On July 18, 2023 ENB Therapeutics, Inc., a biotechnology company pioneering a new and differentiated class of therapeutics targeting the endothelin B receptor (ETBR) inhibitor, reported that the company has completed enrollment of its international Phase 1 ENBOLDEN-101 trial investigating the safety and efficacy of lead product ENB-003 in combination with KEYTRUDA (pembrolizumab), Merck’s anti-PD-1 therapy (Press release, ENB Therapeutics, JUL 21, 2023, View Source [SID1234634070]). The Phase ½a study is a multicenter, open-label study conducted in the US and Australia and is comprised of two parts. Part 1 recruited 46 patients and was a dose-escalation study to determine the recommended dose for the Part 2 expansion phase of the study. The results of this study will be presented by ENB Therapeutics in a poster titled, "ENB-003, an ETBR antagonist, in combination with pembrolizumab for refractory advanced solid tumors: Topline data from the ENBolden-101 Phase 1B study" at the Immuno-oncology Summit which is being held August 7-9, 2023 in Boston, Massachusetts.

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ENB-003 in combination with pembrolizumab was well tolerated in the dose escalation study and demonstrated no DLTs across the 6 dosing cohorts. The most common treatment emergent adverse events irrespective of grade or causality included fatigue (28.2%), constipation (26.1%), abdominal pain (26.1%), nausea (23.9%), anemia 17.4%, diarrhea (17.4%). Serious adverse events, grade 3 and above considered possibly related to study treatment included fatigue (n=4), diarrhea (n=3), dyspnea (n=3) constipation (n=2), rash (n=2). 15 patients with evaluable disease were enrolled in cohorts 1-5 (ENB-003 dose range 150ug-1000ug) and 15 patients with evaluable disease were enrolled in the 6th cohort (ENB-003 dose 2000ug). The dosing frequency for cohort 6 was doubled to 6 doses every 3 weeks from 6 doses every 6 weeks in cohort 1-5. The DCR across all cohorts irrespective of ETBR status was 33% (1 PR, 9 SD, 20 PD). The DCR in ETBR-Hi patients was 33% in cohorts 1-5 (4 SD, 1 PR, 10 PD) and 83% in cohort 6 (5 SD, 1 PD). The DCR for ETBR-Lo patients in cohort 6 was 0% (9 PD). ETBR-Lo patients were not enrolled in cohorts 1-5. For microsatellite stable (MSS) platinum refractory/ resistant ovarian cancer there was an 80% DCR across all cohorts (1 PR, 3 SD, 1 PD) with a trend for durable responses at higher doses of ENB-003. A platinum refractory MSS ovarian cancer patient experienced a 95% PR of 12-month duration. The sample size was not powered for statistical significance.

"The completion of enrollment of the Phase 1 ENBOLDEN-101 first-in-man study is a significant milestone for our Company. We are extremely encouraged by the results in heavily treated cancer patients refractory to standard of care treatment," stated Sumayah Jamal, MD-PhD, President, Chief Scientific Officer and Co-Founder of ENB Therapeutics. "Our data suggest potential efficacy in patients that do not historically respond to immunotherapy and support further clinical development. We are grateful to our patients and their families for their participation in our study. "

Part 2 is a dose expansion study at the recommended dose designed to evaluate the safety, tolerability and efficacy of ENB-003 in combination with pembrolizumab in cancers refractory to standard of care including MSS R/R ovarian cancer, MSS pancreatic cancer, anti-PD1 refractory HNSCC, anti-PD1 refractory melanoma and anti-PD1 refractory TNBC. For more information on this Phase 1/2a study, see NCT04205227.

KEYTRUDA is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

About ENB-003

ENB-003 is a selective endothelin B receptor (ETBR) inhibitor that, in preclinical studies, enhances efficacy of CAR-T and anti-PD-1 in solid tumors across multiple cancer types in preclinical studies. In an ongoing multi-center Phase 1/2 clinical trial, early efficacy signals suggest that ENB-003 overcomes resistance to the anti-PD-1 therapy KEYTRUDA (pembrolizumab) in heavily pre-treated drug resistant cancer patients. The Phase 2 portion of the ENB-003 + pembrolizumab combination study is expected to start in the first half of 2024. The trial will enroll microsatellite stable platinum refractory and primary platinum resistant ovarian cancer patients, as well as microsatellite stable pancreatic cancer patients that have failed standard of care.

On July 21, 2023 BeiGene (Nasdaq: BGNE; HKEX: 06160; SSE: 688235), a global biotechnology company, reported that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion recommending approval for tislelizumab as monotherapy for the treatment of adult patients with unresectable, locally advanced or metastatic esophageal squamous cell carcinoma (ESCC) after prior platinum-based chemotherapy.

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"Tislelizumab is the first medicine to come from BeiGene’s immuno-oncology research program and our team partnered with patients, caregivers, and clinical researchers across the world to generate the evidence supporting this CHMP recommendation," said Lai Wang, Ph.D., Global Head of R&D at BeiGene. "We continue to make progress in our mission to bring the highest quality therapies to more people around the world and look forward to working with Novartis and health authorities on regulatory filings for tislelizumab."

The Marketing Authorization Application (MAA) for ESCC is based on results from BeiGene’s RATIONALE 302, a global, randomized, open-label, Phase 3 study (NCT03430843) to investigate the efficacy and safety of tislelizumab when compared with investigator’s choice chemotherapy as a second-line treatment for patients with unresectable, locally advanced or metastatic ESCC. The study enrolled 513 patients from 132 research sites in 11 countries in Asia, Europe, and North America. The study met its primary endpoint with a statistically significant and clinically meaningful survival benefit for tislelizumab compared with chemotherapy (HR 0.70 [95%CI 0.57 – 0.85]; one-sided P=.0001; median overall survival 8.6 vs 6.3 months). The safety profile for tislelizumab was consistent with previous trials.i The MAA included safety data for 1,972 patients who received tislelizumab monotherapy in seven clinical trials.

Tislelizumab is not currently authorized for use in Europe.

About ESCCii
Globally, esophageal cancer (EC) is the sixth most common cause of cancer-related deaths and ESCC is the most common histologic subtype, accounting for more than 85% of ECs. An estimated 957,000 new EC cases are projected in 2040, an increase of nearly 60% from 2020 that underscores the need for additional effective treatments.

About Tislelizumab

Tislelizumab is a humanized IgG4 anti-PD-1 monoclonal antibody specifically designed to minimize binding to Fc-gamma (Fcγ) receptors on macrophages, helping to aid the body’s immune cells to detect and fight tumors. In pre-clinical studies, binding to Fcγ receptors on macrophages has been shown to compromise the anti-tumor activity of PD-1 antibodies through activation of antibody-dependent macrophage-mediated killing of T effector cells.

In 2021, BeiGene and Novartis announced a collaboration agreement to jointly develop tislelizumab in the United States, Canada, Mexico, member countries of the European Union, United Kingdom, Norway, Switzerland, Iceland, Liechtenstein, Russia, and Japan. Under the agreement Novartis is responsible for regulatory submission and has the right to commercialize in these licensed countries following regulatory approval.

The EMA is reviewing a MAA for tislelizumab as a treatment for locally advanced or metastatic non-small cell lung cancer (NSCLC) after prior chemotherapy, and in combination with chemotherapy for previously untreated locally advanced or metastatic NSCLC. Regulatory submissions for tislelizumab are also under review by authorities in the U.S., U.K., Australia, China, New Zealand, Brazil, Korea, and Switzerland.

More than 12,000 patients from across the world have participated in the tislelizumab development program that encompasses 21 registration-enabling clinical trials in more than 30 countries and regions. To date, BeiGene has announced positive readouts from 10 Phase 3 pivotal studies across multiple tumor types and disease settings such as NSCLC, Small Cell Lung Cancer, Gastric Cancer, ESCC, Hepatocellular Cancer, and Nasopharyngeal Cancer. More information on the clinical trial program for tislelizumab can be found at: View Source

On July 21, 2023 Novocure (NASDAQ: NVCR) reported the results of a pre-specified interim analysis for the phase 3 PANOVA-3 clinical trial evaluating the safety and efficacy of Tumor Treating Fields (TTFields) therapy together with nab-paclitaxel and gemcitabine for the treatment of patients with unresectable, locally advanced pancreatic cancer (Press release, NovoCure, JUL 21, 2023, View Source [SID1234633372]). An independent data monitoring committee (DMC) reviewed the safety and efficacy data for all patients in the fully enrolled clinical trial. The interim analysis resulted in a DMC recommendation that the clinical trial proceed to final analysis.

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"Completion of the interim analysis with the DMC’s recommendation to continue PANOVA-3 to completion marks another important step in pursuit of our mission to treat patients with difficult solid tumors of the abdomen," said Asaf Danziger, Novocure’s Chief Executive Officer. "I would like to express my thanks to our patients and investigators. We look forward to reviewing the PANOVA-3 data in 2024 and potentially extending the lives of patients diagnosed with deadly locally advanced pancreatic cancer by treating with our novel therapy, Tumor Treating Fields."

About PANOVA-3

PANOVA-3 is a randomized, open-label clinical trial designed to enroll 556 adult patients with unresectable, locally advanced pancreatic adenocarcinoma. Patients have been randomized to receive either the combination of nab-paclitaxel and gemcitabine concomitant with TTFields therapy tuned to 150 kHz until progression or the combination of nab-paclitaxel and gemcitabine alone. The primary endpoint is overall survival. Secondary endpoints include progression free survival, local progression free survival, objective response rate, one-year survival rate, quality of life, pain-free survival, puncture-free survival, resectability rate, and toxicity. Following enrollment of the final patient in February 2023, patients will be followed for a minimum of 18 months.

About Pancreatic Cancer

Pancreatic cancer is one of the most lethal cancers and is the third most frequent cause of death from cancer in the U.S. While overall cancer incidence and death rates are remaining stable or declining, the incidence and death rates for pancreatic cancer are increasing. It is estimated that approximately 53,000 patients are diagnosed with pancreatic cancer each year in the U.S. Pancreatic cancer has a five-year relative survival rate of just 10%.

Physicians use different combinations of surgery, radiation and pharmacological therapies to treat pancreatic cancer, depending on the stage of the disease. For patients with locally advanced pancreatic cancer involving encasement of arteries but no extra-pancreatic disease, the standard of care is surgery followed by chemotherapy with or without radiation. Unfortunately, the majority of locally advanced cases are diagnosed once the cancer is no longer operable, generally leaving chemotherapy with or without radiation as the only treatment option.

About Tumor Treating Fields Therapy

Tumor Treating Fields (TTFields) are electric fields that exert physical forces to kill cancer cells via a variety of mechanisms. TTFields do not significantly affect healthy cells because they have different properties (including division rate, morphology, and electrical properties) than cancer cells. The multiple, distinct mechanisms of TTFields therapy work together to selectively target and kill cancer cells. Due to its multimechanistic actions, TTFields therapy can be added to cancer treatment modalities in approved indications and demonstrates enhanced effects across solid tumor types when used with chemotherapy, radiotherapy, immune checkpoint inhibition, or PARP inhibition in preclinical models. TTFields therapy provides clinical versatility that has the potential to help address treatment challenges across a range of solid tumors. To learn more about Tumor Treating Fields therapy and its multifaceted effect on cancer cells, visit tumortreatingfields.com.

On July 21, 2023 SunHo BioPharmaceutical Co., Ltd. ("SunHo"), a clinical-stage leading biopharmaceutical company in immunocytokines with full-set of capabilities from discovery to commercialization, reported that IBB0979 (B7H3-IL10 immunocytokine), a potential first-in-class immunocytokine developed in-house for the treatment of locally advanced or metastatic solid tumors has entered Phase I/II clinical trials (Press release, SunHo BioPharmaceutical , JUL 21, 2023, View Source [SID1234633371]). The first patient has been dosed on Jul 20th, 2023.

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"We are excited for achieving this important milestone, which also marked the first step to what we hope will ultimately allow us to bring an innovative cancer immunotherapy to patients who otherwise do not respond to or become relapsed/refractory of current therapies", said Dr. Liusong Yin, the Executive Director, Chief Executive Officer and Chief Science Officer of SunHo, "We focus on innovative immunocytokines to build the next leading global biopharma of immunotherapy, and to bring perceivable benefits and affordable medicine to patients worldwide, by innovation and collaboration."

IBB0979 is the world’s first B7H3-IL10 immunocytokine receiving IND approval from both FDA and NMPA, according to Frost & Sullivan. It was developed by SunHo based on their own proprietary and patented Armed ImmunoCytokine ("AIC") platform.

Other two innovative immunocytokines developed based on their proprietary and patented AIC platform, IAP0971(PD1-IL15) and IAE0972(EGFR-IL10) with both U.S. Food and Drug Administration ("FDA") and National Medical Products Administration of People’s Republic of China ("NMPA") investigational new drug ("IND") clearance, are expected to initiate the Phase II clinical trials soon. Phase I clinical data showed that IAP0971 and IAE0972 were well tolerated and demonstrated encouraging preliminary anti-tumor activities in patients with locally advanced or metastatic solid tumors.

On July 21, 2023 Jazz Pharmaceuticals plc (Nasdaq: JAZZ) reported that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion recommending the marketing authorization of JZP458 (a recombinant Erwinia asparaginase or crisantaspase) for use as a component of a multi-agent chemotherapeutic regimen for the treatment of acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) in adult and pediatric patients (1 month and older) who developed hypersensitivity or silent inactivation to E. coli-derived asparaginase (Press release, Jazz Pharmaceuticals, JUL 21, 2023, View Source [SID1234633369]).

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"Today’s positive CHMP opinion is welcome news for those in the ALL and LBL community who are unable to be treated with E. coli-derived asparaginase due to hypersensitivity reactions," says Robert Iannone, MD., M.S.C.E., executive vice president, global head of research and development of Jazz Pharmaceuticals. "We look forward to receiving the final decision that will help bring us one step closer to delivering a reliable supply of recombinant Erwinia asparaginase to patients in the European Union."

The CHMP’s recommendation will now be reviewed by the European Commission (EC), which has the authority to approve medicines in all European Union Member States, Iceland, Norway, and Liechtenstein, and is expected to make a final decision soon.

About Acute Lymphoblastic Leukemia (ALL)
Acute lymphoblastic leukemia (ALL) is a cancer of the blood and bone marrow that can progress quickly if not treated.1,2 ALL is the most common childhood malignancy, accounting for 80% of leukemia diagnoses in children, compared to 20% of adults.3 Long-term survival rates for pediatric patients have improved significantly over the last few decades.4 The estimated overall incidence of ALL and lymphoblastic lymphoma (LBL) in Europe is 1.28 per 100,000.5

Asparaginase is a core component of multi-agent chemotherapeutic regimens in ALL,6 however, up to 30% of patients develop hypersensitivity to E. coli-derived asparaginase,7 necessitating treatment discontinuation or a switch to a non-E. coli-derived asparaginase preparation.8 Patients not receiving asparaginase due to hypersensitivities and those not receiving all prescribed doses have been shown to have poor outcomes.9,10

About Lymphoblastic Lymphoma (LBL)
Lymphoblastic Lymphoma (LBL) is a rare, fast-growing, aggressive subtype of non-Hodgkin’s lymphoma (NHL), which is very rare in adults and is most often seen in teenagers and young adults under the age of 35.11,12 LBL is a type of high-grade lymphoma – which means the lymphoma grows quickly with early spread to different parts of the body.12 LBL is the second most common type of NHL in childhood and adolescence, accounting for 25-35% of cases.13

About JZP458
JZP458 is a recombinant Erwinia asparaginase or crisantaspase that uses a Pseudomonas fluorescens expression platform.9 It is being developed for use as a component of a multi-agent chemotherapeutic regimen in the treatment of pediatric and adult patients with acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) who developed hypersensitivity to E. coli-derived asparaginase products. JZP458 was approved by the U.S. Food and Drug Administration (FDA) in June 2021 for the treatment of this patient population and became commercially available in July of the same year in the U.S.