On June 18, 2020 Ascentage Pharma (6855.HK), a globally focused, clinical-stage biotechnology company engaged in developing novel therapies for cancers, chronic hepatitis B (CHB), and age-related diseases, reported that Guangzhou Healthquest Pharma Co., Ltd, a wholly-owned subsidiary of Ascentage Pharma’s, has submitted a New Drug Application (NDA) to the Center for Drug Evaluation (CDE) of China National Medical Products Administration (NMPA) for HQP1351 for the treatment of patients with T315I-mutant chronic phase chronic myeloid leukemia (CP-CML) and accelerated phase CML (AP-CML) (Press release, Ascentage Pharma, JUN 18, 2020, View Source [SID1234561220]). This is Ascentage Pharma’s first NDA submission since its inception. If approved, HQP1351 will become the first third-generation BCR-ABL inhibitor therapeutics in China.

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Ascentage Pharma recently engaged in pre-NDA discussions with the CDE regarding the NDA based on results from two pivotal studies in patients with T315I-mutant CP-AML and AP-CML. The CDE has agreed that the company should proceed to submit the NDA for those two indications.

CML is a hematologic malignancy of the white blood cells. BCR-ABL tyrosine kinase inhibitors (TKI) have significantly improved the clinical management of CML. However, despite clinical benefits offered by the first-generation BCR-ABL inhibitor imatinib (GLEEVEC), and several second-generation TKIs, acquired resistance to TKIs remains a major challenge in the treatment of CML. BCR-ABL tyrosine kinase mutations represent a key mechanism of acquired drug resistance; T315I, which is the most common drug-resistant mutation, occurs in about 25% of patients with drug-resistant CML. Patients with T315I-mutant CML are resistant to both first- and second-generation BCR-ABL inhibitors, hence presenting an urgent unmet medical need for effective treatment.

HQP1351 is a novel, orally active, potent third-generation BCR-ABL inhibitor designed to effectively target BCR-ABL mutants, including T315I, and the first China-developed third-generation BCR-ABL inhibitor targeting drug-resistant CML. In July 2019, HQP1351 was cleared by the US Food and Drug Administration (FDA) to enter a Phase Ib clinical study. In May 2020, HQP1351 was granted an Orphan Drug Designation and a Fast Track Designation by the US FDA.

"As Ascentage Pharma’s first NDA and one that may lead to the market authorization of the first third-generation BCR-ABL inhibitor in China, this submission marks a major milestone for our company," said Dr. Dajun Yang, Chairman & CEO of Ascentage Pharma. "For patients with CML who cannot be effectively treated by currently available TKIs, there remains an urgent unmet medical need for safer and more effective therapies. We hope that HQP1351 will bring a breakthrough to the current conundrum and benefit more patients."

On June 18, 2020 NantHealth, Inc. (NASDAQ: NH), a next-generation, evidence-based, personalized healthcare company, reported the publication of four abstracts on developmental therapeutics for immunotherapy, molecularly targeted agents and tumor biology during the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2020 Virtual Scientific Program (Press release, NantHealth, JUN 18, 2020, View Source [SID1234561219]).

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The program, held virtually from May 29-31, 2020, gathered oncology physicians, biotechnology executives, researchers, patient advocates, and investment analysts to discuss cutting-edge clinical research and therapeutics in oncology, and to gain insights for improving cancer care.

Alongside ImmunityBio, LLC, and others, Dr. Sandeep K. Reddy, Chief Medical Officer at NantHealth, and Christopher Szeto, Director of Machine Learning at NantHealth, presented the data gathered from NantHealth’s database which was used to advance findings in developmental therapeutics.

The details of NantHealth’s ASCO (Free ASCO Whitepaper) posters are as follows:

Title: "Effect of chemokine signaling signatures on resolving discrepancy between TMB and checkpoint expression"
Authors: Saihitha Veerapaneni, Rahul Parulkar, Sandeep K. Reddy, Shahrooz Rabizadeh, Stephen Charles Benz and Christopher Szeto; ImmunityBio, LLC, Culver City, CA; NantHealth, Culver City, CA
Abstract Number: 3131
Session Title: Developmental Therapeutics—Immunotherapy

"In this study, 1,395 clinical samples from the NantHealth database with matched tumor normal whole exomes and deep whole-transcriptomic sequencing were analyzed to confirm previous findings that Tumor Mutation Burden (TMB) and PDL1 mRNA were not correlated," said Dr. Sandeep K. Reddy, Chief Medical Officer, NantHealth. "However, chemokine activity may be an alternative to TMB and PDL1 to identify patients appropriate for immunotherapy and can help resolve discordant cases."

Title: "Targetable immune checkpoint molecules may be significantly differentially expressed in minority ethnicities"
Authors: Jacob J. Adashek, Christopher Szeto, J. Zack Sanborn, Sandeep K. Reddy, Amir A. Toor, Stamatina Danielides, Steven Smith, Steven R. Grossman, Charles V Clevenger, Anthony Faber, Andrea Ferreira-Gonzalez, Sosipatros Alexandros Boikos; University of South Florida, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL; NantHealth, Culver City, CA
Abstract Number: 3576
Session Title: Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology

"The Cancer Genome Atlas (TCGA) data for 7,087 patients and about 2,700 patients in the NantHealth database were used to identify differential patterns of checkpoint gene expression across different ethnic groups," said Dr. Sandeep K. Reddy, Chief Medical Officer, NantHealth. "White breast cancer patients might be anticipated to exhibit reduced sensitivity to PD1/CTLA4 blockade, while Black colon cancer patients may exhibit reduced sensitivity to IDO1 therapies, such as epacadostat. Ethnicity may represent a significant factor for efficacy checkpoint blockade therapies."

Title: "Highly accurate automated tissue classification using deep learning on digital pathology images: A novel tool for resolving conflicts in diagnosis"
Authors: Liudmila Beziaeva, Mustafa Jaber, Stephen Charles Benz, Shahrooz Rabizadeh, and Christopher Szeto, ImmunityBio, LLC, Culver City, CA; NantHealth, Culver City, CA
Abstract Number: 3578
Session Title: Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology

"NantHealth combined whole slide imaging with deep neural networks to develop a tool which can identify which of 24 primary tumor types a sample is derived from with 94.6 percent accuracy," said Christopher Szeto, Director of Machine Learning, NantHealth. "This accuracy, which approaches that of a human pathologist, is achieved by focusing machine-vision attention on just tumor regions within bulk samples. Used in conjunction with molecular profiling, rates of Cancers of Unknown Primary (CUP) or misdiagnosis can feasibly be minimized to improve patient care."

Title: "High correlation between TMB, expressed TMB, and neoantigen load using tumor: Normal whole exome DNA and matched whole transcriptome RNA sequencing"
Authors: Christopher Szeto, Mrinal M. Gounder, Rahul Parulkar, Andrew Nguyen, Shahrooz Rabizadeh, Sandeep K. Reddy; Memorial Sloan Kettering Cancer Center, New York, NY; ImmunityBio, LLC, Culver City, CA; NantHealth, Culver City, CA
Abstract Number: e15238
Session Title: Publication Only: Developmental Therapeutics—Immunotherapy

"Surprisingly, we see minimal difference between the various biomarkers derived from mutational burden," said Christopher Szeto, Director of Machine Learning, NantHealth. "Tissue-specific TMB thresholds may be useful in patient with Sarcoma and Pancreatic cancers. Otherwise, additional data inputs such as microbiome, chemokine expression, and TME cell phenotyping may be required to improve upon TMB as a biomarker of immunotherapy response."

On June 18, 2020 Sermonix Pharmaceuticals Inc., a privately held biopharmaceutical company focused on the development of female-focused oncology products in the precision medicine metastatic breast cancer arena, reported that it will share a poster and audio presentation on its lead investigational drug, lasofoxifene, for the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting II (Press release, Sermonix Pharmaceuticals, JUN 18, 2020, View Source [SID1234561218]).

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The abstract compares the efficacy of lasofoxifene, a selective estrogen receptor modulator (SERM), and CDK 4/6 inhibitor palbociclib combinations to that of fulvestrant, a selective estrogen receptor degrader (SERD), and palbociclib combinations in NSG mice with breast tumors carrying Y537S ESR1 mutations.

Presentation Details:
Title: "Lasofoxifene Alone or in Combination With Palbociclib as an Effective Treatment for Therapy-Resistant ER+ Metastatic Breast Cancer"
Session: PO.EN02.01 – Molecular, Preclinical, and Clinical Endocrinology 2
Abstract ID: 4370/ 13
Date + Time: June 22 from 9 a.m. EDT to 6 p.m.

Following the virtual presentation, the poster will be available in the Medical Meetings section of the Sermonix Pharmaceuticals website.

"The results demonstrate a positive, synergistic efficacy of lasofoxifene with a CDK 4/6 inhibitor, supporting this type of combination therapy approach in clinical studies," said David Portman, Sermonix founder and chief executive officer. "We look forward to detailing these new results during this important AACR (Free AACR Whitepaper) online gathering of the oncology community and initiating a Phase 2 combination study in the near future."

The study was conducted by the University of Chicago’s Ben May Department for Cancer Research.

"This work marks an important step in continuing to build the foundation of our ongoing, robust ELAINE clinical development program," said Beth Attias, Sermonix chief strategy and development officer. "We are grateful for the collaboration with the University of Chicago and this groundbreaking work of Dr. Geoffrey Greene."

About Lasofoxifene
Lasofoxifene is an investigational, nonsteroidal selective estrogen receptor modulator (SERM), which Sermonix licensed from Ligand Pharmaceuticals Inc. (NASDAQ: LGND) and has been studied in previous comprehensive Phase 1-3 non-oncology clinical trials in more than 15,000 postmenopausal women worldwide. Lasofoxifene’s bioavailability and activity in mutations of the estrogen receptor could potentially hold promise for patients who have acquired endocrine resistance due to ESR1 mutations, a common finding in the metastatic setting and an area of high unmet medical need. Lasofoxifene’s novel activity in ESR1 mutations was discovered at Duke University and Sermonix has exclusive rights to develop and commercialize the product in this area. Lasofoxifene, a potent, oral SERM could, if approved, play a critical role in the targeted precision medicine treatment of advanced ER+ breast cancer.

On June 18, 2020 Lyell Immunopharma ("Lyell") and PACT Pharma ("PACT") reported a strategic partnership to jointly develop and test a next generation personalized anti-cancer T cell therapy against solid tumors (Press release, PACT Pharma, JUN 18, 2020, View Source [SID1234561217]).

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The partnership combines technologies to develop a personalized T cell therapy using patients’ own T cells through non-viral precision genome engineering for tumor neoantigen specificity while overcoming potential tumor resistance and T cell exhaustion in treating patients with solid cancers.

"Current T cell therapies for patients with solid tumors face hurdles of target specificity and cell functionality that this partnership is committed to overcome," said Alex Franzusoff, Ph.D., CEO of PACT. "Our goal is to engineer and develop transformational and curative product candidates for patients with solid tumors by addressing these hurdles together, for each patient. We believe this multi-faceted approach has the potential to deliver the greatest patient benefit."

"By combining efforts in this way, PACT and Lyell are leveraging the best technologies on both sides of the T cell specificity-functionality equation," said Rick Klausner, M.D., CEO of Lyell. "More than a technological partnership, this is an opportunity to leverage decades of expertise from some of the field’s best minds, which is very exciting to all of us."

"To efficiently fight solid tumors, neoantigen-targeted T cells will encounter adverse tumor environments and must not be turned off by the cancer," said Antoni Ribas, M.D., Ph.D., co-founder at PACT. "The world-leading scientists at Lyell have designed original strategies to enhance T cell persistence and tumor-killing activity. With PACT’s ability to specifically redirect T cells to mutations in cancer, I believe this partnership will significantly advance the pursuit of highly targeted and effective personalized T cell therapies."

"PACT has sophisticated technologies enabling the first evaluations of personalized adoptive T cell therapy in clinical trials for common solid tumors targeting conserved mutations in the patient’s cancer," said Stanley Riddell, M.D., Head of Research and Development at Lyell. "We are excited by the opportunity to work together to accelerate clinical evaluation of a next generation cellular therapy that is designed to sustain the function of T cells at tumor sites."

The Program resulting from the partnership, which includes upfront and milestone payments to PACT, will be jointly owned and each party will share profits equally if successful. PACT and Lyell will each continue to pursue programs independently and through their other partnerships.

On June 18, 2020 Cambrex, the leading small molecule company providing drug substance, drug product and analytical services across the entire drug lifecycle, reported that Tom Loewald has been named Chief Executive Officer and a member of the company’s Board of Directors, effective September 7th (Press release, Cambrex, JUN 18, 2020, View Source [SID1234561213]). As previously announced, in the interim, the company will be led by an Office of the CEO comprised of Wayne Hewett, Chairman of the Board, Robert Green, Executive Vice President and Chief Financial Officer, and Samantha Hanley, Senior Vice President and General Counsel.

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Mr. Loewald is a 15-year veteran of Thermo Fisher Scientific, where he served in several senior executive roles during his tenure, including Chief Commercial Officer, President of the Analytical Instruments Group, President of the Laboratory Products Group and President of the Laboratory Equipment Division. He currently serves as President of the Flexibles Division of ProAmpac, a leading flexible packaging manufacturer. Earlier in his career he held leadership positions at Tyco International and General Electric. Mr. Loewald currently serves on the Board of Directors of Harvard BioScience, a global developer, manufacturer and marketer of a broad range of solutions to advance life science.

"Cambrex has a phenomenal reputation for providing unmatched expertise, innovation and customer service across the entire drug lifecycle, and I am thrilled to be joining the company at a time when bringing therapeutics to patients across the globe is more important than ever," said Mr. Loewald. "I am eager to get to work, alongside the talented leadership team, to further solidify the company’s position as a leader in the CDMO market."

Wayne Hewett, Chairman of the Board of Directors, said, "Tom’s deep knowledge of life sciences and manufacturing, and strong commercial, operating and financial focus, make him the ideal leader for Cambrex as we approach this phase of accelerated growth. We are confident that he will be an excellent fit for the company’s customer-centric culture and look forward to supporting him and the entire team on the exciting road ahead."