On July 18, 2022 MEI Pharma, Inc. (NASDAQ: MEIP), a late-stage pharmaceutical company focused on advancing new therapies for cancer, and Kyowa Kirin Co., Ltd. (Kyowa Kirin, TSE: 4151), a global specialty pharmaceutical company creating innovative medical solutions utilizing the latest biotechnology, reported that publication of data from the Phase 1b clinical study of zandelisib, an orally administered investigational phosphatidylinositol 3-kinase delta ("PI3Kδ") inhibitor, in patients with relapsed or refractory (R/R) B-cell malignancy in The Lancet Oncology (Press release, MEI Pharma, JUL 18, 2022, View Source [SID1234616737]). The published data demonstrate that an intermittent dosing regimen of zandelisib resulted in lower cumulative risk of Grade 3 or worse adverse events of special interest compared to a continuous daily dosing regimen without loss of efficacy. The publication, entitled "Zandelisib with continuous or intermittent dosing as monotherapy or in combination with rituximab in patients with relapsed or refractory B-cell malignancy: a multicentre, first-in-patient, dose-escalation and dose-expansion, phase 1b trial," is available on the journal website.

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"The results observed in our Phase 1b study reinforce the potential of zandelisib, an investigational clinical candidate, to provide a well-tolerated clinical profile either as a single-agent or in combination with other therapies without a loss of efficacy via a unique intermittent schedule compared to continuous daily dosing," said Richard Ghalie, M.D., chief medical officer of MEI Pharma. "We remain encouraged by zandelisib’s potential as we continue its development using the intermittent schedule as an oral, chemotherapy-free, time-limited, therapeutic option to meet the needs of patients."

"Based on the results of the Phase 1b study, zandelisib could establish a potential alternative to chemotherapy with a unique dosing schedule for this class, both as a single agent and in combination with other drugs," said Yoshifumi Torii, Ph.D., Executive Officer, Vice President, Head of R&D Division of Kyowa Kirin. "We will continue to work with MEI to develop new treatment options for patients with B-cell malignancies."

The Phase 1b study (NCT02914938) is an open-label, dose escalation and expansion study evaluating zandelisib in patients with B-cell malignancies. The manuscript reported on a total of 97 patients, including 31 patients in the dose escalation stage that established 60 mg once daily as the recommended Phase 2 dose. The study evaluated zandelisib in 56 patients as a monotherapy and 41 patients in combination with rituximab. Zandelisib was administered either on a continuous schedule of 60 mg once daily (n=38) or an intermittent dosing schedule of 60 mg once daily for the initial two 28-day cycles followed by the intermittent dosing (ID) schedule of 60 mg once daily on days 1-7 in cycles ≥3 (n=59).

In the initial monotherapy dose-finding part of the study, no dose-limiting toxicities were observed across the evaluated doses of 60 mg, 120 mg and 180 mg given daily continuously, and anti-tumor activity was similar across doses. With a median duration of treatment of 10.4 months and 15.2 months, in the continuous and intermittent dosing group respectively, Grade 3 or worse adverse events of special interest occurred less frequently in the intermittent dosing group than in the continuous dosing group. For example, Grade 3 diarrhea or colitis in 8% vs 24%, and Grade 3 lung infection or pneumonia in 2% vs 16%, of patients in the intermittent dosing group vs the continuous dosing group, respectively. Grade 3 or worse AST or ALT elevation (5%) and rash (5%) were uncommon with each dosing schedules. There was a continued increased risk of Grade 3 diarrhea or colitis in the continuous dosing group, compared with a decreased risk over time in the intermittent dosing group after switching to the intermittent dosing. At a median follow-up of 24.9 months in the continuous dosing group and 15.7 months (95% CI 6·5-33·9) in the intermittent dosing group the cumulative incidence of Grade 3 or worse adverse events of special interest was 45% in the continuous dosing group and 20% in the intermittent dosing group.

Intermittent dosing showed comparable efficacy to continuous dosing. Patients with indolent B-cell malignancies (follicular lymphoma, chronic lymphocytic leukemia or small lymphocytic lymphoma, and marginal zone lymphoma) demonstrated an objective overall response rate of 87%.

The published Phase 1b safety and efficacy results for zandelisib 60 mg once daily on an intermittent dosing schedule warranted initiating the ongoing global Phase 2 TIDAL and Phase 3 COASTAL studies evaluating zandelisib alone or in combination with rituximab, respectively.

About Zandelisib

Zandelisib, a selective PI3Kδ inhibitor, is an investigational cancer treatment being developed as an oral, once-daily, potential therapeutic option for patients with B-cell malignancies. Clinical trials are investigating the efficacy and safety of zandelisib as a single agent and in combination with other modalities while administered on an Intermittent Dosing Regimen (ID) and in a time-limited manner when dosed in combination. The ID leverages molecular and biologic properties specific to zandelisib.

Ongoing zandelisib studies include the cohort in TIDAL evaluating patients with r/r marginal zone lymphoma (MZL) and continuing evaluation of the cohort of patients in the study with r/r FL. Also ongoing is the Phase 3 COASTAL study (NCT04745832), comparing zandelisib plus rituximab to standard of care chemotherapy plus rituximab in patients with r/r FL or MZL who received more than one prior line of therapy, which must have included an anti-CD20 antibody in combination with chemotherapy or lenalidomide. COASTAL, which is also evaluating time-limited intermittent administration of zandelisib, is intended to support marketing applications in the U.S. and globally.

Other ongoing studies include a Phase 2 pivotal study in Japan (NCT04533581) in patients with indolent B-cell non-Hodgkin’s lymphoma (iB-NHL) without small lymphocytic lymphoma (SLL), lymphoplasmacytic lymphoma (LPL), and Waldenström’s macroglobulinemia (WM) conducted by Kyowa Kirin.

In March 2020, the FDA granted zandelisib Fast Track designation for the treatment of adult patients with r/r follicular lymphoma who have received at least two prior systemic therapies. In November 2021, the FDA granted zandelisib Orphan Drug designation for the treatment of patients with follicular lymphoma.

In April 2020, MEI and Kyowa Kirin entered a global license, development, and commercialization agreement to further develop and commercialize zandelisib. MEI and Kyowa Kirin will co-develop and co-promote zandelisib in the U.S., with MEI booking all revenue from the U.S. sales. Kyowa Kirin has exclusive commercialization rights outside of the U.S.

On July 18, 2022 MAIA Biotechnology, Inc., a targeted therapy, immuno-oncology company focused on developing potential first-in-class oncology drugs ("MAIA"), reported that the first patient has been dosed in MAIA’s Phase 2 clinical trial, THIO-101, evaluating the administration of THIO, in sequence with cemiplimab, in patients with advanced Non-Small Cell Lung Cancer (NSCLC) (Press release, MAIA Biotechnology, JUL 18, 2022, View Source [SID1234616736]).

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The THIO-101 Phase 2 trial is designed to evaluate THIO’s potential immune system activation effects in NSCLC patients by administering THIO in advance of administration of the checkpoint inhibitor cemiplimab (developed by Regeneron), allowing for immune activation and PD-1 sensitivity to take effect. The primary objectives of the trial are to evaluate the safety and tolerability of THIO administered as a direct anticancer and priming immune system agent prior to cemiplimab administration, as well as the clinical efficacy of THIO in patients with advanced NSCLC who either progressed or relapsed through treatment with an immune-check point inhibitor alone or in combination with chemotherapy. The first patient in THIO-101 was dosed in Australia in July 2022 after the Company’s application received regulatory approval in March 2022. The Company also plans to submit a similar application in the second quarter of 2022, to conduct the same Phase 2 study in Europe.

"Dosing our first patient in this Phase 2 trial with THIO is an important milestone for MAIA, marking the continued development of our telomere-targeting approach," said Vlad Vitoc, M.D., MAIA’s Chairman and Chief Executive Officer. "Despite the advancements made in the field with checkpoint inhibitors, monoclonal antibodies and newer immunotherapies, very limited treatment options exist for patients that have progressed beyond the standard-of-care regimens. We believe THIO has the potential to hold a significant place in the NSCLC treatment paradigm."

Sergei Gryaznov, Ph.D., Chief Scientific Officer of MAIA, added, "Lung cancer is the second most diagnosed cancer worldwide and NSCLC is the most common form of lung cancer, accounting for more than eighty percent of all lung cancer diagnoses. This represents a significant unmet medical need across the globe, and we remain enthusiastic about THIO’s observed mechanism of action."

About THIO-101, a Phase 2 Clinical Trial

THIO-101 is a multicenter, open-label, dosing finding Phase 2 clinical trial. It is the first trial designed to evaluate THIO’s potential immune system activation effects in NSCLC patients by administering THIO in advance of administration of the checkpoint inhibitor cemiplimab (developed by Regeneron), potentially allowing for immune activation and PD-1 sensitivity to take effect. The trial will test the hypothesis that low doses of THIO administered prior to checkpoint inhibitor treatment will enhance and prolong immune response in patients with advanced NSCLC who previously did not respond or progressed after first-line treatment regimen containing a checkpoint inhibitor. The trial design has two primary objectives: (1) to evaluate the safety of THIO administered as an anticancer agent and a priming immune system agent prior to cemiplimab administration and (2) to assess the clinical efficacy of THIO followed by cemiplimab using Overall Response Rate (ORR) as the primary clinical endpoint. For more information on this Phase II trial, please visit ClinicalTrials.gov using the identifier NCT05208944.

About THIO

THIO (6-thio-dG or 6-thio-2’-deoxyguanosine) is an investigational telomere-targeting agent currently in clinical development to evaluate its activity in NSCLC. Telomeres, along with the enzyme telomerase, play a fundamental role in the survival of cancer cells and their resistance to current therapies. THIO is being developed for patients with NSCLC that have progressed beyond the standard-of-care regimen of existing checkpoint inhibitors.

On July 18, 2022 Nuvation Bio Inc. (NYSE: NUVB), a biopharmaceutical company tackling some of the greatest unmet needs in oncology by developing differentiated and novel therapeutic candidates, reported the appointment of David Liu, M.D., Ph.D., as Chief Medical Officer and Kerry Wentworth as Chief Regulatory Officer (Press release, Nuvation Bio, JUL 18, 2022, View Source [SID1234616735]). Dr. Liu will lead Nuvation Bio’s clinical development team and collaborate with the executive committee to provide strategic direction for the Company’s research and drug development programs. Ms. Wentworth will oversee regulatory and quality affairs across the Company’s pipeline.

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"I am honored to join Nuvation Bio and oversee the clinical development of innovative therapies for the most difficult-to-treat cancers," said Dr. Liu. "I look forward to working with this experienced and dedicated team to address the unmet needs of cancer patients."

"Nuvation Bio’s mission to bring meaningful cancer treatments to patients who have nearly exhausted all options deeply resonates with me," said Ms. Wentworth. "The Company is taking on this bold challenge with tenacity and urgency, and I am proud to contribute to this important work."

Dr. Liu brings over 20 years of experience leading the discovery and development of oncology therapies, including New Drug Application (NDA) submissions for multiple oncology assets in the U.S., Europe, and China. Most recently, Dr. Liu served as the Chief Medical Officer at a biotechnology company based in Shanghai, China. There, he built and led their clinical research and development organization, including global clinical research, global clinical operations, pharmacovigilance, biostatistics, programming and data management, clinical pharmacology, and drug supply.

Ms. Wentworth has over 25 years of experience in domestic and international regulatory and quality affairs. Her background spans early and late development across multiple therapeutic areas, including oncology, osteoarthritis, pain management, autoimmune disorders, and rare diseases. She also has a broad scope of product knowledge, ranging from injectable small molecules to complex autologous platforms. Ms. Wentworth most recently served as Chief Regulatory Officer at Flexion Therapeutics, which was acquired by Pacira Biosciences in 2021, setting and delivering on regulatory and quality strategies across their product portfolio. Notably, Ms. Wentworth was instrumental in leading the company’s first NDA successfully into commercialization.

"We are pleased for David and Kerry to join the Nuvation Bio team and believe their decades of focused experience at leading global biopharmaceutical companies will significantly contribute to the development of our various programs," said David Hung, M.D., Founder, President, and Chief Executive Officer of Nuvation Bio. "We look forward to working with them as we aim to meaningfully improve the lives of cancer patients."

Earlier in his career, Dr. Liu held several roles of increasing strategic responsibility at Bristol Myers Squibb, where he became a leader in Oncology Global Clinical Research, including leading the Global Prostate Cancer Program, Pediatric Clinical Development, and Translational Research for ipilimumab, and development of nivolumab and ipilimumab for China. After Bristol Myers Squibb, Dr. Liu was the Global Lead Physician at Celgene for the revlimid plus rituximab submission program in indolent lymphoma. Dr. Liu earned a Ph.D. from the Massachusetts Institute of Technology, an M.S. from the University of Toledo, and an M.D. from Beijing Medical University (Peking University School of Medicine).

Prior to joining Flexion, Ms. Wentworth served as Vice President, Clinical, Regulatory, and Quality at Agenus, Inc., where she led all global regulatory and clinical development efforts. Previously, Ms. Wentworth led the regulatory and quality function for Genelabs Technologies, Inc., and prior to that held positions of increasing responsibility within Regulatory Affairs at Genzyme. Ms. Wentworth holds a B.S. in pre-veterinary medicine from the University of New Hampshire.

On July 18, 2022 Tiziana Life Sciences Ltd. (Nasdaq: TLSA) ("Tiziana" or the "Company"), a biotechnology company enabling breakthrough immunotherapies via novel routes of drug delivery, reported that it has appointed Matthew Davis, MD, RPh as its Chief Medical Officer and Acting Chief Scientific Officer, effective immediately (Press release, Tiziana Life Sciences, JUL 18, 2022, View Source [SID1234616734]). Dr. Davis will report to Gabriele Cerrone, Executive Chairman and interim Chief Executive Officer of Tiziana.

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"Dr. Davis is a proven leader with 25 years in the pharmaceutical industry," said Gabriele Cerrone, Tiziana’s Executive Chairman and interim Chief Executive Officer. "We believe Dr. Davis’ experience with drug approvals is a key asset as the Company focuses more of its resources from discovery to proof-of-concept clinical trials. His broad therapeutic and FDA expertise, along with his in-depth experience with biologics will be invaluable as we pursue our mission to bring breakthrough therapies with the aim of treating Secondary-Progressive Multiple Sclerosis (SPMS), Crohn’s Disease and KRAS+ NSCLC and optimizing health outcomes."

"I am thrilled to join the Tiziana team, and for the opportunity to help advance Foralumab, TZLS-501 and Milciclib. I am energized to work with the passionate and dedicated R&D team and to meet the prestigious Scientific Advisors who are helping to guide the company," said Matthew W Davis, MD, RPh.

Dr. Davis has extensive experience in new drug application, or NDA, and biologic license application, or BLA, FDA approvals and device clearances. Notable approved brands that Dr. Davis has worked on include Lidoderm, Sculptra, Colcrys and most recently QWO.

Dr. Davis previously served as Chief Scientific Officer and Chief Medical Officer at Endo Pharmaceuticals where he restructured the R&D department and collaborated to obtain BLA approval for QWO. Additionally, Dr. Davis was Chief Medical Officer for Lupin Inc. and URL Pharma, Inc. where he spearheaded three NDA approvals and was the inventor on all 17 Orange Book listed patents for Colcrys. He also was on the executive team that sold URL Pharma to Takeda Pharmaceutical Company for approximately $800M combined with over $1B in performance-based contingent earn out payments.

Dr. Davis matriculated to the University of Pennsylvania as an undergraduate. He received his Pharmacy Degree from Temple University and his Medical Degree from the Medical College of Pennsylvania. Dr. Davis undertook his surgical training at Brown University and his Urology training at Washington Hospital Center.

On July 18, 2022 PharmaMar (MSE:PHM) reported that its partner in China, Luye Pharma Group Ltd., has obtained permission from the Hainan health authorities to open a compassionate use program for lurbinectedin for the treatment of Small Cell Lung Cancer ("SCLC") (Press release, PharmaMar, JUL 18, 2022, View Source [SID1234616733]).

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Lung cancer is a malignant tumor with high morbidity and mortality rates in China, and SCLC is an aggressive high-grade neuroendocrine carcinoma that accounts for 13%–17% of all lung cancer cases. According to the International Agency for Research on Cancer ("IARC"), lung cancer had higher morbidity and mortality rates than other malignant tumors in China in 2020, with 815,000 new lung cancer cases and 714,000 deaths reported that year. The IARC also predicted that in 2022 the number of new SCLC cases in China will exceed 110,000.

The opening of an Expanded Access Program for lurbinectedin to be used in Hainan means that Luye Pharma Group Ltd will be the first company to bring a new treatment option to SCLC patients in China who urgently need effective treatments.

In June 2020, lurbinectedin received "Accelerated Approval" from the FDA for the treatment of adult patients with metastatic SCLC with disease progression and is already the standard of care in the US. Lurbinectedin has also received marketing authorization in the United Arab Emirates, Canada, Australia and Singapore, and more recently in Qatar.