera, a privately held biotech company in San Diego (Press release, Gilead Sciences, MAY 9, 2023, View Source [SID1234631305]). The acquisition complements Gilead’s existing clinical development priorities by adding additional pipeline assets for well-validated targets in oncology and inflammation.

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Through the acquisition, Gilead gains rights to a portfolio of small molecule inhibitors targeting PARP1 for oncology and MK2 for inflammatory diseases that could enter clinical trials later this year. Both programs have the potential to address multiple indications, offering broad development opportunities alone and in combination with Gilead’s portfolio.

"The team at XinThera has developed research assets with the potential to target the DNA damage repair pathway in treating cancer and direct the body’s immune response in inflammatory diseases, both of which may improve outcomes for people living with these diseases," said Flavius Martin, M.D., Executive Vice President, Research, Gilead Sciences. "Guided by our scientific framework, this acquisition will allow us to further expand our early pipeline of diverse assets that will continue to fuel our durable late-phase portfolio."

"Gilead and XinThera share similar missions to discover new therapies to treat cancer and inflammatory diseases, which drive our determination to unlock the body’s ability to better respond to these diseases," said Chris LeMasters, who served as XinThera CEO. "We are eager to join Gilead and together explore the potential of our precision medicines as critical components of the next generation of therapies targeting diseases with high unmet need."

First-generation, dual PARP1/2 inhibitors have been shown to be highly efficacious in the treatment of patients with homologous recombination deficiency (HRD) tumors with BRCA-mutations such as breast, ovarian, prostate, and pancreatic cancers, but their use is limited due to hematological toxicities. PARP1 selective inhibitors have the potential to mitigate the hematological toxicities seen in first-generation, dual PARP1/2 inhibitors and enable combination with a wide variety of DNA-damaging agents, including systemic chemotherapy and targeted agents such as Trodelvy (sacituzumab govitecan-hziy). For important safety information, including boxed warning, for Trodelvy, please see full Prescribing Information.

The financial terms of the agreement were not disclosed. Beginning in the first quarter of 2022, consistent with recent industry communications from the U.S. Securities and Exchange Commission (SEC), Gilead no longer excludes acquired IPR&D expenses from its non-GAAP financial measures. We expect the transaction with XinThera to reduce Gilead’s GAAP and non-GAAP 2023 EPS by approximately $0.12 – $0.15.

On May 9, 2023 Zai Lab Limited (NASDAQ: ZLAB; HKEX: 9688) reported financial results for the first quarter of 2023, along with recent product highlights and corporate updates (Press release, Zai Laboratory, MAY 9, 2023, View Source [SID1234631304]).

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"Our first quarter results and progress continue to demonstrate Zai Lab’s potential global best-in-class portfolio and track record of execution, despite challenges from China’s re-opening at the beginning of the year," said Dr. Samantha Du, Founder, Chairperson and Chief Executive Officer of Zai Lab. "The positive topline readout from the Phase 3 EMERGENT-3 trial of KarXT in schizophrenia and the positive interim analysis from the innovaTV 207 Phase 2 study of TIVDAK in head and neck cancer further support our belief that these are important treatment options for patients in China and globally. We are also very excited about the U.S. Food and Drug Administration (FDA) Advisory Committee’s unanimous recommendation in support of approval for sulbactam-durlobactam, the first pathogen-targeted therapy for patients with serious and life-threatening infections caused by Acinetobacter."

"Recently, we expanded our lung cancer franchise and enriched our global oncology pipeline with a next generation DLL3 ADC program, ZL-1310," said Dr. Du. "This global ADC program demonstrates our continued focus on the ADC space. This product complements our lung cancer franchise, and we will leverage our strong capabilities to develop ZL-1310, and look forward to seeing results in patients."

"I look forward to leading Zai into its next transformational stage of growth, productivity, and global opportunities. To better support me and help meet the strategic and operational needs of our business during this next stage of growth, we are happy to announce that we have promoted Josh Smiley to President and Chief Operating Officer. Josh’s rich experience and strategic vision will help us further grow as a leading global biopharmaceutical company and deliver on our mission to improve human health and on our corporate strategic goals for driving innovation in China and beyond," Dr. Du concluded.

"I am very excited about what is in store for us in the next few years that positions Zai Lab to be a leader in biopharma innovation," said Josh Smiley. "We are pleased with the overall environment this year in China for companies like Zai Lab with innovative therapies that meet significant unmet medical needs. We expect strong growth momentum to continue throughout the remainder of this year."

"With respect to our 2023 strategic priorities, we have made progress toward the Biologics License Application (BLA) approval of efgartigimod for generalized myasthenia gravis (gMG) and the BLA submission for subcutaneous (SC) efgartigimod for gMG in China, initiation of a bridging study for KarXT in schizophrenia in Greater China, initiation of a registrational study for bemarituzumab in first-line gastric cancer in Greater China and a full data readout of the Tumor Treating Fields LUNAR study in non-small cell lung cancer. We are also advancing our proprietary pipeline with global rights, including initiating a global Phase 1 study for ZL-1218 (CCR8) and moving ZL-1102 (IL-17 Humabody) into full global development," Mr. Smiley concluded.

Recent Product Highlights and Corporate Updates
Zai Lab has established a differentiated portfolio and pipeline of 22 potentially global best-in-class and/or first-in-class therapies, including 13 in late-stage development. During the first quarter of 2023, we had a number of exciting developments with respect to our products and product candidates, including the following:
1

Commercial Products
We continued to increase access to our commercial products, including through increased sales for ZEJULA (niraparib), new NRDL listings for QINLOCK (ripretinib) and NUZYRA (omadacycline), and increased supplemental insurance listings for Optune:
•Sales growth for ZEJULA: Net product revenue for ZEJULA continued to increase in the first quarter of 2023, growing 44.2% compared to the first quarter of 2022. We believe ZEJULA remains on track to become the leader in its asset class for ovarian cancer in China starting this year.
•The National Reimbursement Drug List (NRDL) implementation: The updated NRDL released by China’s National Healthcare Security Administration (NHSA) officially took effect on March 1, 2023. It has been updated to include both QINLOCK and NUZYRA.
•Supplemental insurance plan coverage (as of March 31, 2023): Optune was listed in 96 regional customized commercial health insurance plans guided by provincial or municipal governments (or supplemental insurance plans), up from 87 as of December 31, 2022 and 37 as of March 31, 2021.
Product Candidate Developments
We continued to advance our product candidates through our research and development and commercial operations, including the following developments with respect to our clinical trials and regulatory approvals:
Oncology
•TIVDAK (tisotumab vedotin, ADC):
–In April 2023, Zai Lab partner Seagen Inc. (Seagen) presented the interim analysis for the Phase 2 innovaTV 207 study in head and neck cancer at the 2023 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting. At data cutoff (November 28, 2022), confirmed that the objective response rate was 40% (95% confidence interval: 16.3, 67.7), with 1 complete response and 5 partial responses. The safety profile was generally consistent with that observed across TIVDAK monotherapy clinical studies.
–In February 2023, Seagen completed global target patient enrollment for the Phase 3 confirmatory innovaTV 301 study in second- or third-line recurrent or metastatic (r/m) cervical cancer, with a potential topline data readout by year-end 2023. Zai Lab is participating in the ongoing extension study in mainland China, Hong Kong, Macau and Taiwan (collectively, Greater China).
•KRAZATI (adagrasib, KRASG12C):
–Zai Lab partner Mirati Therapeutics, Inc. (Mirati) announced the inclusion of adagrasib as the only KRAS inhibitor in the National Comprehensive Cancer Network (NCCN) guidelines for Central Nervous System Cancers for patients with KRASG12C -mutated non-small cell lung cancer (NSCLC) with central nervous system (CNS) metastases and for KRASG12C-mutation positive pancreatic adenocarcinoma cancer patients.
–In April 2023, Mirati presented updated clinical data for adagrasib as a targeted treatment for pancreatic ductal adenocarcinoma (PDAC), biliary tract cancer (BTC), and other solid tumors harboring a KRASG12C mutation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Plenary series. Data was concurrently published in the Journal of Clinical Oncology.
•Bemarituzumab (FGFR2b): In March 2023, Zai Lab obtained Clinical Trial Application (CTA) approval for the Phase 3 FORTITUDE-101 study of bemarituzumab plus chemotherapy, versus placebo plus chemotherapy, in first-line gastric cancer with FGFR2b overexpression.
•Odronextamab (CD20xCD3): In March 2023, Zai Lab completed enrollment in China for the registrational global ELM-2 Phase 2 trial in B-Cell Non-Hodgkin Lymphoma.
•ZL-2313 (BLU-945, EGFR): In April 2023, Zai Lab partner Blueprint Medicines Corporation (Blueprint) presented novel real-world data showing first-line osimertinib had worse outcomes in EGFR L858R+ vs. ex19del+ NSCLC at the 2023 AACR (Free AACR Whitepaper) Annual Meeting. Data also demonstrated additive effects of ZL-2313 with osimertinib in preclinical models of tumor progression, reinforcing the clinical need addressed by the SYMPHONY study in first-line EGFR L858R+ NSCLC.

•ZL-1211 (claudin18.2, global rights): In April 2023, Zai Lab presented new data including a translational and biomarker data analysis from its internal oncology discovery program ZL-1211 at the 2023 AACR (Free AACR Whitepaper) Annual Meeting.
Autoimmune Disorders, Infectious Diseases and Neuroscience
•Sulbactam-Durlobactam (SUL-DUR, Asia Pacific rights): In April 2023, Zai Lab partner Entasis Therapeutics Inc. (Entasis), a wholly owned subsidiary of Innoviva, announced that the FDA’s Antimicrobial Drugs Advisory Committee (AMDAC) unanimously voted 12-0 in support of approval of its New Drug Application (NDA) for SUL-DUR based on a favorable benefit-risk assessment for the treatment of adults with hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia caused by susceptible strains of Acinetobacter baumannii-calcoaceticus complex (Acinetobacter). Zai Lab participated in the global Phase 3 registrational ATTACK trial in Greater China, and China’s National Medical Products Administration (NMPA) accepted the Company’s NDA in February 2023.
•KarXT (xanomeline-trospium, M1/M4-preferring muscarinic acetylcholine receptor): In March 2023, Zai Lab partner Karuna Therapeutics, Inc. (Karuna) announced positive results from the Phase 3 EMERGENT-3 trial of KarXT in schizophrenia. The trial met its primary endpoint, with KarXT demonstrating a statistically significant and clinically meaningful 8.4-point reduction in Positive and Negative Syndrome Scale (PANSS) total score compared to placebo (-20.6 KarXT vs. -12.2 placebo; p<0.0001) at Week 5 (Cohen’s d effect size of 0.60). Consistent with prior trials, KarXT demonstrated an early and sustained statistically significant reduction of symptoms from Week 2 (p<0.05) through the end of the trial as assessed by PANSS total score.
Corporate Updates
•Business development: In April 2023, Zai Lab entered into a strategic partnership and global license agreement with MediLink Therapeutics. Through this collaboration, the Company expanded its lung cancer franchise and global oncology pipeline with a next-generation DLL3 ADC Program, ZL-1310. DLL3 is an inhibitor of the Notch ligand that is overexpressed in small cell lung cancer and neuroendocrine tumors. ZL-1310 has demonstrated an encouraging pre-clinical profile. ZL-1310 is progressing to the clinical stage, and Zai Lab plans to focus on advancing its global development.
•Organizational update:
–Josh Smiley has been promoted to the role of President and Chief Operating Officer, effective April 1, 2023. Mr. Smiley joined the Company as our Chief Operating Officer in August 2022. He is responsible for our corporate strategy and for overseeing our commercial, manufacturing, business development, finance, human resources, information technology, and corporate affairs functions.
–Christine Chiou joined the Company in May 2023 as Senior Vice President, Head of Investor Relations. Ms. Chiou brings more than 20 years of industry experience across Investor Relations, equity research, and sales and market research. Prior to joining Zai Lab, she was at Incyte Corporation from November 2019 to April 2023 where she was most recently, the Head of Investor Relations and at Allergan (now part of AbbVie Inc.) from May 2018 to October 2019 where she was the Director of Investor Relations.
•2023 Investor Day: Zai Lab will host an Investor Day in New York on Tuesday, June 20, 2023.
Anticipated Major Milestones in 2023
Oncology
ZEJULA (niraparib, PARP)
•Zai Lab to present the final overall survival (OS) analysis of the Phase 3 NORA study in Chinese patients.
Tumor Treating Fields or TTFields
•Zai Lab partner NovoCure Limited (NovoCure) to present the results of the pivotal LUNAR clinical study in NSCLC for the first time at the 2023 ASCO (Free ASCO Whitepaper) Annual Meeting. The LUNAR data will be presented on Tuesday, June 6 at 11:09 a.m. CDT in Hall D1 as a late-breaking abstract during ASCO (Free ASCO Whitepaper)’s metastatic, non-small cell lung cancer session. Zai Lab participated in the study in Greater China.
•NovoCure to provide a topline data readout from the global pivotal INNOVATE-3 clinical study testing the efficacy of TTFields together with paclitaxel in platinum-resistant ovarian cancer in the second half of 2023.

TIVDAK (tisotumab vedotin, ADC)
•Seagen to provide a clinical data update for the Phase 1b/2 innovaTV 205 study in first-line+ r/m cervical cancer in the second half of 2023.
KRAZATI (adagrasib, KRASG12C)
•Zai Lab partner Mirati to provide a clinical data update for the global Phase 2 KRYSTAL-7 study of adagrasib in combination with pembrolizumab in first-line KRASG12C-mutated NSCLC in the second half of 2023. Zai Lab is participating in the study in Greater China.
•Mirati to provide update on multi-pronged development approach in first-line KRASG12C-mutated NSCLC in the second half of 2023.
•Mirati to submit a supplemental New Drug Application (sNDA) for Accelerated Approval to the FDA in third-line+ KRASG12C-mutated advanced colorectal cancer (CRC) by year-end 2023.
Bemarituzumab (FGFR2b)
•Zai Lab to join the global Phase 3 FORTITUDE-101 study in first-line gastric cancer in China in mid-2023.
•Zai Lab to join the global Phase 3 FORTITUDE-102 study in first-line gastric cancer in China.
Odronextamab (CD20xCD3)
•Zai Lab partner Regeneron Pharmaceuticals, Inc. (Regeneron) to initiate confirmatory studies in follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) including in earlier lines in the second quarter of 2023.
•Regeneron to submit a Biologics License Application (BLA) to the FDA for relapsed/refractory (R/R) DLBCL and R/R FL in the second half of 2023.
Repotrectinib (ROS1/TRK)
•Zai Lab to submit an NDA to the NMPA for ROS1+ advanced NSCLC.
MARGENZA (margetuximab, HER2)
•Potential China NDA approval by the NMPA in third-line+ metastatic HER2+ breast cancer.
ZL-2313 (BLU-945, EGFR)
•Zai Lab partner Blueprint to present updated results from the dose escalation of the Phase 1/2 SYMPHONY trial showing safety and tolerability of BLU-945 both as a monotherapy and in combination with osimertinib in late-line EGFR-driven NSCLC at the 2023 ASCO (Free ASCO Whitepaper) Annual Meeting.
•Blueprint to provide an initial clinical data update on the SYMPHONY trial expansion of ZL-2313 in combination with osimertinib in first-line EGFR L858R+ NSCLC in the second half of 2023.
ZL-1218 (CCR8, global rights):
•Zai Lab to initiate a global Phase 1 study.
Autoimmune Disorders, Infectious Disease and Neuroscience
VYVGART (efgartigimod, FcRn)
•Potential BLA approval and commercial launch by the NMPA for efgartigimod alfa injection for the treatment of adult patients with gMG in China.
•Potential BLA submission to the NMPA for SC efgartigimod for the treatment of adult patients with gMG in China in mid-2023.
•Zai Lab to join the global Phase 2/3 BALLAD study in adult patients with bullous pemphigoid in China.
4

•Potential BLA approval by the FDA for SC efgartigimod for gMG in the first half of 2023, with a Prescription Drug User Fee Act (PDUFA) date of June 20, 2023.
•Zai Lab partner argenx BV (argenx) to report topline data from the registrational ADHERE trial of SC efgartigimod for chronic inflammatory demyelinating polyneuropathy (CIDP) in July 2023. Zai Lab participated in the study in Greater China.
•argenx to report topline data from the registrational Phase 3 ADDRESS trial of SC efgartigimod in pemphigus and the registrational Phase 3 ADVANCE-SC trial of SC efgartigimod in immune thrombocytopenia (ITP) in the fourth quarter of 2023. Zai Lab participated in both studies in Greater China.
Sulbactam-Durlobactam (SUL-DUR, China and Asia Pacific rights)
•Potential FDA approval of the NDA for SUL-DUR, which was accepted for priority review with an action date of May 29, 2023.
KarXT (xanomeline-trospium, M1/M4-preferring muscarinic acetylcholine receptor)
•Zai Lab to initiate a bridging study for KarXT for the treatment of patients with schizophrenia in China in mid-2023.
•Zai Lab partner Karuna to submit an NDA to the FDA for KarXT for the treatment of patients with schizophrenia in the third quarter of 2023.
•Karuna to initiate the Phase 3 ADEPT-2 trial in Alzheimer’s disease psychosis in the second half of 2023. Zai Lab plans to participate in the study in Greater China.

First-Quarter 2023 Financial Results

•Product revenues were $62.8 million for the first quarter of 2023, compared to $46.1 million for the same period in 2022, representing a 36.2% y-o-y growth. Product revenue for the first quarter of 2023 was $42.7 million for ZEJULA, compared to $29.6 million for the same period in 2022, representing a 44.2% y-o-y growth; $13.3 million for Optune, compared to $12.8 million for the same period in 2022, representing a 4.3% y-o-y growth; $1.3 million for QINLOCK, compared to $3.0 million for the same period in 2022; and $5.5 million for NUZYRA, compared to $0.7 million for the same period in 2022

–Note that product revenue for the first quarter of 2023 included a negative $3.9 million adjustment to compensate distributors for sales of QINLOCK and NUZYRA at prices prior to the price reductions made in connection with their addition to the NRDL in the first quarter of 2023. Such sales rebates to distributors on previously purchased products are customary in our industry to compensate those distributors for the new NRDL selling price.
•Research and Development (R&D) expenses were $48.5 million for the first quarter of 2023, compared to $53.9 million for the same period in 2022. The decrease in R&D expenses was primarily due to cost-sharing compensation from collaboration partners related to our clinical trials, partially offset by higher payroll and payroll-related expenses from increased R&D headcount.
•Selling, General and Administrative expenses were $62.5 million for the first quarter of 2023, compared to $57.0 million for the same period in 2022. The increase was primarily due to higher professional service fees and in connection with sales of our products in mainland China and Hong Kong, and higher payroll and payroll-related expenses from increased commercial headcount.
•Net loss was $49.1 million for the first quarter of 2023, or a loss per share attributable to common stockholders of $0.05, compared to a net loss of $82.4 million for the same period in 2022, or a loss per share attributable to common stockholders of $0.09. The decrease in net loss was primarily due to product revenue growing faster than operating expenses, and an increase in non-operating income, including interest income and foreign currency gain.
•Cash and cash equivalents, short-term investments and restricted cash totaled $931.4 million as of March 31, 2023, compared to $1,009.3 million as of December 31, 2022.
Conference Call and Webcast Information
Zai Lab will host a live conference call and webcast tomorrow, May 10, 2023, at 8:00 a.m. ET. Listeners may access the live webcast by visiting the Company’s website at View Source Participants must register in advance of the conference call.

Details are as follows:
Registration Link: https://register.vevent.com/register/BI7faa33a643804925b414bbe98d0687b1
All participants must use the link provided above to complete the online registration process in advance of the conference call. Dial-in details will be in the confirmation email which the participant will receive upon registering.
A replay will be available shortly after the call and can be accessed by visiting the Company’s website.

On May 9, 2023 XOMA Corporation (NASDAQ: XOMA), the biotech royalty aggregator, reported its first quarter 2023 financial results and highlighted recent operational achievements as the Company accelerates XOMA’s differentiated biotech royalty and milestone acquisition strategy (Press release, Xoma, MAY 9, 2023, View Source [SID1234631303]).

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"We are increasing our efforts to be a provider of capital to emerging biotech companies, often enabling these companies to unlock value in the face of a challenging market backdrop for innovative, early stage companies," stated Owen Hughes, Executive Chairman of XOMA. "In the first quarter, the team acted rapidly and decisively to add a second cashflow-generating, long-duration asset to XOMA’s milestone and royalty portfolio. We will continue to reinvest our incoming cashflows and milestone payments to accelerate our royalty monetization strategy."

"The first five months of 2023 have demonstrated both the royalty potential within and the opportunities to grow our royalty and milestone aggregator business model. In February, we received a payment related to the commercial sales of Vabysmo (faricimab) during the second half of 2022. In March, we acquired the IXINITY [coagulation factor IX (recombinant)] commercial payment stream held by Aptevo and will begin recording those commercial payments in the second quarter of 2023," said Brad Sitko, Chief Investment Officer of XOMA. "The team and I are actively identifying additional royalty and milestone acquisition agreements that can deliver significant value to XOMA and our shareholders."

First Quarter 2023 Financial Results

XOMA recorded total revenues of $0.4 million for the first quarter of 2023, compared with $3.1 million in the first quarter of 2022. In the first quarter of 2022, XOMA recognized $2.0 million in revenue related to a milestone event under the Company’s license agreement with Rezolute and a $0.8 million milestone earned pursuant to its Takeda Collaboration Agreement. XOMA did not recognize milestone revenue during the three months ended March 31, 2023.

Research and development ("R&D") expenses were $54,000 and $56,000, respectively, for the first quarters of 2023 and 2022.

General and administrative ("G&A") expenses were $6.2 million for the first quarter of 2023, compared to $5.1 million for the first quarter of 2022. The increase of $1.1 million for the three months ended March 31, 2023, as compared to the corresponding period of 2022, was primarily due to a $0.6 million increase in stock-based compensation expense and a $0.3 million increase in consulting and legal costs.

In the first quarter of 2023, the Company reported arbitration settlement costs of $4.1 million, consisting of the costs incurred related to the arbitration proceeding settlement with one of its licensees.

In the first quarter of 2023, G&A expenses included $1.6 million in non-cash stock-based compensation expense, compared with $1.0 million in the first quarter of 2022. XOMA’s net cash used in operating activities during the first quarter of 2023 was $4.9 million, as compared with $1.0 million during the first quarter of 2022.

The Company reported total other income, net, of $0.4 million in the first quarter of 2023, as compared to total other expense, net, of $0.2 million in the corresponding period of 2022. The $0.6 million variation between the corresponding quarters reflects a $0.4 million increase in investment income and a $0.2 million change in fair value of equity securities XOMA holds in Rezolute, Inc.

Net loss for the first quarter of 2023 was $9.8 million, compared to a net loss of $2.3 million for the first quarter of 2022.

On March 31, 2023, XOMA had cash and cash equivalents of $44.3 million and no debt on its balance sheet. On December 31, 2022, XOMA had cash and cash equivalents of $57.8 million. On January 17, 2023, the Company paid cash dividends on the 8.625% Series A Cumulative Perpetual Preferred Stock (Nasdaq: XOMAP) equal to $0.53906 per share and cash dividends on the 8.375% Series B Cumulative Perpetual Preferred Stock (Nasdaq: XOMAO) equal to $0.52344 per depositary share. In February 2023, XOMA received a cash payment from Roche, representing the second commercial payment from XOMA’s 0.5% commercial interest in the sales of Vabysmo. This payment is reflected in the Company’s condensed consolidated balance sheet as of March 31, 2023, as a reduction of short-term royalty and commercial payment receivables.

On May 9, 2023 Xilio Therapeutics, Inc. (Nasdaq: XLO), a clinical-stage biotechnology company discovering and developing tumor-activated immuno-oncology therapies for people living with cancer, reported pipeline progress and business updates and reported financial results for the first quarter ended March 31, 2023 (Press release, Xilio Therapeutics, MAY 9, 2023, View Source [SID1234631302]).

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"In the first quarter, we continued to progress multiple clinical programs, notably with the recent initiation of our first Phase 2 clinical trial," said René Russo, Pharm.D., chief executive officer of Xilio. "The Phase 2 trial will assess the safety and efficacy of XTX202, our tumor-activated IL-2, in patients with advanced renal cell carcinoma and melanoma. To date, we have administered XTX202 in the outpatient setting at high dose levels and have not observed any of the severe systemic side effects commonly associated with recombinant IL-2. In addition, we plan to report preliminary data later this quarter from our Phase 1 clinical trial for XTX101, our tumor-activated, Fc-enhanced anti-CTLA-4."

Pipeline and Business Updates

XTX202: tumor-activated, engineered, beta-gamma biased IL-2

XTX202 is an investigational tumor-activated beta-gamma biased, engineered IL-2 molecule designed to potently stimulate CD8+ effector T cells and natural killer (NK) cells without concomitant stimulation of regulatory T cells when activated (unmasked) in the tumor microenvironment (TME). XTX202 is currently being evaluated in an ongoing Phase 1/2 clinical trial in patients with advanced solid tumors.

● Xilio recently initiated patient dosing at an initial dose of 1.4 mg/kg in a Phase 2 clinical trial evaluating XTX202 as a monotherapy in patients with unresectable or metastatic melanoma and metastatic renal cell carcinoma who have progressed on standard-of-care treatment.
● In addition, Xilio recently cleared the 1.4 mg/kg dose level (dose level five) in monotherapy dose-escalation (Part 1A) for the Phase 1 clinical trial and is currently dosing patients at the 2.8 mg/kg dose level (dose level six).
● A maximum tolerated dose has not yet been determined, and enrollment in Part 1A and Part 1B of the Phase 1 clinical trial is ongoing.
● Xilio anticipates reporting preliminary anti-tumor activity, safety, pharmacokinetic (PK) and pharmacodynamic (PD) data from the Phase 1/2 clinical trial in the third quarter of 2023. The company anticipates the reported data will include approximately 15-20 evaluable patients across a range of solid tumors treated at the 1 mg/kg dose or higher across all cohorts in the Phase 1/2 clinical trial.
XTX301: tumor-activated, engineered IL-12

XTX301 is an investigational tumor-activated, engineered IL-12 molecule designed to potently stimulate anti-tumor immunity and reprogram the TME of poorly immunogenic "cold" tumors towards an inflamed or "hot" state.

● Xilio has opened clinical trial sites and is actively screening patients for enrollment at a starting dose of 5.0 ug/kg (0.005 mg/kg) in monotherapy dose-escalation for its Phase 1 clinical trial evaluating the safety and tolerability of XTX301 in patients with advanced solid tumors.
● Xilio anticipates reporting preliminary safety data from the Phase 1 clinical trial into at least the third dose level in the fourth quarter of 2023.
XTX101: tumor-activated, Fc-enhanced anti-CTLA-4

XTX101, an investigational tumor-activated, Fc-enhanced, high affinity binding anti-CTLA-4, is currently being evaluated in monotherapy dose-expansion (Part 1B) of an ongoing Phase 1 clinical trial in patients with advanced solid tumors.

● Xilio reported the acceptance of an abstract highlighting preliminary Phase 1 data at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. Xilio plans to report additional preliminary Phase 1 safety, PK, PD, and anti-tumor activity data by the end of the second quarter of 2023.
● In addition, as previously announced, Xilio plans to continue to explore strategic opportunities to advance XTX101 with a partner beyond the current Phase 1 trial.
Upcoming Presentations and Accepted Abstracts

Xilio reported the acceptance of the following two abstracts at the 2023 ASCO (Free ASCO Whitepaper) Annual Meeting in Chicago, Illinois.

Xilio will present a trials-in-progress poster highlighting details of the Phase 1 clinical trial for XTX301:

● Presentation title: A first-in-human study of XTX301, a masked, tumor-activated interleukin-12 (IL-12), in patients with advanced solid tumors.
● Session date and time: June 3, 2023, 9:00 am to 12:00 pm EDT
● Abstract number: TPS2672
The following abstract highlighting preliminary safety, PK, and anti-tumor activity data from the Phase 1 clinical trial for XTX101 was accepted for inclusion in the 2023 ASCO (Free ASCO Whitepaper) Annual Meeting Proceedings, Journal of Clinical Oncology supplement:

● Presentation Title: Phase 1/2 study of XTX101, a masked, tumor-selective Fc-modified anti-CTLA-4, in patients with advanced solid tumors.
● Abstract number: e14685
First Quarter 2023 Financial Results

● Cash Position: Cash and cash equivalents were $93.3 million as of March 31, 2023, compared to $120.4 million as of December 31, 2022.
● Research & Development (R&D) Expenses: R&D expenses were $16.1 million for the quarter ended March 31, 2023, compared to $14.9 million for the quarter ended March 31, 2022. The increase was primarily driven by increased clinical development activities for XTX202, increased clinical development and manufacturing activities for XTX301, increased personnel-related costs, and increased costs related to the company’s earlier-stage programs. These increases were partially
offset by decreases in manufacturing activities for XTX202, preclinical development activities for XTX301 and clinical development activities for XTX101.
● General & Administrative (G&A) Expenses: G&A expenses were $7.4 million for the quarter ended March 31, 2023, compared to $6.3 million for the quarter ended and March 31, 2022. The increase was primarily driven by increased personnel-related costs and an increase in professional and consulting fees.
● Net Loss: Net loss was $22.6 million for the quarter ended March 31, 2023, compared to $21.4 million for the quarter ended March 31, 2022.
Financial Guidance

Xilio anticipates that its existing cash and cash equivalents will be sufficient to fund its operating expenses and capital expenditure requirements into the end of the second quarter of 2024.

About XTX202 (IL-2) and the Phase 1/2 Clinical Trial

XTX202 is an investigational tumor-activated beta-gamma biased, engineered IL-2 molecule designed to potently stimulate CD8+ effector T cells and natural killer (NK) cells without concomitant stimulation of regulatory T cells when activated (unmasked) in the tumor microenvironment (TME). The Phase 1 clinical trial for XTX202 is a first-in-human, multi-center, open-label trial designed to evaluate the safety and tolerability of XTX202 as a monotherapy in patients with advanced solid tumors. The Phase 2 clinical trial for XTX202 is a multi-center, open-label trial designed to evaluate the safety and efficacy of XTX202 as a monotherapy in patients with unresectable or metastatic melanoma and metastatic renal cell carcinoma who have progressed on standard-of-care treatment. Please refer to NCT05052268 on www.clinicaltrials.gov for additional details.

About XTX301 (IL-12) and the Phase 1 Clinical Trial

XTX301 is an investigational tumor-activated, engineered IL-12 molecule designed to potently stimulate anti-tumor immunity and reprogram the tumor microenvironment (TME) of poorly immunogenic "cold" tumors towards an inflamed or "hot" state. The Phase 1 clinical trial for XTX301 is a first-in-human, multi-center, open-label trial designed to evaluate the safety and tolerability of XTX301 as a monotherapy in patients with advanced solid tumors. Please refer to NCT05684965 on www.clinicaltrials.gov for additional details.

About XTX101 (anti-CTLA-4) and the Phase 1 Clinical Trial

XTX101 is an investigational tumor-activated, Fc-enhanced, high affinity binding anti-CTLA-4 monoclonal antibody designed to deplete regulatory T cells when activated (unmasked) in the tumor microenvironment (TME). The Phase 1 clinical trial is a first-in-human, multi-center, open-label trial designed to evaluate the safety and tolerability of XTX101 for the treatment of adult patients with advanced solid tumors. Please refer to NCT04896697 on www.clinicaltrials.gov for additional details.