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CytoImmune Not Affected by The Recent Challenges in Allogeneic CAR T Cell Engineering

On October 17, 2021 CytoImmune Therapeutics, Inc. ("CytoImmune"), a clinical-stage immunotherapy company, reported that believes its strategic plan not affected by the recent developments around Allogene Therapeutics’ AlloCAR T (Press release, CytoImmune Therapeutics, OCT 17, 2021, View Source [SID1234591776]). CytoImmune’s approach to NK cell immunotherapy does not involve lentiviral transduction or gene editing.

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On October 7th 2021, Allogene Therapeutics reported an FDA clinical hold on its AlloCAR T trials based on a single patient case in its ALPHA2 trial. Assessment of a patient with low blood counts showed a clonal chromosomal abnormality in ALLO-501A CAR T cells of unclear clinical significance. ALLO-501A is an anti-CD19 AlloCAR T which entered Phase 1/2 study in June 2020. ALLO-501A is a T cell product that has undergone lentiviral transduction for expression of its chimeric antigen receptor (CAR) and two rounds of gene editing to knock out the T-cell receptor as well as expression of CD52. The cause of the chromosomal abnormality found in the patient’s ALLO-501A CAR T cells is currently under investigation.

In contrast, CytoImmune is developing a novel class of allogeneic, off-the-shelf natural killer (NK) cell-based immunotherapies engineered to eliminate cancer cells using well-established retroviral transduction technology without the use of gene editing technologies. Our NK cell engineering platform builds on our founders 54 years of collective laboratory investigation of NK cells, their treatment of over 1,000 patients with therapies modulating NK cells in man, and their extensive history of transducing human NK cells to assess gene function.

Our current platforms include proprietary technologies that enable us to: (1) generate an abundant supply of potent human CAR NK cells to treat multiple patients from a single umbilical cord blood product, (2) undertake highly efficient retroviral transduction of the CAR and/or secreted bispecific killer cell engagers into human NK cells, (3) improve the persistence of these CAR NK cells for sustained activity once infused into the body, (4) freeze, store and thaw our CAR NK cells to be infused as an unmatched, allogeneic off-the-shelf treatment of cancer.

CytoImmune continues to advance its NK cell-based platform toward the clinic with patient safety as our highest priority.

Innovent Announces ORIENT-31, a Phase 3 Study of Sintilimab in Patients with EGFR-Mutated Nonsquamous Non-Small Cell Lung Cancer with Prior EGFR-TKI Treatment, Has Met Primary Endpoint

On October 17, 2021 Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high quality medicines for the treatment of oncology, metabolic, autoimmune and other major diseases, reported that the sintilimab ORIENT-31 study has met its prespecified primary endpoint of progression-free survival (PFS) at the first interim analysis (Press release, Innovent Biologics, OCT 17, 2021, View Source [SID1234591407]).

Globally, ORIENT-31 is the first prospective, double-blind, multi-center, Phase 3 study that has demonstrated significant PFS improvement of anti-PD-1 and anti-VEGF antibody combination therapy (i.e., sintilimab plus BYVASDA [bevacizumab biosimilar injection] combined with chemotherapy [pemetrexed and cisplatin]) in patients with epidermal growth factor receptor (EGFR)-mutated nonsquamous non-small cell lung cancer (nsqNSCLC) that has progressed after treatment with an EGFR tyrosine kinase inhibitor (TKI).

In the first interim analysis reviewed by the Independent Data Monitoring Committee (IDMC), in the intent-to-treat (ITT) population, based on assessment by the Blinded Independent Radiographic Review Committee (BIRRC), sintilimab in combination with BYVASDA (bevacizumab biosimilar injection) and chemotherapy demonstrated a statistically significant and clinically meaningful improvement in PFS compared with chemotherapy. Sintilimab in combination with chemotherapy also showed a trend of PFS benefit compared to chemotherapy alone (data is not yet mature). Additionally, the prespecified PFS futility analysis that compares sintilimab in combination with BYVASDA (bevacizumab biosimilar injection) and chemotherapy to sintilimab in combination with chemotherapy did not cross futility stopping boundary. A numerical benefit of adding BYVASDA (bevacizumab biosimilar injection) to sintilimab and chemotherapy combination can be observed. The safety profile of this study was consistent with that observed in previously reported studies of sintilimab and BYVASDA (bevacizumab biosimilar injection), with no additional safety signals. The detailed results of ORIENT-31 will be presented at an upcoming medical meeting.

The principal investigator of the ORIENT-31, Prof. Shun Lu from the Oncology Department of Shanghai Chest Hospital, stated, "For patients with EGFR-mutated advanced nsqNSCLC who have progressed following EGFR-TKI treatment, platinum-based chemotherapy is the current standard of care, but with limited benefit. New treatments are clearly imperative. ORIENT-31 is the first prospective, double-blind Phase 3 study worldwide to demonstrate significant PFS benefit with an anti-PD-1 antibody combination therapy in this patient population. It has shown the clinical value of adding sintilimab plus BYVASDA (bevacizumab biosimilar injection) to platinum chemotherapy. This quadruple regimen has the potential to bring forth a new and more effective treatment option to patients with EGFR-mutated nsqNSCLC following treatment with an EGFR TKI."

Dr. Hui Zhou, Senior Vice President of Innovent, stated, "Lung cancer has the highest mortality rate among all tumor types both in China and worldwide. In China, EGFR-mutated NSCLC accounts for 40% to 50% of nonsquamous NSCLC, and the treatment options for these patients after treatment with first, second and third generation EGFR-TKIs are very limited, representing a large unmet medical need. Through the joint efforts of investigators, ORIENT-31 achieved these encouraging research results. We are grateful for all the contributions made by the investigators and patients in this study – together we accomplished this important milestone."

About Non-Squamous Non-Small Cell Lung Cancer (NSCLC)

Lung cancer is the leading cause of cancer death worldwide, and the second most commonly diagnosed tumor type. Non-small cell lung cancer (NSCLC) accounts for about 80% to 85% of all lung cancer, in which about 70% of NSCLC patients present with locally advanced or metastatic disease that is not suitable for surgical resection at diagnosis. In China, nsqNSCLC accounts for 70% of NSCLC, in which about 40% to 50% of nsqNSCLC patients have an EGFR mutation. The standard first-line treatment for patients with advanced EGFR-mutated NSCLC is a third generation EGFR TKI, or first or second generation EGFR TKI. For patients who have progressed following EGFR-TKI treatment, platinum-based chemotherapy is still the standard therapy with limited benefit, representing a large unmet medical need.

About the ORIENT-31 Study

ORIENT-31 is a randomized, double-blind, multicenter Phase 3 clinical study evaluating sintilimab, with or without BYVASDA (bevacizumab biosimilar injection), combined with chemotherapy (pemetrexed and cisplatin) in patients with EGFR-mutated locally advanced or metastatic non-squamous NSCLC who have progressed following EGFR TKI treatment (ClinicalTrials.gov, NCT003802240). The primary endpoint is PFS as assessed by BIRRC based on RECIST v1.1. The secondary endpoints include overall survival (OS), PFS as assessed by investigators, objective response rate (ORR) and safety.

Eligible patients included: patients with disease progression following first or second generation EGFR TKI and confirmed as T790M negative, or T790M positive but further progressed on third generation EGFR-TKI treatment, or patients with disease progression following third generation EGFR-TKI as first line treatment.

Patients were randomized in a 1:1:1 ratio to receive sintilimab plus BYVASDA (bevacizumab biosimilar injection) combined with pemetrexed and cisplatin, sintilimab plus placebo 2 combined with pemetrexed and cisplatin, or placebo 1 plus placebo 2 combined with pemetrexed and cisplatin. After 4 cycles of combination treatment, patients will receive maintenance treatment of sintilimab plus BYVASDA and pemetrexed, sintilimab plus placebo 2 and pemetrexed, placebo 1 plus placebo 2 and pemetrexed, until radiographic disease progression, unacceptable toxicity or any other conditions that required treatment discontinuation. Target accrual is 480 patients.

About Sintilimab

Sintilimab, marketed as TYVYT (sintilimab injection) in China, is an innovative PD-1 inhibitor with global quality standards jointly developed by Innovent and Eli Lilly and Company. Sintilimab is an immunoglobulin G4 monoclonal antibody, which binds to PD-1 molecules on the surface of T-cells, blocks the PD-1 / PD-Ligand 1 (PD-L1) pathway, and reactivates T-cells to kill cancer cells. Innovent is currently conducting more than 20 clinical studies of sintilimab worldwide, to evaluate its safety and efficacy in a wide variety of cancer indications, including more than 10 registrational or pivotal clinical trials.

In China, sintilimab has been approved for four indications, including:

The treatment of relapsed or refractory classic Hodgkin’s lymphoma after two lines or later of systemic chemotherapy
In combination with pemetrexed and platinum chemotherapy, for the first-line treatment of nonsquamous non-small cell lung cancer
In combination with gemcitabine and platinum chemotherapy, for the first-line treatment of squamous non-small cell lung cancer
In combination with BYVASDA (bevacizumab biosimilar injection) for the first-line treatment of hepatocellular carcinoma
Additionally, Innovent currently has one regulatory submission under review in China for sintilimab, for the first line treatment of esophageal squamous cell carcinoma.

Additionally, four clinical studies of sintilimab have met their primary endpoints:

Phase 3 study in combination with oxaliplatin and capecitabine for the first-line treatment of unresectable, locally advanced, recurrent or metastatic gastric or gastroesophageal junction adenocarcinoma.
Phase 2 study as second-line treatment of esophageal squamous cell carcinoma
Phase 3 study as second-line treatment for squamous NSCLC with disease progression following platinum-based chemotherapy
Phase 3 study in combination with BYVASDA (bevacizumab biosimilar injection) and chemotherapy (pemetrexed and cisplatin) for EGFR-mutated nonsquamous NSCLC following EGFR-TKI treatment.
In May 2021, the U.S. FDA accepted for review the Biologics License Application (BLA) for sintilimab in combination with pemetrexed and platinum chemotherapy for the first-line treatment of nonsquamous non-small cell lung cancer.

Sintilimab was included in China’s National Reimbursement Drug List (NRDL) in 2019 as the first PD-1 inhibitor and the only PD-1 included in the list in that year.

About BYVASDA (bevacizumab biosimilar injection)

BYVASDA, also known as IBI305, is a bevacizumab biosimilar and a recombinant humanized anti-VEGF monoclonal antibody drug. Vascular endothelial growth factor (VEGF) is an important factor in angiogenesis that is highly expressed by the endothelial cells in most human tumors. An anti-VEGF antibody binds VEGF-A selectively with high affinity and blocks its binding to VEGF-2 receptors on the surface of vascular endothelial cells, thereby inhibiting signaling pathways such as PI3K-Akt/PKB and Ras-Raf-MEK-ERK. BYVASDA produces anti-tumor effects by inhibiting the growth, proliferation and migration of vascular endothelial cells, blocking angiogenesis, reducing vascular permeability, blocking blood supply to tumor tissues, inhibiting the proliferation and metastasis of tumor cells and inducing apoptosis in tumor cells. Since its launch, bevacizumab has been approved for the treatment of patients with multiple malignant tumors globally, including non-small cell lung cancer, metastatic colorectal cancer, glioblastoma, renal cell carcinoma, cervical cancer, and epithelial ovarian, fallopian tube, or primary peritoneal cancer. The efficacy and safety of bevacizumab in these tumor types have been well recognized worldwide.

In China, BYVASDA (bevacizumab biosimilar injection) is approved for indications including advanced non-small cell lung cancer, metastatic colorectal cancer, adult recurrent glioblastoma, and advanced or unresectable hepatocellular carcinoma.

Tyligand Bioscience Receives IND Clearance from U.S. FDA for TSN084, a Multi-kinase Inhibitor to Address Tumor Resistance to Targeted Therapies

On October 16, 2021 Tyligand Bioscience, a clinical-stage biotechnology company developing innovative small-molecule therapeutics against drug resistant cancers, reported that the U.S. Food and Drug Administration (FDA) has cleared an Investigational New Drug (IND) application for its novel drug TSN084 for treating solid tumors (Press release, Tyligand Bioscience, OCT 16, 2021, View Source [SID1234644990]). TSN084 is a first-in-class multi-kinase inhibitor targeting CDK8/19 and several other kinases implicated in tumorigenesis and immune evasions. The clinical study is about to start at M.D Anderson Cancer Center in the US soon.

Dr. Tony Zhang, cofounder and CEO of Tyligand Bioscience, commented, "TSN084 is the front runner of the Tyligand pipeline of molecules designed to treat tumors that become resistant to targeted therapies. We hope the potent activities demonstrated by TSN084 against a unique combination of kinase targets responsible for several major cancer hallmarks in preclinical studies can be translated into clinical outcomes for patients suffering NSCLC and TNBC. FDA’s clearance has moved us one step closer towards achieving that goal！"

Pepper Bio Emerges from Stealth with ‘Waze for Drug Discovery’ Technology

On October 15, 2021 Pepper Bio, the world’s first transomics drug discovery company, reported the company emerges from stealth to leverage its proprietary transomics — including phosphoproteomics — data translation technology to discover new drugs, rediscover new uses for existing therapeutics, and rescue drugs that may be on a course toward failing (Press release, Pepper Bio, OCT 15, 2021, View Source [SID1234638709]).

Drug discovery is often a bad bet for pharma. Pepper Bio significantly reduces that risk.
Currently, the successful development of a new therapy is estimated to cost around $2.6 billion on average and last over a decade through a variety of failed and successful trials. Because of the high cost and risks involved, many diseases will go untreated because of their low expected return on investment in drugs that may work. With hundreds of thousands of therapeutics candidates being evaluated each year, 86 percent of clinical trials of drug candidates fail to earn FDA approval, according to a new study from the MIT Sloan School of Management. More than 30 percent of drugs entering Phase II clinical trials fail to progress, and 58 percent of drugs fail in Phase III. These end-stage studies commonly cost upward of hundreds of millions of dollars for manufacturing, clinical trial design, implementation, and data analysis.

"From my experience as a drug development strategist, many therapeutic programs were killed simply because they would have cost too much with an inadequate return on investment," said Jon Hu, co-founder and CEO, Pepper Bio. "These are very difficult decisions because they are made with the understanding that many people who may benefit from these potential new drugs would never have that opportunity. We founded Pepper Bio in order to significantly improve the volume, quality, and accuracy of the data analysis used to evaluate opportunities for novel new therapeutics. We empower our drug discovery partners with a much higher level of informed confidence. Ultimately, our work will result in many more drug development initiatives going forward to help people around the world struggling with diseases that are left untreated today."

A first in drug discovery, Pepper Bio and their partners make significantly more informed strategic decisions by relying on more accurately analyzed data. This allows them to develop therapeutics that treat diseases at their root cause, have less toxicity and higher response rates with patients exhibiting fewer symptoms. Already, Pepper Bio has demonstrated proof of concept of the company’s proprietary platform across three therapeutic areas: Neurodegenerative, Oncology, and Inflammatory.

Pepper Bio’s proprietary capability to translate multiple levels of complex transomic data unlocks a new level of sophistication in drug discovery, much like Waze leverages multiple layers of data to direct travelers on the optimal and safe road to their destination. Pepper Bio identifies how and why novel drug candidates may or may not be effective in specific patient populations and diseases, directing drug discovery initiatives toward the most promising disease targets and patients who will be helped most with reduced side effects.

The success of Pepper Bio is rooted in the company’s proprietary capacity to access and analyze transomic data leveraging three pillars of the field: Global (1), comprehensive data from the entire biological system are analyzed to determine functional (2) characteristics of intercellular biologic activity. Multiple omic layers, including phosphoproteomics, the layer at the top of the biotech stack, are analyzed. By analyzing all layers combined, Pepper Bio empowers drug developers to identify and reach accurate, much more informed causal (3) inferences.

"Pepper Bio is working to ensure that the right therapeutics and combinations of drugs are developed in a precise, effective, efficient, and safe manner. Our proprietary capacity to translate complex transomic data into meaningful, evidence-based guidance for drug discovery programs significantly improves the likelihood of success for clinical trials. This promises to conserve many millions of dollars that may otherwise be funneled into traditional methods of research and development," said Samantha Dale Strasser, Ph.D., Co-Founder and Chief Scientific Officer, Pepper Bio.

The industry moving towards transomics is inevitable and Pepper Bio is leading the way." said Omri Amirav Drory, General Partner at NFX, an investor in Pepper Bio. NFX was an early backer of biotech companies such as Mammoth Biosciences and c2i genomics.

CEO Jon Hu is experienced in pharmaceutical research and development (Shire Pharmaceuticals), corporate strategic consulting (Bain & Company), and venture capital (Guild Capital). Hu earned his Bachelor’s degrees in biomedical engineering and economics, and earned his MBA from Harvard Business School. CSO Samantha Dale Strasser, Ph.D., developed the foundation of Peppe Bio’s technology during her time as a National Science Foundation Graduate Research Fellow at the Massachusetts Institute of Technology, where she earned her Doctorate in Electrical Engineering and Computer Science. She earned her Master’s Degree in M.Phil in Physics at the University of Cambridge as a Churchill Scholar and her Bachelor’s degrees in Biomedical Engineering and Applied Mathematics from Northwestern University.

Mr. Hu and Dr. Strasser are joined by Christopher Nicholson, Ph.D., Head of Biology, and Caitlin Brown, Ph.D., Head of Business Development. Dr. Nicholson earned his doctorate from Newcastle University and was a Senior Research Fellow at Harvard Medical School and MGH. Dr. Brown earned her doctorate from Brown University.

Pepper Bio announced its scientific and strategic advisory board members today: Douglas Lauffenberger, Ph.D., Professor, MIT; Founder, Biological Engineering, MIT.; Dean Felsher, MD, Ph.D., Professor, Oncology, Stanford; Director, Translational Research, Stanford. Imran Nasrullah, JD, VP & Head, Open Innovation Center, North America – East, Bayer; Former Director, Strategic Partnering & Business Development & Licensing, Boehringer-Ingelheim. Tom Rush, Ph.D., Chief R&D Officer, Variant Bio; Former US Lead, Functional Genomics, GlaxoSmithKline. Jerome Windsor, PharmD, SVP, Corporate Development & Product Strategy, GNS Healthcare; Former VP, Strategy & Business Development, Median Technologies. Peter Hornbeck, Ph.D., Director, Cell Signaling Technology; Founder, PhosphoSitePlus.

Hervolution receives 2.5M EUR in funding through the European Innovation Council Accelerator

On October 15, 2021 Hervolution Therapeutics reported that Hervolution is one of just 65 European companies to receive funding through the European Innovation Council Accelerator of 2.5M EUR (Press release, Hervolution Therapeutics, OCT 15, 2021, View Source [SID1234637208]).