On June 3, 2021 Paige, the global leader in AI-based diagnostic software in pathology, reported that leading pathologist and Paige co-founder David Klimstra, M.D. has joined as Chief Medical Officer effective August 2021 (Press release, Paige AI, JUN 3, 2021, View Source [SID1234583477]). Dr. Klimstra is an internationally recognized leader in cancer pathology whose career spans more than three decades. In this new role, Dr. Klimstra will lead the clinical implementation and evidence generation for Paige’s technology and will shape product strategy for the most compelling use cases, helping pathologists realize the benefits of the enhanced clinical workflows enabled by Paige’s technology.

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"We are thrilled to welcome Dr. Klimstra into his new role as we launch digital pathology products into clinics worldwide while ramping up development programs for new tissue types," said Leo Grady, Ph.D., Chief Executive Officer of Paige. "As a leading pioneer in pathology and digital pathology, Dr. Klimstra has a deep understanding of how AI-based technology can help pathologists overcome the challenges they face in their daily practice and has the first-hand experience to guide hospital groups and labs who are going digital."

Dr. Klimstra is currently Chair of the Department of Pathology at Memorial Sloan Kettering Cancer Center (MSK) and holds the James Ewing Alumni Chair of Pathology. As Chair, Dr. Klimstra has led the evaluation and implementation of digital pathology workflows at MSK and built an academic computational pathology program. During his 10 years leading the Department, he doubled the number of pathology faculty and broadened the department’s scope by recruiting a range of experts, including in bioinformatics, engineering, spectrometry and mathematics. His leadership has emphasized the introduction of new technology into the practice of pathology, with digital and computational pathology as key examples.

"As a co-founder of Paige and through my clinical practice, I have seen that digital pathology is the future of our discipline, and the application of AI to digital pathology is the pathway to drive adoption," said Dr. Klimstra. "I am extremely impressed with the progress Paige has made in a short time and am eager to formally join this endeavor and work with the team to deliver on the promise of computational pathology for widespread clinical use."

Additionally, Dr. Klimstra has also authored more than 450 peer-reviewed publications related to his research on the pathology of pancreatic, hepatic, and gastrointestinal tumors. He has served as an editor of the World Health Organization’s standard classification series for tumors of the gastrointestinal tract and endocrine organs and he has authored four books and numerous book chapters. He is widely sought for his diagnostic expertise and has lectured extensively around the world.

"Dr. Klimstra’s arrival comes at a pivotal moment as we define the trajectory for clinical implementation of our products," said Thomas J. Fuchs, Dr.Sc., co-founder and Chief Scientist of Paige. "He knows the value of novel diagnostic technologies in pathology, having built one of the most technologically advanced pathology departments through the implementation of digital pathology, next-generation sequencing and many other sophisticated diagnostic modalities. I am tremendously excited about working closely with David to propel Paige’s vision and scientific leadership forward to serve the pathology community and its patients."

On June 3, 2021 Innovent Biologics, Inc. (Innovent) (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of cancer, metabolic, autoimmune and other major diseases, and Eli Lilly and Company (NYSE: LLY) reported that the National Medical Products Administration (NMPA) of China has approved the supplemental New Drug Application (sNDA) for TYVYT (sintilimab injection) in combination with gemcitabine and platinum chemotherapy as first-line therapy for people with unresectable locally advanced or metastatic squamous non-small cell lung cancer (sqNSCLC) (Press release, Innovent Biologics, JUN 3, 2021, View Source [SID1234583493]).

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This is the third NMPA-approved indication of TYVYT (sintilimab injection), following the approval in December 2018 for the treatment of relapsed or refractory classical Hodgkin’s lymphoma, and the approval in February 2021 for the first-line treatment of nonsquamous non-small cell lung cancer (nsqNSCLC). This is also the first regulatory approval of a PD-1/PD-L1 immunotherapy in combination with gemcitabine and platinum chemotherapy for the first-line treatment for people with sqNSCLC.

This new approval was based on a randomized, double-blind, Phase 3 clinical trial (ORIENT-12) which evaluated TYVYT (sintilimab injection) or placebo in combination with GEMZAR (gemcitabine) and platinum chemotherapy as first-line therapy for people with unresectable locally advanced or metastatic sqNSCLC.

Professor Caicun Zhou, head of the Oncology Department at Shanghai Pulmonary Hospital, stated: "Lung cancer is the leading cause (nearly 25%) of all cancer deaths, of which non-small cell lung cancer accounts for about 80 to 85 percent. Approximately 70 percent of patients with non-small cell lung cancer have unresectable tumors at the time of diagnosis, and 30 to 60 percent of patients with Stage I-III non-small cell lung cancer who undergo radical surgery subsequently have recurrence or distant metastasis. Over the past two decades, drug development for non-small cell lung cancer has been mainly focused on nonsquamous non-small cell lung cancer, while drug development for squamous non-small cell lung cancer has been relatively slow due to its unique epidemiology, histopathology and molecular biology. The ORIENT-12 study showed that, in the first-line treatment of patients with squamous non-small cell lung cancer, TYVYT (sintilimab injection) in combination with gemcitabine and platinum chemotherapy demonstrated a statistically significant improvement in progression-free survival compared to placebo and gemcitabine and platinum chemotherapy. Meanwhile, although the median overall survival data was not yet mature, the TYVYT (sintilimab injection) combination arm showed a potential overall survival benefit over chemotherapy alone. The approval of TYVYT (sintilimab injection) provides a new clinical approach in China for the first-line treatment of advanced or metastatic squamous non-small cell lung cancer. We look forward to offering this new indication of TYVYT (sintilimab injection) and helping to treat people with squamous non-small cell lung cancer in China."

Dr. Yongjun Liu, President of Innovent, stated: "As one of the most life-threatening diseases, cancer has always been a key focus for the pharmaceutical companies, researchers and clinicians that help develop oncology treatments. Innovent is committed to discovering and developing innovative medicines for diseases with unmet medical needs. This approval of TVYYT (sintilimab injection) in a third indication represents another remarkable achievement for our novel, high quality PD-1 inhibitor in cancer treatment. We are very excited about this approval, and we look forward to now offering this as a first-line treatment option for people with squamous non-small cell lung cancer."

Dr. Hui ZHOU, Senior Vice President of Clinical Development of Innovent, stated: "In China, lung cancer has the highest incidence and mortality rate among all tumor types. Although treatment development has been advancing in recent years, there is still a large number of people with lung cancer that lack effective treatment options – particularly those with the squamous type. This new indication of TYVYT (sintilimab injection) provides an additional first-line treatment option for people with squamous non-small cell lung cancer. We are hopeful that TYVYT (sintilimab injection) will help many people with this type of cancer."

Julio Gay-ger, Lilly China President and General Manager, stated: "Oncology is one of the most important strategic therapeutic areas for Lilly. In particular, we have been deeply rooted in lung cancer treatment for many years. We’re excited to see two new indications for TYVYT (sintilimab injection) in combination with two Lilly classic anti-tumor drugs – pemetrexed and gemcitabine, respectively – and platinum chemotherapy as first-line therapy for people with non-small cell lung cancer, both approved this year by the NMPA within a few months of each other. We are committed to the development and commercialization of effective cancer therapies and devote ourselves to helping patients with more innovative products through independent R&D and strategic collaborations."

Dr. Li WANG, Senior Vice President of Lilly China and Head of Lilly China Drug Development and Medical Affairs Center, stated: "Results of multiple clinical studies show that immuno-oncology therapy has become one of the standard global treatment options for lung cancer due to its proven clinical efficacy and safety. The approval of this new indication has further demonstrated its potential to treat people with lung cancer. Lilly will continue to work closely with Innovent to further explore TYVYT’s clinical potential in other tumor types with the hopes of helping more cancer patients."

About Squamous Non-Small Cell Lung Cancer

Lung cancer is a malignancy with the highest morbidity and mortality in China. Non-small cell lung cancer (NSCLC) accounts for about 80 to 85 percent of lung cancer. Approximately 70 percent of people with NSCLC have locally advanced or metastatic disease at initial diagnosis, rendering many of those patients with no chance of radical resection. Meanwhile, even after radical surgery, patients still have a high chance of recurrence and eventually die from disease progression. About 30 percent of people in China with NSCLC have tumors of the squamous subtype and there are limited approved second-line therapies for these patients. Therefore, this remains a huge unmet medical need in China.

About ORIENT-12

ORIENT-12 （ClinicalTrials.gov, NCT03629925）is a randomized, double-blind, Phase 3 clinical trial evaluating TYVYT (sintilimab injection) or placebo in combination with GEMZAR (gemcitabine) and platinum chemotherapy (carboplatin or cisplatin) as a first-line treatment for advanced or metastatic squamous non-small cell lung cancer (sqNSCLC). A total of 357 participants were enrolled and randomized in a 1:1 ratio (179 participants in the TYVYT (sintilimab injection) combination arm, 178 participants in the placebo combination arm).

ORIENT-12 demonstrated a statistically significant improvement in progression-free survival (PFS), the study’s primary endpoint, of TYVYT (sintilimab injection) in combination with GEMZAR and platinum chemotherapy compared with placebo in combination with GEMZAR and platinum chemotherapy. The median PFS of the TYVYT (sintilimab injection) combination arm was 5.5 months compared to 4.9 months on the placebo combination arm (HR=0.536, 95% CI: 0.422-0.681, P< 0.00001) as assessed by Independent Radiographic Review Committee (IRRC), and 6.7 months compared to 4.9 months respectively (HR=0.532, 95% CI: 0.419-0.674, P< 0.00001), as assessed by the study’s investigators. Overall survival (OS), a secondary endpoint, of the TYVYT (sintilimab injection) combination arm showed a positive trend when compared to the placebo combination arm (HR=0.567, 95%CI: 0.353-0.909, P=0.01701), though the data were not yet mature at an interim analysis. The safety profile is consistent with previously reported TYVYT (sintilimab injection) studies, and no new safety signals were identified.

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 Lilly. Sintilimab is a type of 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 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 three 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
Additionally, Innovent currently has regulatory submissions under review in China for sintilimab:

In combination with BYVASDA (bevacizumab injection) for the first-line treatment of hepatocellular carcinoma
The second-line treatment of squamous non-small cell lung cancer
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.

On June 3, 2021 Protagonist Therapeutics ("Protagonist" or "the Company") (Nasdaq: PTGX), reported that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation for its lead investigational new drug candidate, rusfertide, for the treatment of patients with polycythemia vera (PV) for the reduction of erythrocytosis in those patients who do not require further treatment for thrombocytosis and/or leukocytosis (Press release, Protagonist, JUN 3, 2021, View Source [SID1234583611]). Breakthrough Therapy Designation requires that the drug candidate treat a serious or life-threatening disease or condition. It also requires preliminary clinical evidence that indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints. The designation has the potential to expedite the development and regulatory review process.

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"We are thrilled to receive the Breakthrough Therapy Designation for rusfertide in PV, a serious disease where the need for different and better treatment options is clear and pressing," said Suneel Gupta, PhD, Chief Development Officer at Protagonist. "Rusfertide is a natural hormone mimetic and may stand out as the first non-cytoreductive therapeutic drug for PV. We look forward to working closely with FDA regulators to advance and complete all relevant clinical studies, both ongoing and planned, as quickly as possible."

The designation for rusfertide was supported in part by promising data from the ongoing Phase 2 clinical trial in patients with PV, presented at the Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) in 2020. The data showed that when treated with rusfertide, a majority of patients were able to eliminate therapeutic phlebotomies, maintain a target hematocrit level of less than 45 percent, reverse iron deficiency, and experience symptom improvements. The FDA previously granted orphan drug status and Fast Track Designation to rusfertide in PV. Breakthrough Therapy Designation offers additional advantages over Fast Track Designation, including FDA actions to expedite both planned clinical trials and plans for expediting the manufacturing development strategy.

Updated data from the ongoing Phase 2 study has been selected for oral presentation at the upcoming annual meeting of the European Hematology Association (EHA) (Free EHA Whitepaper). This meeting will take place June 9 through 17 and will remain accessible until August 15, 2021.

About FDA Breakthrough Therapy Designation

Breakthrough Therapy Designation is an FDA program intended to expedite the development and regulatory review of investigational therapies that are designed to address serious or life-threatening conditions. The criteria for Breakthrough Therapy Designation requires preliminary clinical evidence that indicates that the candidate may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints. This designation provides the Company with more intensive FDA guidance on an efficient drug development program, and eligibility for other actions to expedite the FDA review, such as a rolling review of a New Drug Application (NDA), where the FDA may review sections of the NDA before the complete application is submitted. An NDA for a product candidate receiving Breakthrough Therapy Designation may also be eligible for priority review if the relevant criteria are met. Breakthrough Therapy Designation does not change the standards for approval. For more information, please visit the FDA website at www.fda.gov.

On June 3, 2021 Histogen Inc. (NASDAQ: HSTO), a clinical-stage therapeutics company focused on developing potential first-in-class restorative therapeutics that ignite the body’s natural process to repair and maintain healthy biological function, reported an update on its pipeline focus following a strategic evaluation of its regenerative medicine platform technology development programs with the goal of focusing on high value orthopedic indications, creating pipeline synergies and maximizing resources in an effort to further drive long-term shareholder value (Press release, Conatus Pharmaceuticals, JUN 3, 2021, View Source [SID1234583445]).

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Development Program Updates

HST 001 – we completed our strategic evaluation of the HST 001 program taking into consideration the results from our Phase 1b/2a clinical trial of HST 001 as announced earlier this year, and as a result, we will suspend development of this program. While HST 001 has demonstrated a favorable safety and tolerability profile in androgenic alopecia in men, the development resources required to potentially achieve an acceptable efficacy threshold are substantial in terms of cost and time. Therefore, we believe the best business decision at this time, is to redirect these resources towards our high value orthopedic programs.
HST 003 – we are on track to initiate our Phase 1/2 clinical study of HST 003 in June 2021. The upcoming study is designed to evaluate the safety and efficacy of human extracellular matrix (hECM) implanted within microfracture interstices and the cartilage defect in the knee to regenerate hyaline cartilage in combination with a microfracture procedure. Patients will be enrolled at three sites: Oasis MD in San Diego, CA, The Steadman Clinic in Vail, CO, and Walter Reed Medical Center in Bethesda, MD.
HST 004 – We recently initiated an investigational new drug application (IND) enabling activities for HST 004, a CCM solution intended to be administered through an intradiscal injection for spinal disc repair. Our initial preclinical research has shown that HST 004 stimulates stem cells from the spinal disc to proliferate and secrete aggrecan and collagen II, regenerate normal matrix and cell tissue structure, and restore disc height. HST 004 was also shown to both reduce inflammation and protease activity and upregulate aggrecan production in an ex vivo spinal disc model. We anticipate filing an IND in the second half of 2022.

Emricasan – In May, we, along with our partner Amerimmune, completed enrollment of the Phase 1 study of emricasan for the treatment of mild-symptomatic COVID-19 patients. A total of 13 patients have been enrolled at our single site in New York City versus the initially targeted 40 patients. The decision to stop enrollment with a lesser number of patients was based solely upon the overall decline in COVID-19 cases in New York City and its negative impact on patient recruitment. To date, there have been no reports of serious adverse events, and we anticipate top-line safety, biomarker and patient reported outcomes data to be available in June 2021.
"Following the completion of our HST 001 Phase 1a/2b study in androgenic alopecia in men in the first quarter of this year, we embarked upon a strategic pipeline evaluation with the goal of determining the optimal value-creating opportunities for our regenerative medicine technology platform," said Richard W. Pascoe, President and Chief Executive Officer. "As a result of our evaluation, we have charted a new course for Histogen with a focus on orthopedic indications that we believe sit at the crossroads of pre-clinical and clinical proof of concept, significant commercial opportunity, and unmet medical needs. Moreover, we believe that by developing products that are therapeutically synergistic, we can be more efficient with our resources and create a strategic pipeline of novel therapeutics that has the potential to create long-term value for the benefit of our shareholders."

On June 3, 2021 VBL Therapeutics (Nasdaq: VBLT) reported a primary endpoint amendment in the OVAL Phase 3 registration-enabling study of VB-111 (Press release, VBL Therapeutics, JUN 3, 2021, View Source [SID1234583462]). The clinical trial amendment included a second, separate primary endpoint, of progression free survival (PFS), in addition to the original primary endpoint of the trial, overall survival (OS). Based upon the changes that were reviewed by the U.S. Food and Drug Administration (FDA), successfully meeting either primary endpoint is expected to be sufficient to support BLA submission. Successful meeting of the PFS endpoint, with a readout anticipated in 2022, could accelerate BLA submission by approximately one year compared to original projections based on the readout of the OS primary endpoint that remains anticipated in 2023. The OVAL study amendment, along with an update on the number of patients enrolled, which as of April 30, 2021, exceeded 260 patients, will be presented tomorrow as part of a virtual Clinical Trial in Progress poster presentation at the 2021 ASCO (Free ASCO Whitepaper) Annual Meeting.

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"The addition of PFS as a second independent primary endpoint has several very important implications on the OVAL study," said Bradley Monk, M.D., FACS, FACOG, Arizona Oncology (U.S. Oncology Network), and Chair of the OVAL Study Steering Committee. "First, it de-risks the study, as it provides two options for study success. Second, it should accelerate the time to clinical readout and to potential approval, as PFS data are expected during 2022. Third, keeping OS as a primary endpoint preserves the opportunity of differentiating VB-111 from current ovarian cancer treatments, which were approved based on PFS data and have not as yet shown an OS benefit."

Title: Clinical Trial in Progress: Pivotal Study of VB-111 Combined with Paclitaxel vs. Paclitaxel for Treatment of Platinum-Resistant Ovarian Cancer (OVAL, VB-111-701/GOG-3018)
Authors: Arend, R.C., et al.
Session: Gynecologic Cancer
Session type: Poster Session
Abstract: 5599

About the OVAL study (NCT03398655)
OVAL is an international Phase 3 randomized pivotal registration enabling clinical trial that compares a combination of VB-111 and paclitaxel to placebo plus paclitaxel, in patients with platinum resistant ovarian cancer. The study is planned to enroll approximately 400 patients. OVAL is conducted in collaboration with the GOG Foundation, Inc., an independent international non-profit organization with the purpose of promoting excellence in the field of gynecologic malignancies.

About VB-111 (ofranergene obadenovec)
VB-111 is an investigational anti-cancer gene-therapy agent that is being developed to treat a wide range of solid tumors. VB-111 is a unique biologic agent that is designed to use a dual mechanism to target solid tumors. Its mechanism combines blockade of tumor vasculature with an anti-tumor immune response. VB-111 is administered as an IV infusion once every 6-8 weeks. It has been observed to be well-tolerated in >300 cancer patients and demonstrated activity signals in an "all comers" Phase 1 trial as well as in three tumor-specific Phase 2 studies. VB-111 has received an Orphan Designation for the treatment of ovarian cancer from the European Commission. VB-111 has also received orphan drug designation in both the US and Europe, and fast track designation in the US, for prolongation of survival in patients with recurrent glioblastoma. VB-111 demonstrated proof-of-concept and survival benefit in Phase 2 clinical trials in radioiodine-refractory thyroid cancer and recurrent platinum-resistant ovarian cancer (NCT01711970)