On May 9, 2020 Avalon GloboCare Corp. (NASDAQ: AVCO), a clinical-stage global developer of cell-based technologies and therapeutics, reported that it has achieved significant milestones, advancing its next generation immune cell therapy using FLASH-CAR technology co-developed with the Company’s strategic partner Arbele Limited (Press release, Avalon, MAY 9, 2020, View Source [SID1234609546]). The adaptable FLASH-CAR platform can be used to create personalized cell therapy from a patient’s own cells, as well as off-the-shelf cell therapy from a universal donor.
Currently available Chimeric Antigen Receptor T (CAR-T) cellular immunotherapy involves a patient’s own T-cells—a type of white blood cell that protects against infections and other diseases including cancer—that are turned into personalized cancer fighting cells. The T-cells are removed from the patient, reprogrammed in the lab using a viral vector to target cancer cells, and infused back into the patient as a cancer immunotherapy.

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In contrast to these existing therapies, Avalon’s FLASH-CAR uses next generation CAR technology to modify patients’ T-cells and natural killer (NK) cells using a ribonucleic acid (RNA)-based platform rather than a viral vector. Similar to T-cells, NK cells are a type of white blood cell, also able to attack cancer cells, but utilize different mechanisms. By using RNA molecules rather than a viral vector, Avalon’s RNA-based CAR technology is designed to rapidly create personalized CAR therapies in 1 to 2 days compared to the 10- to 14-day bio-manufacturing time necessary to generate currently available CAR-T cellular immunotherapy. Avalon’s FLASH-CAR technology is also designed to reprogram the immune cells to hone in on multiple crucial cancer cell targets, called tumor antigens, to potentially achieve superior therapeutic effect. Avoiding the use of viral vectors and complicated bio-processing procedures significantly reduces manufacturing costs, resulting in a more affordable and potentially breakthrough therapy for cancer patients. The FLASH-CAR technology can also be used to generate "off-the-shelf", universal cell therapy that has the potential to reach even more patients.

Avalon’s first FLASH-CAR platform candidate, AVA-011, targets both CD19 and CD22 tumor antigens on cancer cells. Pre-clinical research on AVA-011, including tumor cytotoxicity studies, has been successfully completed and Avalon is immediately entering the process development stage to generate clinical-grade CAR-T and CAR-NK cells for use in human clinical trials. Avalon and Arbele have jointly filed for USPTO provisional and PCT patents for this RNA-based CAR platform cellular therapy and for other applications.

Avalon expects to begin a first-in-human clinical trial with AVA-011 for the treatment of relapsed or refractory B-cell lymphoblastic leukemia (B-ALL) and non-Hodgkin lymphoma in the first quarter of 2021. The goal is to use AVA-011 as a bridge to bone marrow stem cell transplant therapy, currently the only curative approach for patients with these blood cancers.

"Avalon GloboCare is committed to decreasing the time it takes to deliver cellular immunotherapies to cancer patients, as well as lowering the cost of manufacturing by building on our unique RNA-based CAR platform that does not require using a viral vector," stated David Jin, M.D., Ph.D., President and Chief Executive Officer of Avalon GloboCare. "We are accelerating our innovative discovery and development plan, as well as delivering precise clinical execution and leadership in cellular immunotherapy. Our pre-clinical studies are encouraging and we are excited for AVA-011 to enter the clinical development stage, including multi-center clinical trials following completion of process development to generate the cell therapy," said Dr. Jin.

"Through this strategic partnership with Avalon GloboCare, we envision an accelerated scientific and clinical development of the RNA-based FLASH-CAR technology platform with great potential to generate "off-the-shelf" immune effector cell therapies to treat both hematologic and solid malignancies," said John Luk, Ph.D., EMBA, President and Chief Executive Officer of Arbele Limited.

On May 9, 2020 Cinda Biopharmaceutical (Hong Kong Stock Exchange: 01801), an innovative drug dedicated to the development, production and sale of major diseases such as cancer, autoimmunity, metabolic diseases, etc. The biopharmaceutical company, and Eli Lilly (NYSE: LLY) reported : A randomized, innovative, and innovative PD-1 inhibitor Daboshu (Sindilimumab Injection) jointly developed by the two parties (Press release, Innovent Biologics, MAY 9, 2020, View Source [SID1234557375]). Double-blind, phase III controlled clinical study (ORIENT-12)-Daboshu (sindilimumab injection, hereinafter referred to as sinidiumab) combined with Gemcitabine (gemcitabine for injection, hereinafter referred to as gemcitabine) Platinum-based chemotherapy is used in the first-line treatment of advanced or metastatic squamous non-small cell lung cancer (NSCLC) to reach the primary study endpoint. This is the world ’s first randomized, double-blind, phase III clinical study evaluating PD-1 antibody combined with Gemcitabine (gemcitabine) and platinum for first-line treatment of squamous NSCLC.

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Studies have shown that Sindilimum combined with gemcitabine and platinum compared with placebo combined with gemcitabine and platinum, significantly prolonged progression-free survival (PFS), reached the preset study endpoint, PFS significantly benefited, safety characteristics and previous reports The research results of xindilimumab were consistent and there was no new safety signal. Detailed research results will be announced in subsequent academic conferences.

Cinda and Eli Lilly plan to communicate with the Drug Evaluation Center (CDE) of the State Drug Administration on the submission of a new indication for the application of cindilimumab combined with gemcitabine and platinum for first-line treatment of squamous NSCLC.

Professor Zhou Caicun, director of the Department of Oncology, Shanghai Pulmonary Hospital, said: "Lung cancer accounts for the first cause (25.2%) of all cancer deaths, of which NSCLC accounts for approximately 80% to 85%. About 35% of NSCLC are squamous NSCLC. Over the past two decades, the development of drugs for the treatment of NSCLC has mainly focused on non-squamous NSCLC. Due to the lack of driver genes and special tumor biological characteristics, drug development has been slow. The emergence of anti-PD-1 antibodies is This type of patient brings a new treatment. We see that the study of Sindilimum reached the preset primary study end point. The ORIENT-12 study compared with the KEYNOTE-407 study of pabolizumab Using different combination chemotherapy regimens, it is the first randomized controlled study in the world to confirm that PD-1 antibody combined with gemcitabine and platinum can significantly improve the benefit of progression-free survival in patients with first-line squamous NSCLC. "

Dr. Hui Zhou, Vice President of the Medical Science and Strategic Oncology Department of Cinda Biopharmaceutical Group, said: "Currently Cindylimumab is the only anti-PD-1 monoclonal antibody drug listed in the National Medical Insurance List. It was awarded the National Drug Administration in 2018 Approved by the Administration for the treatment of relapsed or refractory classic Hodgkin’s lymphoma after at least second-line chemotherapy. We are currently conducting a number of phase III randomized controlled studies on Sindrinimab. ORIENT-12 The results of the study are encouraging, and we foresee the potential of Sindilimumab to benefit more lung cancer patients. This is also the main study of Cinda Biological following ORIENT-11 (first-line non-squamous NSCLC randomized, double-blind, phase III study, NCT03607539) After the end point, the second successful randomized controlled study of lung cancer. "

Dr. Li Wang, senior vice president of Eli Lilly China and head of the Center for Drug Development and Medical Affairs, said, "Not long ago, the Drug Evaluation Center (CDE) of the State Drug Administration accepted Cindilimum for non-squamous non-small The application of new indications for first-line treatment of cell lung cancer (nsqNSCLC). And the exciting research results of ORIENT-12 have reflected the potential of Sindilimumab in the treatment of squamous non-small cell lung cancer. Here we think Thanks to all the patients and their families, researchers and clinical trial centers, and Cinda colleagues who participated in the study. We look forward to bringing this new treatment to lung cancer patients in China as soon as possible. "

About ORIENT-12 research

The ORIENT-12 study is a randomized evaluation of the efficacy and safety of Daboshu (sintilimab) or placebo in combination with Gemcitabine (gemcitabine) and platinum for first-line treatment of advanced or metastatic squamous NSCLC , Double-blind, Phase III controlled clinical study (ClinicalTrials.gov, NCT03629925). The primary study endpoint was progression-free survival (PFS) assessed by the Independent Imaging Review Committee (IRRC) according to the RECIST v1.1 standard. Secondary study endpoints include overall survival (OS) and safety.

A total of 357 subjects were enrolled in this study. They were randomized 1: 1 and received Daboshu (Sintilimab injection) 200 mg or placebo in combination with Gemcitabine (gemcitabine for injection) and platinum Treatment, given once every 3 weeks, after completing 4 or 6 cycles of combination therapy, enter Daboshu (sindilimumab injection) or placebo for maintenance therapy until disease progression, toxicity intolerance or other Circumstances where treatment needs to be terminated. After the disease progresses in the control group, it can be conditionally crossed to monotherapy of daboshu (sintilimab injection).

About squamous non-small cell lung cancer (sqNSCLC)

Lung cancer is the first malignant tumor in China that ranks first in both morbidity and mortality. NSCLC accounts for about 80% to 85% of all lung cancers, and about 70% of NSCLC patients are diagnosed as locally advanced or metastatic tumors that are not suitable for radical surgery. At the same time, a considerable proportion of early-stage NSCLC patients undergoing surgery will have recurrence or distant metastasis, and then die due to disease progression. About 35% of Chinese patients with NSCLC are squamous NSCLC. Squamous NSCLC lacks driver genes, and the effectiveness of first-line chemotherapy is about 30%. At present, only paclizumab combined with carboplatin and paclitaxel has been approved by the FDA and the National Drug Administration (NMPA) for this population. Treatment is still limited, and there are huge unmet medical needs.

About Daboshu (Sintilimab Injection)

Daboshu (Sintilimab Injection) is an innovative biopharmaceutical of international quality jointly developed by Cinda Biopharma and Eli Lilly in China. The first indication for its approval is relapsed / refractory classic Hodgkin’s lymphoma, which was included in the 2019 edition of the Chinese Society of Clinical Oncology (CSCO) lymphoma diagnosis and treatment guidelines. In April 2020, the National Drug Administration (NMPA) formally accepted the application for indications for the first-line treatment of non-squamous non-small cell lung cancer (nsqNSCLC) with dabershu (sintilimab injection). In the medical insurance country talks in 2019, Dabex (Sintilimab Injection) is the only PD-1 inhibitor that enters the National Health Insurance.

Dabshu (Sindilimumab Injection) is a human immunoglobulin G4 (IgG4) monoclonal antibody that specifically binds to PD-1 molecules on the surface of T cells, thereby blocking tumor immune tolerance The PD-1 / Programmed Death Receptor Ligand 1 (Programmed Death-Ligand 1, PD-L1) pathway reactivates the anti-tumor activity of lymphocytes to achieve the purpose of treating tumors. There are currently more than twenty clinical studies (of which more than 10 are registered clinical trials) are underway to explore the anti-tumor effect of sundilimumab on other solid tumors. Cinda Biotech is also conducting clinical research work on Cindylimumab injections worldwide.

On May 8, 2020 Zydus Cadila, a global innovation driven healthcare company, reported that it is launching Enzalutamide, a highly effective drug for the treatment of Prostate Cancer, under the brand name ‘Obnyx’ in India (Press release, Zydus Cadila, MAY 8, 2020, View Source [SID1234558211]). In a step that can significantly reduce treatment cost by almost 70%, the drug is priced at Rs 5995 (weekly therapy) reducing the monthly treatment cost to less than Rs. 27000. The current MRP of Enzalutamide drug ranges from Rs. 70000 to Rs 80000 for a monthly therapy and can be a huge financial burden for the elderly patients as they need to continue the therapy for a long period of time. This price reduction will benefit many prostate cancer patients to adhere to the treatment.

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One of the important aspects of prostate cancer treatment is reducing the effect of androgens (a male reproductive hormone) on prostate gland. Many patients require Androgen Receptor Targeted Therapies like Enzalutamide which works by blocking the effects of androgen to stop the growth and spread of prostate cancer cells. More importantly, it is a preferred option in patients with significant liver, heart and kidney diseases which is very common in the elderly men. Enzalutamide has an advantage of being taken through oral route. Zydus’ Obnyx scores over other formulations in the market as it is a soft gel capsule filled with liquid, similar to the innovator drug. This has been specially developed through in-house efforts. The other formulations available in the market are hard gelatin capsules.

Prostate cancer is one of the leading cancer in males in India and the risk increases with age. About 1 out of 9 men have risk of developing prostate cancer in lifetime. The incidence is nearly 60% in men over the age of 65 years. Other risk factors such as obesity, family history and improper diet have been identified as the main contributing factors towards an increased incidence of prostate cancer.

On May 8, 2020 Bonnie J Addario Lung Cancer Foundation reported that the U.S. Food and Drug Administration approved Retevmo (selpercatinib) capsules to treat three types of tumors – non-small cell lung cancer, medullary thyroid cancer and other types of thyroid cancers – in patients whose tumors have an alteration (mutation or fusion) in a specific gene (RET or "rearranged during transfection") (Press release, Bonnie J Addario Lung Cancer Foundation, MAY 8, 2020, View Source [SID1234557485]). Retevmo is the first therapy approved specifically for cancer patients with the RET gene alterations.

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"Innovations in gene-specific therapies continue to advance the practice of medicine at a rapid pace and offer options to patients who previously had few," said Richard Pazdur, M.D., director of the FDA’s Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA’s Center for Drug Evaluation and Research. "The FDA is committed to reviewing treatments like Retevmo that are targeted to specific subsets of patients with cancer."

Specifically, the cancers that Retevmo is approved to treat include:

Non-small cell lung cancer (NSCLC) that has spread in adults,
Advanced medullary thyroid cancer (MTC) or MTC that has spread, in patients 12 and older who require systemic therapy (a treatment option that spreads across the entire body, is not targeted), and
Advanced RET fusion-positive thyroid cancer in those age 12 and older that requires systemic therapy that has stopped responding to radioactive iodine therapy or is not appropriate for radioactive iodine therapy.
Retevmo is a kinase inhibitor, meaning it blocks a type of enzyme (kinase) and helps prevent the cancer cells from growing. Before beginning treatment, the identification of a RET gene alteration must be determined using laboratory testing.

The FDA approved Retevmo on the results of a clinical trial involving patients with each of the three types of tumors. During the clinical trial, patients received 160 mg Retevmo orally twice daily until disease progression or unacceptable toxicity. The major efficacy outcome measures were overall response rate (ORR), which reflects the percentage of patients that had a certain amount of tumor shrinkage, and duration of response (DOR).

Efficacy for NSCLC was evaluated in 105 adult patients with RET fusion-positive NSCLC who were previously treated with platinum chemotherapy. The ORR for the 105 patients was 64%. For 81% of patients who had a response to the treatment, their response lasted at least six months. Efficacy was also evaluated in 39 patients with RET fusion-positive NSCLC who had never undergone treatment. The ORR for these patients was 84%. For 58% of patients who had a response to the treatment, their response lasted at least six months.

Efficacy for MTC in adults and pediatric patients was evaluated in those 12 years of age and older with RET-mutant MTC. The study enrolled 143 patients with advanced or metastatic RET-mutant MTC who had been previously treated with cabozantinib, vandetanib or both (types of chemotherapy), and patients with advanced or metastatic RET-mutant MTC who had not received prior treatment with cabozantinib or vandetanib. The ORR for the 55 previously treated patients was 69%. For 76% of patients who had a response to the treatment, their response lasted at least six months. Efficacy was also evaluated in 88 patients who had not been previously treated with an approved therapy for MTC. The ORR for these patients was 73%. For 61% of patients who had a response to the treatment, their response lasted at least six months.

Efficacy for RET fusion-positive thyroid cancer was evaluated in adults and pediatric patients 12 years of age and older. The study enrolled 19 patients with RET fusion-positive thyroid cancer who were radioactive iodine-refractory (RAI, if an appropriate treatment option) and had received another prior systemic treatment, and eight patients with RET fusion-positive thyroid cancer who were RAI-refractory and had not received any additional therapy. The ORR for the 19 previously treated patients was 79%. For 87% of patients who had a response to the treatment, their response lasted at least six months. Efficacy was also evaluated in eight patients who had not received therapy other than RAI. The ORR for these patients was 100%. For 75% of patients who had a response to the treatment, their response lasted at least six months.

The most common side effects with Retevmo were increased aspartate aminotransferase (AST) and alanine aminotransferase (ALT) enzymes in the liver, increased blood sugar, decreased white blood cell count, decreased albumin in the blood, decreased calcium in the blood, dry mouth, diarrhea, increased creatinine (which can measure kidney function), increased alkaline phosphatase (an enzyme found in the liver and bones), hypertension, fatigue, swelling in the body or limbs, low blood platelet count, increased cholesterol, rash, constipation and decreased sodium in the blood.

Retevmo can cause serious side effects including hepatotoxicity (liver damage or injury), elevated blood pressure, QT prolongation (the heart muscle takes longer than normal to recharge between beats), bleeding and allergic reactions. If a patient experiences hepatotoxicity, Retevmo should be withheld, dose reduced or permanently discontinued. Patients undergoing surgery should tell their doctor as drugs similar to Retevmo have caused problems with wound healing.

Retevmo may cause harm to a developing fetus or a newborn baby. Health care professionals should advise pregnant women of this risk and should advise both females of reproductive potential and males patients with female partners of reproductive potential to use effective contraception during treatment with Retevmo and for one week after the last dose. Additionally, women should not breastfeed while on Retevmo.

Retevmo was approved under the Accelerated Approval pathway, which provides for the approval of drugs that treat serious or life-threatening diseases and generally provide a meaningful advantage over existing treatments. The FDA also granted this application Priority Review and Breakthrough Therapy designation, which expedites the development and review of drugs that are intended to treat a serious condition, when preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapies. Additionally, Retevmo received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.

The FDA granted approval of Retevmo to Loxo Oncology, Inc., a subsidiary of Eli Lilly and Company.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

On May 8, 2020 Ayala Pharmaceuticals reported that it has two clinical-stage cancer drugs licensed from Bristol Myers Squibb (Press release, Ayala Pharmaceuticals, MAY 8, 2020, View Source [SID1234557442]). Now it has $55 million to take those drugs further than the pharmaceutical giant did.

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On Thursday evening, Ayala priced its IPO, which consisted of 3.7 million shares sold for $15 each. That price was the midpoint of the targeted $14 to $16 per share range, but the Rehovot, Israel-based company was able to increase the number of shares in the offering by 10 percent. Ayala is expected to begin trading on the Nasdaq Friday under the stock symbol "AYLA."

Ayala’s lead candidate, AL101, is an injectable small molecule that blocks gamma secretase, an enzyme that activates the Notch signaling pathway. This pathway plays a role in both solid tumors and blood cancers. Bristol (NYSE: BMY) had tested the drug in three Phase 1 studies—all of them failures.

Ayala is trying for a better outcome. In its prospectus, the company says patients in the Bristol studies weren’t selected according to whether their cancers were characterized by Notch activation. Ayala uses DNA sequencing technology to identify patients whose cancers are most likely to respond to AL101. The company is currently testing the drug in an open-label Phase 2 study enrolling patients with adenoid cystic carcinoma, a rare form of cancer affecting secretary glands, such as the salivary glands.

Of the estimated 3,400 patients who have adenoid cystic carcinoma, Ayala says about 1,700 have disease that is recurrent or metastatic. The company calculates that 18 to 20 percent of these patients have cancers with Notch-activating mutations. There are no FDA-approved drugs for this cancer.

As of April 28, Ayala has some early data safety and efficacy data from its Phase 2 test of AL101, according to the prospectus. Additional data will be presented at medical conferences in the second half of this year. Ayala also plans to test AL101 in two other cancers characterized by Notch pathway activation: triple negative breast cancer and acute lymphoblastic leukemia.

Ayala’s second compound, an oral drug called AL102, is also a gamma secretase inhibitor. The company is developing the former Bristol compound as a treatment for desmoid tumors, which occur in connective tissue. There are currently no FDA-approved therapies for desmoid tumors, though SpringWorks Therapeutics (NASDAQ: SWTX) is in the hunt testing a drug licensed from Pfizer (NYSE: PFE). The SpringWorks compound is in Phase 3 testing. Ayala plans to start a Phase 2 trial for its desmoid tumor drug candidate in the second half of this year.

AL102 is also being developed as a potential treatment for multiple myeloma under a partnership with Novartis (NYSE: NVS). The plan is to evaluate the drug in combination with Novartis’s B-cell maturation antigen therapies. The agreement gives the Swiss pharma giant the option to license the Ayala drug. A Phase 1 study has started but patients have not yet been dosed, according to the prospectus. The agreement calls for Novartis to pay up to $4.3 million of Ayala’s research and development expenses.

Ayala plans to use $13 million to $14 million to advance AL101 through the adenoid cystic carcinoma Phase 2 study, the company says in its IPO documents. Another $11 million to $12 million is earmarked for the planned mid-stage study in triple negative breast cancer; $6 million to $7 million for the acute lymphoblastic leukemia test. AL102 will require $7 million to $8 million for the Phase 2 study in desmoid tumors.

Ayala formed in 2017, the same year it licensed AL101 and AL102 from Bristol. The biotech says it has raised $46.3 million since its launch. The company’s largest shareholder is Israel Biotech Fund, which holds a 25.5 percent post-IPO stake, according to the prospectus. Novartis owns 5.2 percent of the biotech; Bristol 4.6 percent.