On August 9, 2021 Intra-Cellular Therapies, Inc. (Nasdaq: ITCI), a biopharmaceutical company focused on the development and commercialization of therapeutics for central nervous system (CNS) disorders, reported its financial results for the second quarter ended June 30, 2021 and provided a corporate update (Press release, Intra-Cellular Therapies, AUG 9, 2021, View Source [SID1234586177]).

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"We are pleased with our strong results in the second quarter. Our sNDAs for bipolar depression are under review by the FDA and our CAPLYTA strategy continues to make substantial progress with our commercialization in schizophrenia, along with our preparations for a potential label expansion into bipolar depression. We have initiated patient enrollment in our Phase 3 program in MDD and continue our programs studying other depressive disorders," said Dr. Sharon Mates, Chairman and CEO of Intra-Cellular Therapies.

Second Quarter Financial Highlights

Total revenues were $20.0 million for the second quarter of 2021, compared to $1.9 million of total revenues for the second quarter of 2020. Net product revenues of CAPLYTA were $19.0 million for the second quarter of 2021, compared to $1.9 million in net product revenues of CAPLYTA for the same period in 2020. Net product revenues of CAPLYTA increased 22% from $15.6 million in the prior quarter.
Cost of product sales were $2.0 million in the second quarter of 2021 compared to $0.1 million for the second quarter of 2020.
Research and development (R&D) expenses for the second quarter of 2021 were $17.3 million, compared to $25.2 million for the second quarter of 2020. This decrease is due primarily to a decrease in lumateperone clinical trial costs.
Selling, general and administrative (SG&A) expenses were $69.9 million for the second quarter of 2021, compared to $41.4 million for the same period in 2020. This increase is primarily due to an increase in commercialization and marketing costs.
Net loss for the second quarter of 2021 was $68.7 million compared to a net loss of $63.7 million for the second quarter of 2020.
Cash, cash equivalents, restricted cash and investment securities totaled $556.2 million at June 30, 2021, compared to $658.8 million at December 31, 2020.
COMMERCIAL HIGHLIGHTS

Our hybrid commercialization model and our digital marketing initiatives continued to deliver consistent revenue and prescription growth despite COVID-19 disruptions.
Second quarter CAPLYTA results reflect continued prescription growth, increasing total prescriptions by 22% versus the first quarter of 2021.
CAPLYTA market access coverage is strong with greater than 95% of covered lives in both Medicare Part D and State Medicaid, the major payer channels in schizophrenia. Our LytaLink program continues to be highly competitive and effective in supporting prescribing physicians and eligible patients’ access to CAPLYTA.
Our bipolar depression launch preparations are on track.
CLINICAL HIGHLIGHTS

Lumateperone:

Bipolar Depression Program: The lumateperone sNDAs for the treatment of depressive episodes associated with bipolar I or II disorder (bipolar depression) as monotherapy and as adjunctive therapy with lithium or valproate are under review by the U.S. Food and Drug Administration (FDA). The Prescription Drug User Fee Act (PDUFA) target action date is December 17, 2021 for these applications.
Adjunctive MDD program: Patient enrollment has commenced for Study ‘501, our Phase 3 clinical trial evaluating lumateperone 42 mg as an adjunctive therapy to antidepressants for the treatment of MDD. Patient enrollment in a second Phase 3 trial, Study ‘502, is anticipated to begin shortly.
Mixed Features program: Clinical conduct continues in Study ‘403 evaluating lumateperone 42 mg in patients with MDD and in patients with bipolar depression who exhibit mixed features.
Lumateperone Long Acting Injectable (LLAI) formulation: Study ITI-007-025, a Phase 1 single ascending dose study of LLAI, a formulation designed to be administered subcutaneously and to maintain therapeutic levels of lumateperone for at least one month, is ongoing. Initial results from this study are anticipated in the second half of 2021.
Presentations: In the second quarter of 2021, presented at the American Psychiatric Association (APA) Meeting, the International Conference for Bipolar Disorders (ISBD) Annual Meeting, and the American Society of Clinical Psychopharmacology. The presentations included results from Study ‘402, a Phase 3 clinical trial evaluating lumateperone as adjunctive therapy in bipolar depression, analyses from Study ‘404 describing the efficacy results of patients with bipolar depression who exhibit mixed features, and the overall safety and tolerability profile of the bipolar depression monotherapy program. We also presented analyses from Study ‘303, our long-term safety schizophrenia study, evaluating the antidepressant effects of CAPLYTA in patients with schizophrenia with co-morbid depression.
Other Programs:

ITI-1284 program: We plan to initiate our program for the development of ITI-1284-ODT-SL for the treatment of behavioral disturbances in dementia in the second half of 2021, and plan additional studies in dementia-related psychosis and certain depressive disorders in the elderly in 2022.
Phosphodiesterase type I inhibitor (PDE1) program: Our PDE1 inhibitor program is focused on investigating the therapeutic potential of this mechanism of action across a variety of diseases, including neurological and cardiovascular diseases, as well as cancer.
A Phase 2 study evaluating lenrispodun (ITI-214) in Parkinson’s disease is expected to commence in the second half of 2021.
Presented preclinical data describing the antitumor effects of PDE1 inhibitors when administered in conjunction with checkpoint inhibitor immunotherapy at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting. We are currently evaluating our PDE1 inhibitors in other cancer models and developing potential biomarkers that may assist in the translation of these data to the treatment of human cancers.
ITI-333 program in opioid use disorder: Study ITI-333-001, a Phase 1 single ascending dose study evaluating the safety, tolerability and pharmacokinetics of ITI-333 in healthy volunteers, is ongoing. Results from this study are anticipated in the second half of 2021.
R&D day: The Company plans to host a virtual research and development (R&D) day focusing on our key pipeline programs later this year.
Conference Call and Webcast Details

The Company will host a live conference call and webcast today at 8:30 AM Eastern Time to discuss the Company’s financial results and provide a corporate update. The live webcast and subsequent replay may be accessed by visiting the Company’s website at www.intracellulartherapies.com. Please connect to the Company’s website at least 5-10 minutes prior to the live webcast to ensure adequate time for any necessary software download. Alternatively, please call 1-(844) 835-6563 (U.S.) or 1-(970) 315-3916 (international) to listen to the live conference call. The conference ID number for the live call is 8494665. Please dial in approximately 10 minutes prior to the call.

CAPLYTA (lumateperone) is indicated for the treatment of schizophrenia in adults. CAPLYTA is available in 42 mg capsules.

Important Safety Information

Boxed Warning: Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. CAPLYTA is not approved for the treatment of patients with dementia-related psychosis.

Contraindications: CAPLYTA is contraindicated in patients with known hypersensitivity to lumateperone or any components of CAPLYTA. Reactions have included pruritus, rash (e.g., allergic dermatitis, papular rash, and generalized rash), and urticaria.

Warnings & Precautions: Antipsychotic drugs have been reported to cause:

Cerebrovascular Adverse Reactions in Elderly Patients with Dementia-Related Psychosis, including stroke and transient ischemic attack. See Boxed Warning above.
Neuroleptic Malignant Syndrome (NMS), which is a potentially fatal reaction. Signs and symptoms include: high fever, stiff muscles, confusion, changes in breathing, heart rate, and blood pressure, elevated creatinine phosphokinase, myoglobinuria (and/or rhabdomyolysis), and acute renal failure. Patients who experience signs and symptoms of NMS should immediately contact their doctor or go to the emergency room.
Tardive Dyskinesia, a syndrome of uncontrolled body movements in the face, tongue, or other body parts, which may increase with duration of treatment and total cumulative dose. TD may not go away, even if CAPLYTA is discontinued. It can also occur after CAPLYTA is discontinued.
Metabolic Changes, including hyperglycemia, diabetes mellitus, dyslipidemia, and weight gain. Hyperglycemia, in some cases extreme and associated with ketoacidosis, hyperosmolar coma or death, has been reported in patients treated with antipsychotics. Measure weight and assess fasting plasma glucose and lipids when initiating CAPLYTA and monitor periodically during long-term treatment.
Leukopenia, Neutropenia, and Agranulocytosis (including fatal cases). Complete blood counts should be performed in patients with pre-existing low white blood cell count (WBC) or history of leukopenia or neutropenia. CAPLYTA should be discontinued if clinically significant decline in WBC occurs in absence of other causative factors.
Decreased Blood Pressure & Dizziness. Patients may feel lightheaded, dizzy or faint when they rise too quickly from a sitting or lying position (orthostatic hypotension). Heart rate and blood pressure should be monitored and patients should be warned with known cardiovascular or cerebrovascular disease. Orthostatic vital signs should be monitored in patients who are vulnerable to hypotension.
Falls. CAPLYTA may cause sleepiness or dizziness and can slow thinking and motor skills, which may lead to falls and, consequently, fractures and other injuries. Patients should be assessed for risk when using CAPLYTA.
Seizures. CAPLYTA should be used cautiously in patients with a history of seizures or with conditions that lower seizure threshold.
Sleepiness and Trouble Concentrating. Patients should use caution when operating machinery or motor vehicles until they know how CAPLYTA affects them.
Body Temperature Dysregulation. CAPLYTA should be used with caution in patients who may experience conditions that may increase core body temperature such as strenuous exercise, extreme heat, dehydration, or concomitant anticholinergics.
Dysphagia. CAPLYTA should be used with caution in patients at risk for aspiration.
Drug Interactions: CAPLYTA should not be used with CYP3A4 inducers, moderate or strong CYP3A4 inhibitors and UGT inhibitors.

Special Populations: Newborn infants exposed to antipsychotic drugs during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery. Breastfeeding is not recommended. Use of CAPLYTA should be avoided in patients with moderate or severe liver problems.

Adverse Reactions: The most common adverse reactions in clinical trials with CAPLYTA vs. placebo were somnolence/sedation (24% vs. 10%) and dry mouth (6% vs. 2%).
Please click here to see full Prescribing Information including Boxed Warning.

About CAPLYTA (lumateperone)

CAPLYTA 42mg/day is an oral, once daily atypical antipsychotic approved for the treatment of schizophrenia of adults. While the mechanism of action of CAPLYTA in the treatment of schizophrenia is unknown, the efficacy of CAPLYTA could be mediated through a combination of antagonist activity at central serotonin 5-HT2A receptors and postsynaptic antagonist activity at central dopamine D2 receptors.

Lumateperone is being investigated for the treatment of bipolar depression, depression and other neuropsychiatric and neurological disorders. CAPLYTA is not FDA approved for these disorders.

On August 9, 2021 Race Oncology Limited ("Race") reported that the first patient has been dosed in the Phase 1b/2 trial in relapsed/refractory Acute Myeloid Leukaemia (ASX Announcement: 22 June 2021) (Press release, Race Oncology, AUG 9, 2021, View Source [SID1234591494]).

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This investigator-led trial supervised by Professor Arnon Nagler will use Zantrene (bisantrene dihydrochloride) in a novel three drug combination which has demonstrated compelling efficacy in pre-clinical studies (ASX Announcement: 10 May 2021). Prof Nagler was the Principal Investigator of the Phase 2 investigator-initiated trial where Zantrene was used as a single agent in R/R AML patients and reported an impressive 40% clinical response rate (ASX Announcement: 16 June 2020).

"We are delighted to see the start of this important clinical project which uses a novel combination approach for relapsed or refractory Acute Myeloid Leukaemia. This study is also an important step in our journey towards approval of Zantrene in this area of high unmet medical need."

Race CMO Dr David Fuller
The trial will run in parallel with a separate Australian Phase 2 trial in patients with extramedullary AML (ASX Announcement: 2 June 2021).

Both trials are key components of Race’s Three Pillar strategy.

Even when CR is achieved through intense chemotherapy, approximately half of the younger and 80% of the older patients, relapse. In both clinical situations, refractory and/or relapsed AML, active disease remains a major therapeutic challenge despite recent advances in the clinic.

"This study led by Professor Nagler who has good experience with Zantrene, supports the building of additional data in AML in line with our Three pillar strategy plan. We hope to see improved patient outcomes in what has been historically a difficult to treat disease. We plan on using our trademarked name, Zantrene, in referring to bisantrene dihydrochloride. It’s one of our registered trademarks and its protection is enhanced by its ongoing and appropriate use."

Race CEO & MD Phillip Lynch
Relapsed or Refractory Acute Myeloid Leukemia
Primary refractory or relapsed Acute Myeloid Leukemia is associated with poor prognosis and remains a serious therapeutic challenge. Primary refractory AML is defined by the absence of complete remission (CR), manifested by blast count of ≥5% in bone marrow after one or two cycles of intense induction chemotherapy.

Up to 30% of adults with newly diagnosed AML fail to achieve CR after two courses of intensive chemotherapy.

Clinical Trial Design
The trial is an open-label, Phase 1b/2 study of intravenous FluCloZan (Fludarabine, Clofarabine, Zantrene) in cohorts of up to 12 adult patients with R/R AML with a Phase 1b dose escalation stage to establish the maximum tolerated dose (MTD) or recommended Phase 2 dose of the combined FluCloZan regimen, followed by a Phase 2 expansion stage to determine efficacy and confirm safety of FluCloZan at the recommended Phase 2 dose in up to 17 patients.

Phase 1b, Dose-Escalation (Lead-in Stage)
A two-cohort dose escalation schema using a standard 3 + 3 design will be employed.

Cohort 1 will enroll three patients to receive the FluCloZan regimen for four consecutive days. If no dose limiting toxicities (DLTs) have occurred in the first three patients by day 30 of their first cycle of treatment, then Cohort 2 will receive the treatment for five days (with the extra day representing dose escalation).

Phase 2, Expansion (Efficacy Stage)
Up to 17 patients will be enrolled into a Phase 2 expansion efficacy cohort using a 2-stage Simon design. Initially, 9 patients will be enrolled and treated with the recommended Phase 2 dose of FluCloZan as determined in the Phase 1b part of the study. If there are no patient responses in the first nine subjects according to the response criteria outlined in the European Leukemia Net (ELN) guidelines, the study will be terminated for futility. If at least one patient shows a response, eight more patients will be enrolled and treated. If three or more of the patients treated in Stage 2 respond, the null hypothesis of treatment futility can be rejected.

Efficacy assessments will be based on bone marrow examination at a minimum of two time points on Day 21 and on Day 30. A further bone marrow examination may be performed on Day 42 at the investigator’s discretion, based on patient’s disease and performance status and/or on peripheral blood hematology results during the treatment course and between Day 21 to 42.

Treatment will be terminated upon any sign of progressive/recurrent disease and/or referral to pre-transplant conditioning therapy for (allogeneic) stem cell transplantation.

Patients who do not progress or experience any DLTs may receive a second course of treatment for the same duration as in their first cycle.

All patients will be actively followed-up every three months for a further 12 months following completion treatment for disease free survival (DFS) and overall survival (OS).

Indicative Costs and Timelines
The trial is expected to take 36 to 40 months to complete with full patient recruitment over approximately 18 months. Given the trial is open-label, Race expects that data will be reported at interim points throughout the trial.

Race will pay Chaim Sheba a total fee of USD $668,739 over the study’s life. Payments will be made to Chaim Sheba upon reaching key milestones and the total trial cost will depend on the number of patients recruited and other operational variables.

Clinical Trial Summary
Study Title An Open-label, Phase Ib/II, Two-stage, Study of Zantrene (Bisantrene) in combination with Fludarabine and Clofarabine as Salvage Therapy for Adult Patients with Relapsed or Refractory Acute Myeloid Leukaemia (AML)
Registration NCT04989335
Phase of Development Phase 1b/2
Active Ingredient Bisantrene dihydrochloride, Fludarabine, Clofarabine (FluCloZan)
Study Description Phase 1b/2 study of FluCloZan, IV, in cohorts of adult patients with R/R AML using a 2-stage design: a Phase 1b lead-in dose escalation stage to establish the MTD or RP2D of FluCloZan and a Phase 2 expansion stage to determine efficacy and confirm safety of the FluCloZan regimen at the RP2D.
Principal Investigator Professor Arnon Nagler
Sponsor Race Oncology
Indication/population Adult men and women 18 to 65 years of age with relapsed and/ or refractory Acute Myeloid Leukemia (R/R AML) presenting with non-CNS extramedullary disease.
Number of Subjects Phase 1b: up to 12 patients Phase 2: up to 17 patients in the expansion phase
Study Period 36 – 40 months
Study Design A two-cohort dose escalation schema using a standard 3 + 3 design will be employed followed by an expansion phase at the RP2D. As the patient population is considered relapsed and/or refractory to existing treatments, a comparator arm will not be used.
Statistical methods Simon 2 stage design
End Points Primary
Phase 1b Dose Escalation: number of subjects experiencing a DLT in each cohort Phase 2 Expansion: Overall Response Rate (ORR) defined as the proportion of subjects with CR and CRi between Day 30 to Day 42 Secondary: Transplant/allo-HSCT rates (for transplant/allo-HSCT-eligible subjects); Combined CR and CRi and PR response rate; Morphologic leukemia-free state (MLFS); Partial remission (PR); Stable disease (SD); Progressive disease (PD); Relapse; Disease free survival (DFS); Overall survival (OS); Time to next treatment (for transplant/allo-HSCT-ineligible subjects)
Participating Centres 1 Chaim Sheba Medical Center, Tel Hashomer, Israel
Dates First patient August 6, 2021; Last patient (anticipated): Q3 CY2023

On August 9, 2021 Aravive Inc. (Nasdaq: ARAV), a clinical-stage oncology company developing innovative therapeutics to treat life-threatening diseases, reported the Company has dosed the first patient in the Phase 1b portion of its Phase 1b/2 trial of AVB-500 in combination with gemcitabine and nab-paclitaxel as a first-line treatment in patients with advanced or metastatic pancreatic adenocarcinoma (Press release, Aravive, AUG 9, 2021, View Source [SID1234594062]). The Phase 1b portion of the clinical trial will evaluate safety, tolerability, pharmacokinetics, pharmacodynamics, and clinical activity of AVB-500 in combination with gemcitabine and nab-paclitaxel.

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"We are pleased with the quick advancement of AVB-500 with the first patient dosed in our Phase 1b/2 pancreatic adenocarcinoma trial. This clinical trial addresses a very high unmet medical need in one of the most difficult-to-treat cancers with a high mortality rate," said Gail McIntyre, Ph.D., DABT, Chief Executive Officer of Aravive. "We continue to expand the development of AVB-500, as the Company now has three ongoing clinical trials of AVB-500. In addition to the pancreatic adenocarcinoma clinical trial, AVB-500 is currently being investigated in a Phase 3 clinical trial for platinum resistant ovarian cancer and a Phase 1b/2 clinical trial for clear cell renal cell carcinoma."

The Phase 1b/2 clinical trial is designed to evaluate AVB-500 as a first-line therapy in combination with gemcitabine and nab-paclitaxel (Abraxane) in patients with advanced or metastatic pancreatic adenocarcinoma eligible to receive gemcitabine and nab-paclitaxel combination therapy. The Phase 1b portion of the clinical trial will evaluate safety, tolerability, pharmacokinetics, pharmacodynamics, and clinical activity in approximately 20 patients dosed with 15 mg/kg of AVB-500 in combination with gemcitabine and nab-paclitaxel. The randomized, controlled Phase 2 portion of the clinical trial is designed to evaluate approximately 60 patients dosed with 15 mg/kg of AVB-500 as a first-line therapy in combination with gemcitabine and nab-paclitaxel versus gemcitabine and nab-paclitaxel alone. The primary endpoint of the Phase 2 portion of the trial is progression-free survival. The secondary endpoints are objective response rate, duration of response, clinical benefit rate, safety and overall survival, and the exploratory endpoints are pharmacokinetics and pharmacodynamics. The Phase 1b/2 trial is listed on clinicaltrials.gov NCT04983407.

About Pancreatic Cancer
Pancreatic cancer is the seventh leading cause of cancer death worldwide. There were approximately 495,800 new cases of pancreatic cancer and 466,000 deaths from the disease worldwide in 2020. It is estimated that there will be approximately 60,400 new cases of pancreatic cancer and 48,200 deaths from the disease in the U.S. in 2021. Pancreatic cancer typically has a poor prognosis, and the five-year survival rate is approximately 11%. Pancreatic adenocarcinoma is the most common type of pancreatic cancer, and there is a clear, high, unmet medical need to improve patient survival with new effective treatments that are safe and well-tolerated. Pancreatic cancer is projected to become the third leading cause of cancer death worldwide by 2025 and the second leading cause of cancer death in the U.S. by 2030.

About AVB-500
AVB-500 is a therapeutic recombinant fusion protein that has been shown to neutralize GAS6 activity by binding to GAS6 with very high affinity in preclinical models. In doing so, AVB-500 selectively inhibits the GAS6-AXL signaling pathway, which is upregulated in multiple cancer types including ovarian, renal and pancreatic cancer. In preclinical studies, GAS6-AXL inhibition has shown anti-tumor activity in combination with a variety of anticancer therapies, including radiation therapy, immuno-oncology agents, and chemotherapeutic drugs that affect DNA replication and repair. Increased expression of AXL and GAS6 in tumors has been correlated with poor prognosis and decreased survival and has been implicated in therapeutic resistance to conventional chemotherapeutics and targeted therapies. AVB-500 is currently being evaluated in multiple clinical trials and has been granted Fast Track Designation by the U.S. Food and Drug Administration in platinum resistant recurrent ovarian cancer. Analysis of all safety data to date showed that AVB-500 has been generally well tolerated with no dose-limiting toxicities or unexpected safety signals.

On August 9, 2021 Navrogen, Inc., a privately held preclinical biotechnology company, reported that it has raised $3.0M from an equity financing to support its Humoral Immuno-Oncology (HIO) discovery platform and preclinical therapeutic pipeline activities (Press release, Navrogen, AUG 9, 2021, View Source [SID1234586102]). HIO is a process by which tumors produce factors that suppress a patient’s humoral immune response against malignant tissues. The major use of proceeds will focus on advancing the company’s lead HIO-refractory, anti-mesothelin NAV-001 antibody drug conjugate program and its NK cell activator platforms that specifically address HIO suppressed cancers and immune-mediated diseases. The financing was led by Tellus BioVentures along with existing investors. As part of the financing, Lonnie Moulder, Managing Member of Tellus, and Allan Bedwick, will join the Navrogen Board of Directors.

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"We are pleased to have Tellus BioVentures lead this round of funding as we take steps to further validate and advance our pipeline agents towards clinical development," stated Nicholas Nicolaides, Ph.D., Chief Executive Officer at Navrogen. "With Tellus, we gain additional access to professionals with deep biopharmaceutical operational and drug development experience that coupled with our extensive internal expertise will strengthen the pursuit of our value-creating objectives to deliver innovative medicines to patients with HIO-positive cancers and other immune-related disorders."

Lonnie Moulder, Managing Member of Tellus BioVentures, added, "We are thrilled to support Navrogen and its accomplished founding team in their efforts to achieve their platform and pipeline goals. Navrogen has discovered a unique translational approach for developing a new class of compounds to address immune-mediated diseases, including various cancer types".

On August 9, 2021 Zai Lab Limited (NASDAQ: ZLAB; HKEX: 9688), an innovative commercial-stage biopharmaceutical company, reported financial results for the second quarter of 2021, along with recent product highlights and corporate updates (Press release, Zai Laboratory, AUG 9, 2021, View Source [SID1234586117]).

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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

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"Consistent with our past track record, Zai Lab continued to execute with speed and quality across the organization during the second quarter," said Dr. Samantha Du, Founder, Chairperson and Chief Executive Officer of Zai Lab. "We successfully launched QINLOCK, the first product in what we hope will become a world-class gastric cancer franchise, in China; generated strong revenue growth from ZEJULA and Optune; and entered into strategic collaborations with Mirati, MacroGenics and Schrödinger to further strengthen our disease strongholds in oncology and our global pipeline.

"We anticipate achieving multiple regulatory milestones across our product pipeline throughout 2021, including the potential approval of NUZYRA for community-acquired bacterial pneumonia (CABP) and acute bacterial skin and skin structure infections (ABSSSI) by the NMPA. We also continue to make progress in numerous regulatory activities, and we anticipate a discussion with the NMPA in the near future on the filing strategy for efgartigimod. In addition, we anticipate many important data readouts and updates in the remainder of this year, including for Tumor Treating Fields in ovarian cancer, for QINLOCK in second-line GIST, for margetuximab in gastric cancer, for CLN-081 in non-small cell lung cancer (NSCLC), for TPX-0022 in NSCLC and gastric cancer, for adagrasib in NSCLC and colorectal cancer, and for other product candidates in our global pipeline.

"We are focused more than ever on our mission to build a leading global biopharmaceutical company addressing the unmet medical needs of patients in China and around the world," Dr. Du concluded.

Recent Product Highlights and Anticipated Milestones

Oncology

ZEJULA (niraparib)

ZEJULA is an oral, once-daily small-molecule poly ADP-ribose polymerase (PARP) 1/2 inhibitor. It is the only once-daily PARP inhibitor approved in the United States, the European Union and mainland China (hereinafter, "China") as a monotherapy maintenance treatment for patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to first-line platinum-based chemotherapy, regardless of their biomarker status.

Recent Product Highlight

Zai Lab has made significant progress in recent months in the number of hospitals that list ZEJULA as an approved medicine. From the date of National Reimbursement Drug List (NRDL) implementation on March 1, 2021 to June 30, 2021, the number of hospitals listing ZEJULA has increased sevenfold to more than 800.
Anticipated 2021 Zai Milestones

Complete enrollment of the Phase 1b study of ZEJULA in combination with tebotelimab in gastric cancer.

Announce topline results of the Phase 3 PRIME study of ZEJULA in Chinese patients with first-line ovarian cancer.

Seek NRDL inclusion for a first-line ovarian cancer indication.

Continue to explore additional indications and combination opportunities.
Tumor Treating Fields

Tumor Treating Fields (TTFields) are electric fields tuned to specific frequencies to disrupt cell division.

Recent Product Highlights

In July 2021, Zai Lab partner Novocure announced the final results from its Phase 2 pilot HEPANOVA trial in liver cancer testing the safety and efficacy of TTFields together with sorafenib for the treatment of advanced hepatocellular cancer. In 21 evaluable patients, HEPANOVA showed a 76% disease control rate , 9.5% objective response rate and 5.8 months of progression free survival in a patient population with poor prognosis and limited exposure to study treatments. In patients who completed at least 12 weeks (n=11) of TTFields treatment, the disease control rate was 91% with an 18% objective response rate. Novocure is actively designing a Phase 3 pivotal trial that contemplates TTFields together with the current standard of care, including immunotherapy.

In May 2021, Zai Lab partner Novocure announced that the U.S. Food and Drug Administration (FDA) approved the Investigational Device Exemption (IDE) supplement incorporating the independent data monitoring committee’s recommended protocol changes for its Phase 3 pivotal LUNAR trial in NSCLC, reducing the enrollment requirement to 276 patients with 12 months follow-up following the enrollment of the last patient. Novocure now anticipates last patient enrollment in the LUNAR trial in the fourth quarter of 2021, with final data available in 2022.

In April 2021, 26 presentations on TTFields at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2021 suggested the broad applicability of TTFields.

In April and May 2021, Zai Lab initiated the pivotal Phase 3 LUNAR trial in NSCLC and the pivotal Phase 3 METIS trial in brain metastases from NSCLC, respectively, in Greater China.

Zai Lab held extensive campaigns for Optune in Standardized Multi-Department Treatment programs in hospitals.

Optune has been listed in 14 regional customized commercial health insurance plans offered by provincial or municipal governments (or "supplemental insurance plans") since its commercial launch in China in the third quarter of 2020.
Anticipated 2021 Zai Milestones

Submit a Marketing Authorization Application (MAA) for malignant pleural mesothelioma.

Join the global Phase 3 pivotal PANOVA-3 trial for TTFields in locally advanced pancreatic cancer and the Phase 3 pivotal INNOVATE-3 trial for TTFields in recurrent ovarian cancer.

Complete enrollment of the Phase 2 pilot trial in first-line gastric adenocarcinoma.
Anticipated 2021 Partner Milestone

Complete the interim analysis of the Phase 3 pivotal INNOVATE-3 trial for TTFields in recurrent ovarian cancer.
QINLOCK (ripretinib)

QINLOCK is a switch-control tyrosine kinase inhibitor engineered to broadly inhibit KIT- and PDGFRα-mutated kinases. It is the only therapeutic approved in the United States and China for advanced gastrointestinal stromal tumors (GIST) patients who have received prior treatment with three or more kinase inhibitors in the all-comer setting.

Recent Product Highlights

In July 2021, QINLOCK was included in the Chinese Society of Clinical Oncology (CSCO) Guidelines for Diagnosis and Treatment of Gastrointestinal Stromal Tumors 2021 for second-line treatments for advanced GIST patients.

In June 2021, Deciphera presented the intra-patient dose escalation data from the INVICTUS Phase 3 study of QINLOCK in GIST patients. The exploratory analysis showed that dose escalation to QINLOCK 150 mg BID after disease progression on QINLOCK 150 mg QD may be able to offer substantial additional clinical benefit with a tolerable safety profile.

In May 2021, Zai Lab launched QINLOCK in China, our third innovative oncology product launch in China in the last 16 months. Zai Lab has held multiple national launch events for QINLOCK across China since its approval. QINLOCK is listed in two supplemental insurance plans.

Anticipated 2021 Partner Milestones

Obtain topline data from the INTRIGUE Phase 3 study of QINLOCK in patients with second-line GIST in the fourth quarter.

Initiate a Phase 1b/2 study in combination with the MEK inhibitor binimetinib in imatinib-refractory or -intolerant GIST patients.
Adagrasib

Adagrasib is a highly selective and potent oral small-molecule inhibitor of KRASG12C for treating KRAS-G12C-mutated NSCLC, colorectal cancer (CRC), pancreatic cancer and other solid tumors.

Recent Product Highlight

In June 2021, Zai Lab partner Mirati announced that the FDA granted Breakthrough Therapy Designation to adagrasib for the potential treatment of NSCLC patients who harbor the KRASG12C mutation following prior systemic therapy.
Anticipated 2021 Partner Milestones

Mirati plans to present updated NSCLC data in the second half of 2021 and submit an NDA in the United States for adagrasib in the fourth quarter of 2021 for the potential treatment of patients with NSCLC who harbor the KRASG12C mutation following prior systemic therapy.

Mirati plans to present new CRC data from the Phase 1/2 KRYSTAL-01 study evaluating adagrasib in combination with cetuximab (ERBITUX) in second-line patients with a KRASG12C mutation and as a monotherapy in patients who have received three or more lines of therapy.
Odronextamab

Odronextamab is a bispecific monoclonal antibody designed to trigger tumor killing by linking and activating a cytotoxic T-cell (binding to CD3) to a lymphoma cell (binding to CD20).

Recent Product Highlight

In May 2021, Zai Lab partner Regeneron resumed the enrollment of patients with follicular lymphoma and diffuse large B-cell lymphoma in the potentially pivotal Phase 2 program.
Anticipated 2021 Zai Milestone

Enroll the first patient in Greater China in the global, potentially pivotal Phase 2 program.
Anticipated 2021 Partner Milestone

Initiate development of a subcutaneous formulation.
Repotrectinib

Repotrectinib is a next-generation tyrosine kinase inhibitor (TKI) designed to effectively target ROS1 and TRK A/B/C, with the potential to treat TKI-naïve or TKI-pretreated patients.

Recent Product Highlight

In May 2021, Zai Lab enrolled the first patient in Greater China in the global registrational Phase 2 TRIDENT-1 study for both the ROS1+ advanced NSCLC and the NTRK+ advanced solid tumor cohorts.
Anticipated 2021 Partner Milestones

Reach enrollment of 50 patients from both the Phase 1 and Phase 2 portions of the TRIDENT-1 study in the ROS1-positive TKI-naïve NSCLC patient cohort. Zai Lab partner Turning Point Therapeutics has announced that they anticipate an FDA meeting during the first quarter of 2022 to discuss topline blinded independent central review (BICR) results for that cohort.

Initiate TRIDENT-2, a Phase 1b/2 combination study in KRAS-mutant solid tumors.
Provide a clinical data update from the ongoing TRIDENT-1 study.

Report initial clinical data from the Phase 1/2 CARE study in pediatric and young adult patients.
MARGENZA (Margetuximab)

MARGENZA is an Fc-optimized monoclonal antibody that targets the human epidermal growth factor receptor 2 (HER2).

Anticipated 2021 Zai Milestone

Submit an NDA for pretreated metastatic HER2-positive breast cancer around year-end.
Anticipated 2021 Partner Milestones

Obtain initial data from Module A of the MAHOGANY study in the third quarter.

Complete the final overall survival analysis of the SOPHIA study, a randomized, open-label Phase 3 study evaluating margetuximab plus chemotherapy compared to trastuzumab plus chemotherapy in patients with HER2-positive metastatic breast cancer who have previously been treated with HER2-targeted therapies, in the third quarter.
Bemarituzumab

Bemarituzumab is a first-in-class antibody that is being developed in gastric and gastroesophageal junction cancer as a targeted therapy for tumors that overexpress FGFR2b.

Recent Product Highlight

In April 2021, Zai Lab partner Amgen was granted Breakthrough Therapy Designation by the FDA for bemarituzumab as first-line treatment for patients with FGFR2b overexpression in HER2-negative metastatic and locally advanced gastric and gastroesophageal adenocarcinoma in combination with modified FOLFOX6 (fluoropyrimidine, leucovorin, and oxaliplatin).
Anticipated 2021 Partner Milestone

Initiate a registrational Phase 3 study in gastric cancer in the fourth quarter.

Plan for clinical development in other FGFR2b+ solid tumors, including squamous cell NSCLC.
CLN-081

CLN-081 is an orally available, small-molecule, next-generation, irreversible epidermal growth factor receptor (EGFR) inhibitor designed to selectively target cells expressing mutant EGFR variants, including EGFR exon 20 insertions.

Recent Product Highlight

In June 2021, Zai Lab partner Cullinan announced Phase 1/2a interim data of CLN-081 in NSCLC EGFR exon 20 patients. CLN-081 continued to demonstrate acceptable overall safety and tolerability, with an encouraging GI toxicity profile.
Anticipated 2021 Partner Milestone

Initiate a potentially registrational Phase 2b clinical trial.
TPX-0022

TPX-0022 is an orally bioavailable, multi-targeted kinase inhibitor with a novel three-dimensional macrocyclic structure that inhibits the MET, CSF1R (colony stimulating factor 1 receptor) and SRC kinases.

Recent Product Highlight

In August and June 2021, Zai Lab partner Turning Point Therapeutics was granted Fast Track Designation and Orphan Drug Designation, respectively, by the FDA for TPX-0022 in gastric cancer.
Anticipated 2021 Partner Milestones

Provide a clinical data update from the dose-finding portion of the Phase 1 SHIELD-1 study and initiate the Phase 2 portion of the SHIELD-1 study, pending FDA feedback.

Initiate SHIELD-2, a Phase 1b/2 combination study with an epidermal growth factor receptor- (EGFR-) targeted therapy.
Tebotelimab

Tebotelimab is an investigational, first-in-class, bispecific, tetravalent DART molecule targeting PD-1 and LAG-3.

Recent Product Highlight

Zai Lab expanded the Phase 1b/2 study of tebotelimab in combination with ZEJULA into new indications in Greater China. In June and July 2021, Zai Lab enrolled the first patients in the biliary tract cancer and triple negative breast cancer cohorts, respectively.
Anticipated 2021 Zai and Partner Milestone

Provide a clinical update, including future development plans.
Autoimmune Diseases

Efgartigimod

Efgartigimod is an antibody fragment designed to reduce disease-causing immunoglobulin G (IgG) antibodies and block the IgG recycling process. Efgartigimod binds to the neonatal Fc receptor (FcRn), which is widely expressed throughout the body and plays a central role in rescuing IgG antibodies from degradation.

Recent Product Highlights

In July 2021, Zai Lab partner argenx announced plans to develop two new indications for efgartigimod: myositis and bullous pemphigoid.

In June 2021, Zai Lab partner argenx announced that The Lancet Neurology published pivotal trial results from the Phase 3 ADAPT trial of efgartigimod for the treatment of adults with generalized myasthenia gravis (gMG).

To date, five Clinical Trial Applications (CTAs) have been approved by the NMPA.
Anticipated 2021 Zai Milestones

Discuss with the NMPA a potential accelerated regulatory pathway for efgartigimod in gMG.

Continue to explore and advance additional indications in coordination with argenx.
Enroll the first patients in Greater China in the global pivotal Phase 3 trials of the subcutaneous formulation in primary immune thrombocytopenia (ITP) and pemphigus vulgaris (PV).

Expect CTA submissions for additional indications.
Anticipated 2021 Partner Milestones

Potential FDA approval, with a Prescription Drug User Fee Act (PDUFA) target action date of December 17, 2021, and global commercial launch of efgartigimod for the treatment of patients with gMG.

Initiate clinical trials in myositis and bullous pemphigoid.
Infectious Disease

NUZYRA (omadacycline)

NUZYRA is a once-daily oral and intravenous antibiotic for the treatment of adults with CABP and ABSSSI.

Recent Product Highlight

In June 2021, Zai Lab partner Paratek Pharmaceuticals announced the sNDA approval from the FDA of the NUZYRA oral-only dosing regimen for the treatment of CABP.
Anticipated 2021 Zai Milestone

Potential NMPA approval and commercial launch of NUZYRA for the treatment of CABP and ABSSSI.
Sulbactam-Durlobactam (SUL-DUR)

Sulbactam-Durlobactam is a beta-lactam/beta-lactamase inhibitor combination that provides unique activity against Acinetobacter organisms, including carbapenem-resistant strains.

Recent Product Highlight

In July 2021, Zai Lab and its partner Entasis Therapeutics completed patient enrollment in the global registrational Phase 3 ATTACK clinical trial.
Anticipated 2021 Zai and Partner Milestone

Announce the top-line data readout of the global registrational Phase 3 ATTACK clinical trial early in the fourth quarter.
Clinical Programs with Global Rights

ZL-1102 (IL-17 Nanobody)

ZL-1102 is a novel human nanobody targeting IL-17 with high affinity and avidity. Unlike other anti-IL-17 products, ZL-1102 is being developed as a topical treatment for chronic plaque psoriasis (CPP).

Anticipated 2021 Zai Milestone

Announce the top-line data readout of the global Phase 1 study.
ZL-1201 (CD47)

ZL-1201 is a humanized, IgG4 monoclonal antibody, engineered to reduce effector function, that specifically targets CD47. Its therapeutic potential will be assessed in both solid tumors and hematological malignancies and in both monotherapy and combination opportunities.

Anticipated 2021 Zai Milestone

Determine a recommended Phase 2 dose in the ongoing Phase 1 trial.
Simurosertib, ZL-2309 (CDC7)

Simurosertib, or ZL-2309, is a potential first-in-class oral selective inhibitor of CDC7, a protein kinase with key roles in DNA replication and in bypassing DNA damage response.

Anticipated 2021 Zai Milestone

Initiate a Phase 2 proof-of-concept study by year-end.
Business Development Updates

In July 2021, Zai Lab and Schrödinger, Inc., announced a global discovery, development and commercialization collaboration focused on a novel DNA damage repair target in oncology. Schrödinger is a recognized leader in providing physics-based computational software platforms used in drug discovery. The research program will be conducted jointly by the scientific teams of the two companies. Following the selection of a development candidate, Zai Lab will assume primary responsibility for global development, manufacturing and commercialization in the program. This initiative will complement Zai’s existing discovery efforts in the DNA damage response pathway in addition to potential combinations with existing Zai Lab products such as the PARP inhibitor ZEJULA and ZL-2309.

In June 2021, Zai Lab and Mirati announced that the companies entered into a collaboration and license agreement for adagrasib, a small-molecule KRASG12C inhibitor, in Greater China. Under the terms of the agreement, Zai Lab obtains the right to research, develop, manufacture and exclusively commercialize adagrasib in Greater China. Zai Lab will support accelerated enrollment in key global, registration-enabling clinical trials of adagrasib in patients with cancer who have a KRASG12C mutation.

In June 2021, Zai Lab and MacroGenics announced that the companies entered into an exclusive collaboration and license agreement involving up to four immuno-oncology molecules. The first collaboration program covers a lead research molecule that incorporates MacroGenics’ DART platform and binds CD3 and an undisclosed target that is expressed in multiple solid tumors. The second collaboration program covers a target to be designated by MacroGenics. For both molecules, Zai receives commercial rights in Greater China, Japan, and Korea, and MacroGenics receives commercial rights in all other territories. For the lead molecule, Zai Lab receives an option to convert the regional arrangement into a global 50/50 profit share upon reaching a predefined clinical milestone. Zai Lab also obtains exclusive, global licenses from MacroGenics to develop, manufacture and commercialize two additional molecules.
Corporate Updates

Zai Lab plans to host a virtual R&D Day on September 22, 2021, to provide a comprehensive update on our business and expanding pipeline across oncology, autoimmune and infectious diseases. Additional details will be announced at a later date.

Zai Lab continues to strengthen and expand its team. New hires include Danielle Halstrom, Senior Vice President, Global Head of Communications, and Jean Wang, PhD, Senior Vice President, Small Molecule CMC.

As of June 30, 2021, Zai Lab employed 1,600 full-time employees, including 594 and 832 employees engaged in research & development (R&D) and commercial activities, respectively.

We continue to invest in our global organization and facilities. During September, we plan to expand our presence in the United States by opening a clinical development and business facility in Cambridge, MA, to tap into the Boston area biopharmaceutical ecosystem. This facility complements our growing R&D and business center in the San Francisco Bay area.
Second-Quarter 2021 Financial Results

For the three months ended June 30, 2021, net product revenues were $36.9 million, compared to $11.0 million for the same period in 2020. Revenues for the period were comprised of $23.4 million for ZEJULA, compared to $7.5 million for the same period in 2020; $9.5 million for Optune, compared to $3.5 million for the same period in 2020; and $4.0 million for QINLOCK, compared to nil for the same period in 2020.

R&D expenses were $142.2 million for the three months ended June 30, 2021, compared to $68.3 million for the same period in 2020. The increase in R&D expenses was primarily attributable to a $65 million upfront payment to Mirati and a $25 million upfront payment to MacroGenics; expenses related to ongoing and newly initiated late-stage clinical trials; and payroll and payroll-related expenses from increased R&D headcount.

Selling, General and Administrative expenses (SG&A) were $54.4 million for three months ended June 30, 2021, compared to $23.8 million for the same period in 2020. The increase was primarily due to payroll and payroll-related expenses from increased commercial headcount and expanded commercial activities in China.

For the three months ended June 30, 2021, Zai Lab reported a net loss of $163.3 million, or a loss per share attributable to common stockholders of $1.76, compared to a net loss of $80.6 million, or a loss per share attributable to common stockholders of $1.08, for the same period in 2020. The increase in the net loss was primarily attributable to payments related to new business development activities with Mirati and MacroGenics recorded in R&D expenses.
As of June 30, 2021, cash and cash equivalents, short-term investments and restricted cash totaled $1,767.3 million compared to $1,187.5 million as of December 31, 2020.
Conference Call and Webcast Information

Zai Lab will host a live conference call and webcast today, August 10, 2021, at 8:00 a.m. EDT. Listeners can 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: View Source

Conference ID: 7290113
All participants must use the link provided above to complete the online registration process in advance of the conference call. Upon registering, each participant will receive a dial-in number, Direct Event passcode and a unique access PIN, which can be used to join the conference call.

A replay will be available shortly after the call and can be accessed by visiting the Company’s website at View Source