On December 12, 2023 Johnson & Johnson reported the first data from the Phase 3 PERSEUS study highlighting significant clinical improvement with a DARZALEX FASPRO (daratumumab and hyaluronidase-fihj)-based quadruplet induction, consolidation regimen and doublet maintenance regimen in the treatment of transplant-eligible (TE) newly diagnosed multiple myeloma (NDMM) (Press release, Johnson & Johnson, DEC 12, 2023, View Source [SID1234638512]). The data, showing an unrivaled progression-free survival (PFS) in a Phase 3 study evaluating TE NDMM and clinically significant improvement of rates of overall complete response (CR) or better and minimal residual disease (MRD) negativity over the comparator arm, were featured as a late-breaking oral presentation at the 2023 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (Abstract #LBA-1). The data were published simultaneously in The New England Journal of Medicine.

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The PERSEUS study, conducted in collaboration with the European Myeloma Network, found that induction and consolidation treatment with DARZALEX FASPRO in combination with bortezomib, lenalidomide and dexamethasone (D-VRd), followed by DARZALEX FASPRO and lenalidomide (D-R) maintenance, reduced the risk of disease progression or death by 58 percent (Hazard Ratio [HR], 0.42; 95 percent Confidence Interval [CI] 0.30-0.59; P <0.0001), compared to bortezomib, lenalidomide and dexamethasone (VRd) alone followed by lenalidomide (R) maintenance.1 The quadruplet regimen also significantly increased the depth of response compared to treatment with VRd alone, with higher rates of CR or better, stringent complete response (sCR), and MRD negativity.

"The progression-free survival that was achieved in transplant-eligible patients who were treated with the daratumumab-based induction, consolidation and maintenance therapy regimen is unprecedented in a Phase 3 clinical study evaluating this patient population, but is not unexpected as these findings build on a number of studies that previously demonstrated clinical benefit with daratumumab-based regimens in this patient population," said Pieter Sonneveld, M.D., Ph.D., Professor of Hematology at the Erasmus University of Rotterdam and Chair of the Erasmus MC Cancer Institute, Rotterdam, Netherlands.‡ "The results we see across clinically relevant subgroups, including in patients who present with advanced disease or who are considered high risk, are promising for clinicians who are on the frontlines of treating patients who are newly diagnosed with this complex disease."

The estimated 48-month PFS rates were 84.3 percent for D-VRd vs 67.7 percent for VRd. The consistent PFS improvement with D-VRd vs VRd was observed across most clinically relevant subgroups, including patients with International Staging System (ISS) stage III disease (HR, 0.42; 95 percent CI, 0.22-0.83) or high cytogenetic risk (HR, 0.59; 95 percent CI, 0.36-0.99). Treatment with D-VRd also resulted in deeper responses compared with VRd, including higher rates of sCR (69.3 percent vs 44.6 percent; P <0.0001), and ≥CR (87.9 percent vs 70.1 percent; P <0.0001). Overall MRD negativity rates (10–5) were higher with D-VRd vs VRd (75.2 percent vs 47.5 percent; P <0.0001). Sustained MRD-negativity rates (for ≥12 months) more than doubled with D-VRd (64.8 percent vs 29.7 percent; P <0.0001). Overall survival (OS) data are not yet mature but trending favorably for the D-VRd arm compared to VRd.

"We now have evidence supporting this DARZALEX-based quadruplet induction and consolidation regimen and doublet maintenance regimen as a potential new standard of care in transplant-eligible disease, complementing data from the Phase 3 MAIA study, which firmly established a DARZALEX-based triplet therapy as standard of care in transplant-ineligible disease," said Craig Tendler, M.D., Vice President, Late Development and Global Medical Affairs, Johnson & Johnson Innovative Medicine. "We will continue to advance innovative regimens and approaches with DARZALEX to deliver on our commitment of transforming outcomes for patients with multiple myeloma."

The overall safety profile of D-VRd was consistent with the known safety profiles for daratumumab and VRd. The most common (>10 percent) Grade 3/4 hematologic and non-hematologic adverse events (AE) with D-VRd vs VRd were neutropenia (62.1 percent vs 51.0 percent), thrombocytopenia (29.1 percent vs 17.3 percent), diarrhea (10.5 percent vs 7.8 percent), pneumonia (10.5 percent vs 6.1 percent) and febrile neutropenia (9.4 percent vs 10.1 percent).

About the PERSEUS study

The PERSEUS study is being conducted in collaboration with the European Myeloma Network as sponsor. PERSEUS is an ongoing, randomized, open-label, Phase 3 study comparing the efficacy and safety of D-VRd followed by D-R maintenance vs VRd followed by R maintenance in patients with transplant-eligible NDMM. The primary endpoint was PFS, and secondary endpoints included overall CR or better rate, overall MRD-negativity (in patients with CR or better), and overall survival. The median age is 61.0 (32-70) years for patients in the D-VRd arm and 59.0 (31-70) years for patients in the VRd arm. The study is being conducted in 14 countries in Europe and Australia.

About multiple myeloma

Multiple myeloma is an incurable blood cancer that affects a type of white blood cell called plasma cells, which are found in the bone marrow.2 In multiple myeloma, these plasma cells change, spread rapidly and replace normal cells in the bone marrow with tumors.3 Multiple myeloma is the third most common blood cancer and remains an incurable disease.4 In 2023, it is estimated that more than 35,000 people will be diagnosed with multiple myeloma in the U.S. and more than 12,000 people will die from the disease.5 People living with multiple myeloma have a 5-year survival rate of 59.8 percent.6 While some people diagnosed with multiple myeloma initially have no symptoms, most patients are diagnosed due to symptoms that can include bone fracture or pain, low red blood cell counts, tiredness, high calcium levels and kidney problems or infections.7,8

About DARZALEX FASPRO and DARZALEX

DARZALEX FASPRO (daratumumab and hyaluronidase-fihj) received U.S. FDA approval in May 2020 and is approved for eight indications in multiple myeloma, three of which are for frontline treatment in newly diagnosed patients who are transplant eligible or ineligible.9 It is the only subcutaneous CD38-directed antibody approved to treat patients with MM. DARZALEX FASPRO is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), Halozyme’s ENHANZE drug delivery technology.

DARZALEX (daratumumab) received U.S. FDA approval in November 2015 and is approved in eight indications, three of which are in the frontline setting, including newly diagnosed patients who are transplant eligible and ineligible.10

DARZALEX is the first CD38-directed antibody approved to treat multiple myeloma.11 DARZALEX-based regimens have been used in the treatment of more than 422,000 patients worldwide and more than 68,000 patients in the U.S. alone.

In August 2012, Janssen Biotech, Inc. and Genmab A/S entered a worldwide agreement, which granted Janssen an exclusive license to develop, manufacture and commercialize daratumumab. 

Since 2020, the National Comprehensive Cancer Network (NCCN) has recommended daratumumab-based combination regimens for the treatment of newly diagnosed multiple myeloma and relapsed and refractory multiple myeloma.† For newly diagnosed multiple myeloma in non-transplant candidates, the NCCN guidelines recommend daratumumab in combination with lenalidomide and dexamethasone as a Category 1 preferred regimen; daratumumab in combination with bortezomib, melphalan, and prednisone as another recommended Category 1 regimen; and daratumumab in combination with bortezomib, cyclophosphamide, and prednisone as another recommended Category 2A regimen. For newly diagnosed multiple myeloma in transplant candidates, the NCCN guidelines recommend daratumumab in combination with bortezomib, lenalidomide and dexamethasone as another recommended Category 2A regimen; daratumumab in combination with bortezomib, thalidomide and dexamethasone as a Category 2A regimen useful in certain circumstances; daratumumab in combination with carfilzomib, lenalidomide and dexamethasone as a Category 2A regimen useful in certain circumstances; and daratumumab in combination with cyclophosphamide, bortezomib and dexamethasone as a Category 2A regimen useful in certain circumstances. For maintenance in transplant candidates, the NCCN guidelines recommend daratumumab in combination with lenalidomide as useful in certain circumstances. In relapsed/refractory myeloma, four daratumumab regimens are listed as Category 1 preferred regimens for early relapses (1-3 prior therapies): daratumumab in combination with lenalidomide and dexamethasone; daratumumab in combination with bortezomib and dexamethasone; daratumumab in combination with carfilzomib and dexamethasone; and daratumumab in combination with pomalidomide and dexamethasone [after one prior therapy including lenalidomide and a proteasome inhibitor (PI)]. The NCCN also recommends daratumumab in combination with cyclophosphamide, bortezomib and dexamethasone as another Category 2A regimen for early relapses (1-3 prior therapies) and as monotherapy as a Category 2A regimen useful in certain circumstances for early relapse patients after at least three prior therapies, including a PI and an immunomodulatory agent, or for patients who are double refractory to a PI and an immunomodulatory agent.

For more information, visit www.DARZALEX.com.

DARZALEX FASPRO IMPORTANT SAFETY INFORMATION

INDICATIONS

DARZALEX FASPRO (daratumumab and hyaluronidase-fihj) is indicated for the treatment of adult patients with multiple myeloma:

In combination with bortezomib, melphalan, and prednisone in newly diagnosed patients who are ineligible for autologous stem cell transplant
In combination with lenalidomide and dexamethasone in newly diagnosed patients who are ineligible for autologous stem cell transplant and in patients with relapsed or refractory multiple myeloma who have received at least one prior therapy
In combination with bortezomib, thalidomide, and dexamethasone in newly diagnosed patients who are eligible for autologous stem cell transplant
In combination with pomalidomide and dexamethasone in patients who have received at least one prior line of therapy including lenalidomide and a proteasome inhibitor
In combination with carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy
In combination with bortezomib and dexamethasone in patients who have received at least one prior therapy
As monotherapy in patients who have received at least three prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent or who are double-refractory to a PI and an immunomodulatory agent
CONTRAINDICATIONS

DARZALEX FASPRO is contraindicated in patients with a history of severe hypersensitivity to daratumumab, hyaluronidase, or any of the components of the formulation.

WARNINGS AND PRECAUTIONS

Hypersensitivity and Other Administration Reactions

Both systemic administration-related reactions, including severe or life-threatening reactions, and local injection-site reactions can occur with DARZALEX FASPRO. Fatal reactions have been reported with daratumumab-containing products, including DARZALEX FASPRO.

Systemic Reactions

In a pooled safety population of 898 patients with multiple myeloma (N=705) or light chain (AL) amyloidosis (N=193) who received DARZALEX FASPRO as monotherapy or in combination, 9% of patients experienced a systemic administration-related reaction (Grade 2: 3.2%, Grade 3: 1%). Systemic administration-related reactions occurred in 8% of patients with the first injection, 0.3% with the second injection, and cumulatively 1% with subsequent injections. The median time to onset was 3.2 hours (range: 4 minutes to 3.5 days). Of the 140 systemic administration-related reactions that occurred in 77 patients, 121 (86%) occurred on the day of DARZALEX FASPRO administration. Delayed systemic administration-related reactions have occurred in 1% of the patients.

Severe reactions included hypoxia, dyspnea, hypertension, tachycardia, and ocular adverse reactions, including choroidal effusion, acute myopia, and acute angle closure glaucoma. Other signs and symptoms of systemic administration-related reactions may include respiratory symptoms, such as bronchospasm, nasal congestion, cough, throat irritation, allergic rhinitis, and wheezing, as well as anaphylactic reaction, pyrexia, chest pain, pruritus, chills, vomiting, nausea, hypotension, and blurred vision.

Pre-medicate patients with histamine-1 receptor antagonist, acetaminophen, and corticosteroids. Monitor patients for systemic administration-related reactions, especially following the first and second injections. For anaphylactic reaction or life-threatening (Grade 4) administration-related reactions, immediately and permanently discontinue DARZALEX FASPRO. Consider administering corticosteroids and other medications after the administration of DARZALEX FASPRO depending on dosing regimen and medical history to minimize the risk of delayed (defined as occurring the day after administration) systemic administration-related reactions.

Ocular adverse reactions, including acute myopia and narrowing of the anterior chamber angle due to ciliochoroidal effusions with potential for increased intraocular pressure or glaucoma, have occurred with daratumumab-containing products. If ocular symptoms occur, interrupt DARZALEX FASPRO and seek immediate ophthalmologic evaluation prior to restarting DARZALEX FASPRO.

Local Reactions

In this pooled safety population, injection-site reactions occurred in 8% of patients, including Grade 2 reactions in 0.7%. The most frequent (>1%) injection-site reaction was injection-site erythema. These local reactions occurred a median of 5 minutes (range: 0 minutes to 6.5 days) after starting administration of DARZALEX FASPRO. Monitor for local reactions and consider symptomatic management.

Neutropenia

Daratumumab may increase neutropenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer’s prescribing information for background therapies. Monitor patients with neutropenia for signs of infection. Consider withholding DARZALEX FASPRO until recovery of neutrophils. In lower body weight patients receiving DARZALEX FASPRO, higher rates of Grade 3-4 neutropenia were observed.

Thrombocytopenia

Daratumumab may increase thrombocytopenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer’s prescribing information for background therapies. Consider withholding DARZALEX FASPRO until recovery of platelets.

Embryo-Fetal Toxicity

Based on the mechanism of action, DARZALEX FASPRO can cause fetal harm when administered to a pregnant woman. DARZALEX FASPRO may cause depletion of fetal immune cells and decreased bone density. Advise pregnant women of the potential risk to a fetus. Advise females with reproductive potential to use effective contraception during treatment with DARZALEX FASPRO and for 3 months after the last dose.

The combination of DARZALEX FASPRO with lenalidomide, thalidomide, or pomalidomide is contraindicated in pregnant women because lenalidomide, thalidomide, and pomalidomide may cause birth defects and death of the unborn child. Refer to the lenalidomide, thalidomide, or pomalidomide prescribing information on use during pregnancy.

Interference with Serological Testing

Daratumumab binds to CD38 on red blood cells (RBCs) and results in a positive indirect antiglobulin test (indirect Coombs test). Daratumumab-mediated positive indirect antiglobulin test may persist for up to 6 months after the last daratumumab administration. Daratumumab bound to RBCs masks detection of antibodies to minor antigens in the patient’s serum. The determination of a patient’s ABO and Rh blood type are not impacted.

Notify blood transfusion centers of this interference with serological testing and inform blood banks that a patient has received DARZALEX FASPRO. Type and screen patients prior to starting DARZALEX FASPRO.

Interference With Determination of Complete Response

Daratumumab is a human immunoglobulin G (IgG) kappa monoclonal antibody that can be detected on both the serum protein electrophoresis (SPE) and immunofixation (IFE) assays used for the clinical monitoring of endogenous M-protein. This interference can impact the determination of complete response and of disease progression in some DARZALEX FASPRO-treated patients with IgG kappa myeloma protein.

ADVERSE REACTIONS

In multiple myeloma, the most common adverse reaction (≥20%) with DARZALEX FASPRO monotherapy is upper respiratory tract infection. The most common adverse reactions with combination therapy (≥20% for any combination) include fatigue, nausea, diarrhea, dyspnea, insomnia, headache, pyrexia, cough, muscle spasms, back pain, vomiting, hypertension, upper respiratory tract infection, peripheral sensory neuropathy, constipation, pneumonia, and peripheral edema.

The most common hematology laboratory abnormalities (≥40%) with DARZALEX FASPRO are decreased leukocytes, decreased lymphocytes, decreased neutrophils, decreased platelets, and decreased hemoglobin.

Please click here to see the full Prescribing Information.

On December 12, 2023 Dizal reported compelling data from its robust portfolio of hematological oncology at the 65th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition held in San Diego, California from December 9-12 (Press release, Dizal Pharma, DEC 12, 2023, View Source [SID1234638511]). The data showcased updated results of Dizal’s two leading assets: golidocitinib, the first and only JAK1 selective inhibitor for the treatment of peripheral T-cell lymphoma (PTCL), and DZD8586, a first-in-class LYN and BTK dual inhibitor for the treatment of relapsed or refractory (r/r) B-cell non-Hodgkin lymphoma (B-NHL). This underscores Dizal’s dedication to developing and delivering innovative, life-changing medicines in the field of hematological oncology.

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Golidocitinib

The first and only JAK1 selective inhibitor for the treatment of PTCL

Golidocitinib, a novel JAK1-only inhibitor developed by Dizal, is currently in the NDA stage for the treatment of r/r PTCL. The China National Medical Products Administration (NMPA) recognized its potential and granted it Priority Review in September 2023. Notably, golidocitinib stands as the world’s first and only highly selective JAK1 inhibitor specifically developed for PTCL. Furthermore, it has obtained Fast Track Designation from the U.S. Food and Drug Administration (FDA), positioning it as the first Chinese innovative PTCL drug to receive this designation.

The efficacy of golidocitinib in PTCL was highlighted at 2023 ASH (Free ASH Whitepaper), with two studies being selected for presentation. Particularly noteworthy is the multinational, pivotal study of golidocitinib for the treatment of r/r PTCL (JACKPOT8 PART B), which was selected for oral presentation and simultaneously published in the peer-reviewed journal The Lancet Oncology (Impact Factor: 54.4).

The potential best-in-class treatment option for r/r PTCL

There is no consensus on the standard treatment for r/r PTCL and the 5-year survival rate is below 30%. The results of JACKPOT8 PART B study revealed that golidocitinib demonstrated superior and durable clinical benefits in the treatment of r/r PTCL with a favorable safety profile that outperformed existing treatment options. Per independent review committee (IRC) assessment, golidocitinib achieved an overall response rate (ORR) of 44.3% and a complete response rate (CRR) of 23.9%. Both were more than double that of existing treatment options. Tumor responses were observed across various PTCL subtypes. The responses were durable, with the median duration of response (mDoR) of 20.7 months. This is higher than the DoR observed with existing therapies, which is typically below 12 months. The median progression-free survival (mPFS) was 5.6 months, and the median overall survival (mOS) was 19.4 months and still ongoing.

Promising and durable efficacy in PTCL after first-line systemic therapy

Approximately 40% of patients with complete response (CR) and 80% of patients with partial response (PR) have disease relapse within 2 years after initial tumor response. These patients currently lack a standard maintenance therapy.

JACKPOT 26 is a phase 2, single-arm, multicenter study to evaluate the safety and efficacy of golidocitinib for maintenance treatment after first-line therapy. At the data cut-off date of October 12, 2023, in the cohort of patients achieving CR post first-line therapy, median disease-free survival (DFS) has not been reached, with 76.7% patients still event free. In the cohort of patients achieving PR post first-line therapy, median DoR has not been reached, with 33% of patients achieving a CR and 85.7% of patients still responding to the treatment. The median PFS was 16.7 months. The treatment-related adverse events (TRAEs) observed in this study were similar to those previously reported for golidocitinib and were clinically manageable and reversible.

DZD8586

A first-in-class non-covalent LYN and BTK dual inhibitor with excellent blood-brain barrier (BBB) penetration

DZD8586 is a rationally designed, oral, non-covalent, LYN/BTK dual inhibitor with excellent BBB penetration as a potential treatment option for B-NHL. While Bruton’s Tyrosine Kinase (BTK) inhibitors have been approved for the treatment of B-NHL, resistance can emerge due to various mechanisms. This includes acquired mutations at residue C481X of BTK which disrupts covalent BTKi binding, as well as non BTK-driven mutations that seems more common in patients who have failed non-covalent BTKi such as pirtobrutinib. Currently, there is no targeted therapy available to address both resistance mechanisms, highlighting an urgent need for a safe and effective treatment option for patients with r/r B-NHL.

Potential to overcome resistance to both covalent and non-covalent BTK inhibitors

Preclinical studies have shown that DZD8586 can overcome resistance mutations observed with approved covalent and non-covalent BTK inhibitors. DZD8586 has exhibited potent inhibition of cell growth by blocking both BTK-dependent and BTK-independent signaling pathways.

No BTK inhibitor has been approved for treating diffuse large B-cell lymphoma (DLBCL). It is hypothesized that blockage of BTK pathway alone is not sufficient to bring meaningful clinical benefit in DLBCL. DZD8586 shows strong inhibition of LYN and BTK phosphorylation and achieves superior anti-tumor efficacy in DLBCL and chronic lymphocytic leukemia (CLL) models than selective BTK inhibitors. Due to limited BBB penetration of the current therapies, treatment of central nervous system lymphoma (CNSL) remains a clinical challenge. DZD8586 indicated CNS penetration with the potential to treat CNSL.

A novel treatment option for r/r B-NHL

DZD8586 is currently being evaluated in two phase 1/2 clinical trials for patients with r/r B-NHL worldwide. At 2023 ASH (Free ASH Whitepaper), the pooled analysis from the two studies were debuted. The results revealed that DZD8586 showed encouraging anti-tumor activity with manageable safety and favorable PK profile in heavily pre-treated B-NHL patients. Highlights of the study findings include:

ORR of 64.7% across all dose levels, 71.4% at 50 mg
Tumor response in different subtypes, including DLBCL (ORR 83.3%), CNSL, and CLL
ORR of 50% in patients resistant to BTKi treatment
"Our research findings presented at ASH (Free ASH Whitepaper) demonstrate Dizal’s distinctive competitiveness in the field of hematological oncology. We are fully committed to pushing the boundaries of innovation and developing transformative drugs to improve the lives of patients globally." said Xiaolin Zhang, PhD, Chairman and CEO of Dizal.

On December 12, 2023 Shanghai Henlius Biotech, Inc. (2696.HK) reported that the NDA for new indication of HANSIZHUANG, serplulimab, an innovative anti-PD-1 mAb independently developed by the company, in combination with chemotherapy as a first-line treatment for patients with locally advanced or metastatic non-squamous non-small cell lung cancer (nsNSCLC) has been accepted by the National Medical Products Administration (NMPA), which is the fifth indication for HANSIZHUANG accepted by the NMPA (Press release, Shanghai Henlius Biotech, DEC 12, 2023, View Source [SID1234638510]). To date, HANSIZHUANG has been approved for the treatment of microsatellite instability-high (MSI-H) solid tumors, squamous non-small cell lung cancer (sqNSCLC), extensive-stage small cell lung cancer (ES-SCLC) and esophageal squamous cell carcinoma (ESCC).

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Lung cancer is the cancer with the highest global mortality rate. According to the latest data released by the International Agency for Research on Cancer (IARC) of the World Health Organization, the number of cancer deaths worldwide in 2020 reached 9.96 million, of which approximately 1.8 million died from lung cancer, accounting for 18%. In China, the incidence rate and mortality of lung cancer rank first, and the incidence rate is increasing year by year. The non-small cell lung cancer (NSCLC) is the most common histological type of lung cancer, accounting for about 85% of lung cancer patients, among which nsNSCLC has the highest incidence rate. In the treatment of NSCLC, immune checkpoint inhibitors (ICI), such as PD-1/PD-L1, have developed rapidly, notably, the anti-PD-1 mAb plus chemotherapy has been recommended by the latest NCCN guidelines and CSCO guidelines as the first-line treatment for nsNSCLC, and serplulimab therefore is expected to bring a new option for patients.

The NDA for new indication of HANSIZHUANG is mainly based on a randomized, double-blind, multi-center phase 3 clinical study of HANSIZHUANG in combination with chemotherapy, or chemotherapy as a first-line treatment for patients with advanced non-squamous non-small cell lung cancer. The study results demonstrated that HANSIZHUANG in combination with chemotherapy significantly prolonged progression-free survival (PFS) compared with chemotherapy, which has met the pre-specified superiority criteria, with good safety and no detection of new safety signal.

HANSIZHUANG, Henlius’ first self-developed innovative monoclonal antibody, focuses on lung and gastrointestinal cancer and has initiated more than 10 clinical studies on immuno-oncology combination therapies worldwide. It covers the full range of first-line treatment of lung cancer, in which a head-to-head bridging trial of HANSIZHUANG versus first-line standard-of-care atezolizumab for ES-SCLC was launched in the U.S. in 2022, which is beneficial for its registration and commercialization in the U.S. In addition, the Marketing Authorization Application (MAA) for HANSIZHUANG on ES-SCLC has been validated by the European Medicines Agency (EMA), with approval expected in the first half of 2024. Previously, HANSIZHUANG was also granted orphan drug designations by the U.S. Food and Drug Administration (FDA) and European Commission (EC) for the treatment of SCLC. Furthermore, Henlius is steadily advancing a global phase 3 multi-center clinical research of HANSIZHUANG for the limited stage small cell lung cancer (LS-SCLC) and its first patients in China, the U.S., Europe, and Australia have been dosed, respectively.

In the future, Henlius will continue to improve its innovation capabilities to meet patients’ needs and create greater clinical value, aiming to provide more accessible, affordable, and high-quality products and solutions to patients around the world.

About HANSIZHUANG

HANSIZHUANG (recombinant humanized anti-PD-1 monoclonal antibody injection, generic name: serplulimab injection) is the first anti-PD-1 mAb for the first-line treatment of SCLC. Up to date, 4 indications are approved for marketing in China, 2 marketing applications are under review in China and the EU, and more than 10 clinical trials are ongoing across the world.

HANSIZHUANG was launched in March 2022 and has been approved by the NMPA for the treatment of MSI-H solid tumours, squamous non-small cell lung cancer (sqNSCLC), extensive-stage small cell lung cancer (ES-SCLC), and esophageal squamous cell carcinoma (ESCC). Its marketing application of the first-line treatment for ES-SCLC is under review by the EMA. Focusing on lung and gastrointestinal cancer, the synergy of HANSIZHUANG with in-house products of the company and innovative therapies are being actively promoted. It has successively obtained clinical trial approvals in China, the U.S., the EU and other countries and regions to initiate more than 10 clinical trials on immuno-oncology combination therapies in a wide variety of indications. As of now, the company has enrolled more than 3,600 subjects in China, the U.S., Turkey, Poland, Georgia and other countries and regions, and the proportion of White is over 30% in two MRCTs, making HANSIZHUANG an anti-PD-1 mAb with one of the largest global clinical data pools. The results of 3 pivotal trials of HANSIZHUANG were published in the Journal of the American Medical Association (JAMA), Nature Medicine and the British Journal of Cancer, respectively. Furthermore, HANSIZHUANG was recommended by the CSCO Guidelines for Small Cell Lung Cancer, the CSCO Guidelines for Non-Small Cell Lung Cancer, the CSCO Guidelines for Esophageal Cancer, the CSCO Guidelines for Colorectal Cancer, the CSCO Clinical Practice Guidelines on Immune Checkpoint Inhibitor, the China Guidelines for Radiotherapy of Esophageal Cancer, and other definitive guides, providing valuable references for clinical diagnosis and treatment of tumours. On the other hand, serplulimab was granted orphan drug designations by the U.S. FDA and the EC for the treatment of SCLC, and its bridging head-to-head trial in the United States to compare HANSIZHUANG to standard of care atezolizumab (anti-PD-L1 mAb) for the first-line treatment of ES-SCLC is well under way.

On December 12, 2023 ESSA Pharma Inc. ("ESSA", or the "Company") (NASDAQ: EPIX), a clinical-stage pharmaceutical company, focused on developing novel therapies for the treatment of prostate cancer, reported a corporate update and announced financial results for the fourth quarter and fiscal year ended September 30, 2023 (Press release, ESSA, DEC 12, 2023, View Source [SID1234638508]).

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"We are pleased with the progress made in 2023 with masofaniten (EPI-7386), our first-in-class N-terminal domain androgen receptor inhibitor for the treatment of prostate cancer, which culminated recently in the presentation of Phase 1 dose escalation data at two medical meetings where we showed that the combination of masofaniten with enzalutamide was well-tolerated and demonstrated deep and durable reductions in prostate-specific antigen ("PSA") in patients with metastatic castration-resistant prostate cancer ("mCRPC")," said David Parkinson, MD, President and CEO of ESSA. "Looking ahead, we will be focused on executing the Phase 2 combination study of masofaniten and enzalutamide in mCRPC patients as well as investigating masofaniten in combination with other standard of care antiandrogens to further elucidate its potential as a new treatment for prostate cancer patients at earlier stages of the disease. We are entering 2024 with a strong cash balance and a runway that is expected to fund our planned operations through 2025."

Fourth Quarter Fiscal 2023 and Recent Highlights

Masofaniten Combination Studies

Reported updated Phase 1 dose escalation data from the four cohorts of its ongoing Phase 1/2 study evaluating masofaniten in combination with enzalutamide in patients with mCRPC naïve to second-generation antiandrogens but may have been treated with chemotherapy in the metastatic castration-sensitive setting. The results demonstrated that the combination continues to be well-tolerated with deep and durable reductions in PSA. Across all dose cohorts (n=16) including patients in the recently enrolled Cohort 4, 88% of patients achieved PSA50, 81% of patients achieved PSA90, 69% of patients achieved PSA90 in less than 90 days, and 56% of patients achieved PSA <0.2ng/mL. These data were presented at the 2023 Prostate Cancer Foundation Scientific Retreat and at the European Society for Medical Oncology 2023 Congress.
Initiated the Phase 2 portion of its Phase 1/2 study evaluating the combination of masofaniten and enzalutamide compared to enzalutamide monotherapy in patients with mCRPC naïve to second-generation antiandrogens but may have been treated with chemotherapy in the metastatic castration-sensitive setting. The Phase 2 portion of the study is an open-label randomized study comparing 160 mg once-daily of single agent enzalutamide to the combination of masofaniten with enzalutamide, and is expected to enroll approximately 120 patients. The recommended Phase 2 combination dose was identified as masofaniten 600 mg twice-daily combined with enzalutamide 160 mg once daily. ESSA plans to provide guidance for timing of the public disclosure of initial data once the Phase 2 portion has been underway for several months.
Initiated two additional masofaniten combination arms as part of the ongoing Phase 1 masofaniten study. One arm will evaluate masofaniten in combination with abiraterone acetate and prednisone in patients with either metastatic castration-sensitive prostate cancer ("mCSPC") or mCRPC while the second arm will evaluate masofaniten in combination with apalutamide in patients with non-metastatic CRPC after 12 weeks of masofaniten single agent.
An investigator-sponsored neoadjuvant study was also initiated evaluating neoadjuvant use of the combination of masofaniten and darolutamide compared to darolutamide monotherapy in high-risk patients undergoing prostatectomy.
Masofaniten Monotherapy Study

On track to complete the Phase 1b masofaniten monotherapy study evaluating masofaniten in patients with late-line mCRPC. The initial results from the study were reported at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Genitourinary Cancers Symposium and demonstrated that masofaniten monotherapy was well-tolerated, achieved clinically significant exposures, and showed preliminary signals of anti-tumor activity in a subset of patients. ESSA plans to present the complete Phase 1a and 1b monotherapy results in 2024 at a medical conference.
Summary Financial Results
(Amounts expressed in U.S. dollars)

Net Loss. ESSA recorded a net loss of $26.6 million for the year ended September 30, 2023 compared to a net loss of $35.1 million for the year ended September 30, 2022. For the year ended September 30, 2023, this included non-cash share-based payments of $5.0 million compared to $7.9 million for the prior year, recognized for stock options granted and vesting. Net loss for the fourth quarter ended September 30, 2023 was $5.5 million compared to a net loss of $6.3 million for the fourth quarter ended September 30, 2022. The decrease in the fourth quarter was primarily attributed to a decrease in general and administration expenditures and an increase in interest and other income.
Research and Development ("R&D") expenditures. R&D expenditures for the year ended September 30, 2023 were $21.3 million compared to $24.4 million for the year ended September 30, 2022, and include non-cash costs related to share-based payments ($2.6 million for the year ended 2023 compared to $4.3 million for the year ended 2022). The decrease in R&D expenditures for the year ended September 30, 2023 was primarily attributed to decreases in preclinical and data analysis, share-based payments and manufacturing costs. R&D expenditures for the fourth quarter ended September 30, 2023 were $5.2 million compared to $4.4 million for the fourth quarter ended September 30, 2022. The primary drivers for the increase were due to increased clinical costs as the Company advances masofaniten through its clinical trials.
General and administration ("G&A") expenditures. G&A expenditures for the year ended September 30, 2023 were $10.8 million compared to $12.5 million for the year ended September 30, 2022, and include non-cash costs related to share-based payments of $2.4 million for the year ended 2023 compared to $3.6 million for the year ended 2022. G&A expenditures for the fourth quarter ended September 30, 2023 were $1.9 million compared to $2.8 million for the fourth quarter ended September 30, 2022. The decrease for the fourth quarter was primarily due to decreased share-based payments and lower insurance renewal premiums.
Liquidity and Outstanding Share Capital

At September 30, 2023, the Company had available cash reserves and short-term investments of $148.1 million. The Company’s cash position is expected to be sufficient to fund current and planned operations through 2025.
On November 6, 2023, the Company announced that it had entered into an Open Market Sale AgreementSM (the "ATM Sales Agreement") with Jefferies LLC, effective as of November 3, 2023. Under the ATM Sales Agreement, ESSA may, within the period that the ATM Sales Agreement is in effect, sell its common shares from time to time for up to $50.0 million in aggregate sales proceeds. No offers or sales of common shares will be made in Canada, to anyone known by Jefferies LLC to be a resident of Canada or on or through the facilities of any stock exchange or trading markets in Canada.
As of September 30, 2023, the Company had 44,100,838 common shares issued and outstanding.
In addition, as of September 30, 2023, there were 2,927,477 common shares issuable upon the exercise of warrants and broker warrants. This includes 2,920,000 prefunded warrants at an exercise price of $0.0001, and 7,477 warrants at a weighted average exercise price of $42.80. There were 8,112,774 common shares issuable upon the exercise of outstanding stock options at a weighted-average exercise price of $4.97 per common share.

On December 12, 2023 Shinobi Therapeutics (Shinobi), the biotechnology company developing a new class of immune evasive iPS-T cell therapies, reported that it has closed a $51 million Series A financing (Press release, Shinobi Therapeutics, DEC 12, 2023, View Source [SID1234638509]). The oversubscribed round was led by EQT Life Sciences, F-Prime Capital and Eight Roads Ventures Japan, with participation from Astellas Venture Management, Fast Track Initiative (FTI), JIC Venture Growth Investments, and D3 LLC. Shinobi will use the funds to advance its ‘Katana’ iPS-T cell therapy platform and progress its first program to treat GPC3+ solid tumor cancers toward the clinic.

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"We’re thrilled to launch Shinobi out of stealth with a clear mission to develop an all-in-one solution to address some of the biggest challenges facing the cell therapy space today," said Dan Kemp, Ph.D., Chief Executive Officer of Shinobi. "Having led several cell therapy programs at other global companies, I’ve never encountered a technology platform that is capable of advancing the field as dramatically as this."

Cell therapies have shown remarkable promise in treating blood cancers and other intractable diseases, but manufacturing costs render these therapies inaccessible to many patients around the world. Off-the-shelf cell therapies offer a more scalable manufacturing approach, but face the additional challenge of allo-rejection, as patients’ immune systems reject donor-derived and engineered cells as foreign invaders. To overcome this immune response, patients today receive immunosuppressive drugs before treatment, which can often result in unwanted side effects and serious complications. Shinobi is taking a different approach by creating therapies that work with, not against, the patient’s immune system.

Shinobi’s unique approach uses methods developed by scientific co-founders Tobias Deuse, M.D. and Shin Kaneko, M.D., Ph.D., to first edit iPSCs to become highly immune evasive before they are differentiated with the company’s proprietary Katana technology to create CD8αβ iPS-T cells. "Shinobi’s Katana platform has the potential to make CAR-T cell therapies accessible to patients on a global scale," said Carl June, M.D., who has been appointed to Shinobi’s Scientific Advisory Board.

"Shinobi stands alone in the growing cell therapy field by engineering the most comprehensive immune evasion technology directly into its cell products," said Robert Weisskoff, Ph.D, Partner at F-Prime Capital. "With our colleagues at Eight Roads Ventures Japan and Donald Payan M.D., we envisioned combining the decade’s worth of iPSC research pioneered by Shin Kaneko M.D., Ph.D and developed by Yasumichi Hitoshi M.D., Ph.D. and Ryosuke Gonotsubo in Kyoto, Japan, with breakthrough immune evasion technology created by Tobias Deuse, M.D. in San Francisco. Shinobi Therapeutics is the result of these merged technologies, which delivers an allogeneic platform that effectively protects cell therapies from T cells, innate immune cells, as well as antibody-mediated immune rejection."

"The full potential of allogeneic cell therapies will likely never be realized without overcoming the challenge of allo-rejection," said Fouad Azzam, Ph.D., Partner at EQT Life Sciences. "Shinobi’s hypoimmune technology opens the door to a broader pipeline of off-the-shelf cell therapies far beyond T cells and oncology. We’re planning to leverage this platform in important areas of regenerative medicine and autoimmune disease."