On January 12, 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, reported with Eli Lilly and Company ("Lilly",NYSE: LLY) that the National Medical Products Administration (NMPA) of China has accepted the supplemental New Drug Application (sNDA) for TYVYT (sintilimab injection) as second-line therapy for squamous non-small cell lung cancer (sqNSCLC) (Press release, Innovent Biologics, JAN 12, 2021, View Source [SID1234573939]). The application is the third sNDA for TYVYT (sintilimab injection) in NSCLC.

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This sNDA was based on a randomized, open-label, Phase 3 clinical trial (ORIENT-3)—evaluating TYVYT (sintilimab injection) as second-line therapy for patients with advanced or recurrent sqNSCLC whose cancer had progressed on first-line platinum-based chemotherapy. Based on the final analysis in the pre-specified full analysis set, TYVYT demonstrated a statistically significant improvement in overall survival (OS) compared with docetaxel, which met the pre-specified superiority criteria. The progression-free survival (PFS) and objective response rate (ORR) were also significantly improved. The safety profile is consistent with previously reported sintilimab studies, and no new safety signals were identified. Detailed data will be released in an upcoming international academic conference or journal.

The principal investigator of ORIENT-3, Professor Yuankai Shi, Associate Dean of Cancer Hospital, Chinese Academy of Medical Sciences, stated: "Lung cancer is the leading cause of cancer death globally, of which NSCLC accounts for 80% to 85%. In the past few decades, drug development of NSCLC has mainly focused on nonsquamous NSCLC, while drug development of squamous NSCLC has been slower due to its unique epidemiological, histopathological and molecular characteristics. In China, the options for second-line immunotherapy are even more limited. The ORIENT-3 study confirmed that the anti-PD-1 monoclonal antibody sintilimab significantly improved OS for the second-line treatment of squamous NSCLC patients, which is of great clinical value. We hope that the positive results of ORIENT-3 can potentially help more squamous NSCLC patients."

"TYVYT (sintilimab injection) is the first anti-PD-1 monoclonal antibody included in the New Catalogue of the National Reimbursement Drug List," said Dr. Hui Zhou, Vice President of Medical Science and Strategy Oncology of Innovent. "In August 2020, the NMPA accepted a new indication application for TYVYT (sintilimab injection) in combination with chemotherapy for first-line treatment of squamous NSCLC. In ORIENT-3 study, sintilimab as second-line monotherapy demonstrated a significantly improved survival benefit for patients with advanced squamous NSCLC, and we look forward to the approval of this indication, to potentially help more patients with this type of lung cancer."

"We are excited about these results, showing TYVYT (sintilimab injection) significantly improved overall survival in this patient population. This study underscores the joint commitment from Lilly and Innovent to provide innovative treatment options to patients with lung cancer," said Dr. Wang Li, Senior Vice President of Lilly China and Head of Lilly China Drug Development and Medical Affairs. "We would like to thank the patients, the investigators, the clinical trial centers and our colleagues from Innovent that are involved in the study. We look forward to working together to potentially bring this new treatment option to patients in China with squamous NSCLC."

About ORIENT-3 Trial

ORIENT-3 is a randomized, open-label, multi-center, Phase 3 clinical trial in China to evaluate the efficacy and safety of TYVYT (sintilimab injection) as second-line therapy for advanced or metastatic sqNSCLC (ClinicalTrials.gov, NCT 03150875). The primary endpoint is overall survival (OS). The secondary endpoints include progression-free survival (PFS) assessed by investigators based on RECIST v1.1, objective response rate (ORR) and safety profile.

A total of 290 patients were enrolled in ORIENT-3 and randomized in a 1:1 ratio to receive either TYVYT (sintilimab injection) 200mg or docetaxel every three weeks. The patients received treatment until radiographic disease progression, unacceptable toxicity or any other conditions that require treatment discontinuation.

About Squamous NSCLC

Lung cancer is a malignancy with the highest morbidity and mortality in China. NSCLC accounts for about 80 to 85 percent of lung cancer. Approximately 70 percent of people with NSCLC have locally advanced or metastatic NSCLC 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 with NSCLC in China have tumors of the squamous subtype and there are limited second-line immunotherapies for these patients. In China, there remains a huge unmet medical need.

About TYVYT (Sintilimab Injection)

TYVYT (sintilimab injection), an innovative drug with global quality standards jointly developed in China by Innovent and Eli Lilly and Company, has been granted marketing approval by the NMPA for the treatment of relapsed or refractory classic Hodgkin’s lymphoma after two lines or later of systemic chemotherapy, and is included in the 2019 Guidelines of Chinese Society of Clinical Oncology for Lymphoid Malignancies. TYVYT was included in the National Reimbursement Drug List (NRDL) in 2019 as the historically first PD-1 inhibitor entering in NRDL and the only PD-1 included in the list in that year.

In April 2020, the NMPA accepted the sNDA for TYVYT (sintilimab injection) in combination with ALIMTA (pemetrexed) and platinum chemotherapy as first-line therapy for the treatment of patients with non-squamous non-small cell lung cancer (NSCLC). In May 2020, TYVYT (sintilimab injection) monotherapy met the primary endpoint of overall survival in the Phase 2 ORIENT-2 study as second-line therapy in patients with advanced or metastatic esophageal squamous cell carcinoma. In August 2020, the NMPA accepted the sNDA for TYVYT in combination with GEMZAR (gemcitabine for injection) and platinum chemotherapy as first-line therapy in squamous NSCLC. In September 2020, TYVYT (sintilimab injection) in combination with BYVASDA (bevacizumab biosimilar injection) as a first-line treatment in advanced hepatocellular carcinoma met the predefined primary endpoints of overall survival and progression-free survival in an interim analysis of the Phase 3 ORIENT-32 study. In January 2021, the NMPA accepted the sNDA for TYVYT as second-line therapy for sqNSCLC.

TYVYT (sintilimab injection), is a type of immunoglobulin G4 monoclonal antibody, which binds to PD-1 molecules on the surface of T-cells, block the PD-1 / PD-Ligand 1 (PD-L1) pathway and reactivate T-cells to kill cancer cells. Innovent is currently conducting more than 20 clinical studies with TYVYT (sintilimab injection) to evaluate its safety and efficacy in a wide variety of cancer indications, including more than 10 registrational or pivotal clinical trials. Meanwhile, Innovent is conducting clinical research studies on TYVYT (sintilimab injection) worldwide.

On January 11, 2021 Synlogic, Inc. (Nasdaq: SYBX), a clinical stage company bringing the transformative potential of synthetic biology to medicine, reported that significant clinical milestones for 2021 and provided an overview of recent progress (Press release, Synlogic, JAN 11, 2021, View Source [SID1234573785]).

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"With three programs in clinical trials, multiple proof of concept opportunities, and a preclinical portfolio advancing rapidly towards the clinic, Synlogic is poised for success with a number of data readouts coming in 2021," said Aoife Brennan, M.B. Ch.B., Synlogic’s President and Chief Executive Officer. "2020 was a year we will not forget. Despite the external challenges, the Synlogic team moved our programs forward with grit and resilience. We enter 2021 with momentum and the opportunity to truly see the potential of novel Synthetic Biotic medicines to make a meaningful difference in patients’ lives."

Synlogic anticipates clinical proof of concept data in 2021 across two metabolic programs, SYNB1618 for the treatment of Phenylketonuria (PKU) and SYNB8802 for the treatment of Enteric Hyperoxaluria, as well as continued advancement of SYNB1891 for the treatment of solid tumors and lymphomas.

Execution Across Clinical Pipeline: Metabolic Programs

Progression of a proof of concept Phase 2 clinical trial of SYNB1618 for the treatment of Phenylketonuria (PKU)
SYNB1618 is an investigational drug composed of a Synthetic Biotic medicine designed to consume phenylalanine (Phe) in the gastrointestinal (GI) tract for the treatment of PKU in patients regardless of age or disease type.
A solid oral formulation of SYNB1618 has been shown to metabolize Phe in the GI tract in a healthy volunteer study.
The SynPheny-1 study evaluates plasma Phe lowering of SYNB1618 in adult PKU patients who do not benefit from, or do not tolerate, existing therapies such as Kuvan or Palynziq.
Synlogic anticipates data from SynPheny-1 will be available mid- 2021.

Progression of a Phase 1 clinical study of SYNB8802 for the treatment of Enteric Hyperoxaluria
SYNB8802 is an investigational drug composed of a Synthetic Biotic medicine designed to consume oxalate in the GI tract and lower urinary oxalate levels, potentially reducing kidney damage due to Enteric Hyperoxaluria.
In data presented at the American Society of Nephrology’s (ASN) 2020 Kidney Week, SYNB8802 was shown to reduce urinary oxalate in two animal models of Hyperoxaluria.
The Phase 1 clinical study evaluates the safety, tolerability, and potential for urinary oxalate lowering in healthy volunteers and patients.
The study has two parts: Part A is a multiple ascending dose study in healthy volunteers; Part B is a placebo controlled, cross-over design study in patients with Enteric Hyperoxaluria following Roux-n-Y gastric bypass surgery which provides an opportunity to demonstrate proof of concept.
Synlogic anticipates data from Part B of the study will be available mid-2021.
Execution Across Clinical Pipeline: Immunomodulation Programs

Advancement of SYNB1891 into combination arm dosing with PDL1 checkpoint inhibitor in ongoing Phase 1 study
SYNB1891 is an investigational drug composed of an intratumorally delivered Synthetic Biotic medicine designed to produce a STING agonist and act as a dual innate immune activator for the treatment of advanced solid tumors and lymphoma.
SYNB1891 is currently being evaluated in a Phase 1 study that has two parts:
Part A is a monotherapy arm that has enrolled four dose cohorts to date.
A maximum tolerated dose has not been reached and dose escalation continues.
Part A of the study has demonstrated target engagement and activation of the STING pathway.
Part B of the study will combine escalating dose levels of SYNB1891 with a fixed dose of the PD-L1 checkpoint inhibitor atezolizumab, to establish a recommended Phase 2 dose for the combination regimen.
Synlogic anticipates additional data from cohorts in both arms will be available in mid to late 2021.
Preclinical Roadmap

Synlogic continues to advance preclinical programs including additional effectors for immune-oncology; immune regulation targets for treatment of inflammatory bowel disease and other inflammatory disorders; and additional undisclosed rare metabolic diseases.
Further updates on these programs will be shared as they advance towards the clinic.
2020 Corporate Milestones

Synlogic strengthened leadership with the following appointments:
Synlogic appointed Dr. David Hava, Ph.D., as Chief Scientific Officer. Dr. Hava brings over a decade of senior experience in research and development to Synlogic, including deep academic expertise in pillars of synthetic biology.
Synlogic promoted Antoine ‘Tony’ Awad to Chief Operating Officer. Mr. Awad brings over 15 years of experience in the biotechnology and pharmaceutical industry with substantial experience in the development and manufacturing of novel therapeutics from pre-IND studies through global commercialization.
Synlogic appointed Michael Heffernan, seasoned entrepreneur and biopharmaceutical leader, and Dr. Michael Burgess, physician scientist and expert in translational development, to its board of directors.
Synlogic and Ginkgo Bioworks advanced their long-term strategic platform collaboration that provides expanded synthetic biology capabilities to Synlogic.
Ginkgo and Synlogic are collaborating on multiple efforts including metabolic and immunomodulation programs, and assessment of the potential application of Synthetic Biotics for vaccine development.
Synlogic ended the third quarter of 2020 with $102.0 million in cash, cash equivalents and short- and long-term investments and expects this will fund company operations through 2022 under its current plan.

On January 11, 2021 Cerus Corporation (Nasdaq: CERS) reported preliminary product revenue for the fourth quarter and full year 2020 and provided 2021 product revenue guidance (Press release, Cerus, JAN 11, 2021, View Source [SID1234573804]).

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Cerus’ unaudited preliminary product revenue for the fourth quarter of 2020 totaled $28.2 million, an increase of 35% over the $20.9 million recognized during the same period in the prior year. Based on its fourth quarter unaudited preliminary product revenue, the Company expects full year 2020 product revenue of $91.9 million, exceeding the Company’s current 2020 product guidance range of $89 million to $91 million. The preliminary product revenue results have not been audited and are subject to change.

Preliminary fourth quarter product revenue would represent the highest quarterly product revenue ever reported by Cerus.

"Despite the challenges that our blood center customers, hospitals and we have faced with the COVID-19 pandemic, demand for INTERCEPT continues to grow impressively. While we anticipate that COVID-19 may still impact our access to blood centers and hospitals in the U.S. and western Europe in 2021, we nonetheless expect to see continued growth in INTERCEPT platelet kit demand, particularly in the U.S. as the new October 1 deadline for compliance with the FDA guidance on bacterial safety approaches," said William ‘Obi’ Greenman, Cerus’ president and chief executive officer.

"2021 will also mark our first sales of a biologic therapeutic product – Pathogen Reduced Cryoprecipitated Fibrinogen Complex. Our initial, limited launch will be a building phase ahead of a much broader, nationally focused rollout we expect in 2022. Based on our interactions and work to date, we are encouraged by the clinician reception to the new product and look forward to introducing the first manufactured products to hospitals for transfusion to patients this year," continued Greenman.

Despite ongoing pandemic-related customer access limitations, the Company expects full year 2021 product revenue will be in the range of $106 million to $110 million, representing growth of approximately 15% to 20% compared to preliminary unaudited 2020 full year results. This growth is expected to be driven by strong platelet kit demand in the U.S., as well as expected continued market adoption in targeted international markets.

Cerus will provide complete fourth quarter and full year 2020 financial results and host a call to discuss both 2020 results and 2021 expectations in late February.

On January 11, 2021, Ideaya Biosciences Presented the corporate presentation (Filing, 8-K, Ideaya Biosciences, JAN 11, 2021, View Source [SID1234573821])

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On January 11, 2021 Propanc Biopharma, Inc. (OTC: PPCB) ("Propanc" or the "Company"), a biopharmaceutical company developing novel cancer treatments for patients suffering from recurring and metastatic cancer, reported that pancreatic proenzymes versus T-Cell therapy when targeting solid tumors such as pancreatic, ovarian and colorectal cancers (Press release, Propanc, JAN 11, 2021, View Source [SID1234573837]). The analysis is prepared by the Company’s Chief Executive Officer, Mr. James Nathanielsz, in collaboration with joint lead researcher, Professor Macarena Perán, from the University of Jaén, Granada, Spain.

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This press release features multimedia. View the full release here: View Source

Cell differentiation therapy using pancreatic proenzymes has shown to degrade the fibrotic tissue on the surface of solid tumors and therefore might impair tumor engrafting, tumor niche formation and even cancer stem cell subpopulation activation. (Photo: Business Wire)
Cell differentiation therapy using pancreatic proenzymes has shown to degrade the fibrotic tissue on the surface of solid tumors and therefore might impair tumor engrafting, tumor niche formation and even cancer stem cell subpopulation activation. (Photo: Business Wire)

"We are making significant inroads in the way we treat cancer today, but there is a genuine need to continually challenge ourselves to improve the standard of care for many cancer types," said James Nathanielsz. "At Propanc, we share a vision to develop and commercialize a novel approach using pancreatic proenzymes for the long-term treatment and prevention of metastatic cancer from solid tumors. Our goal is to reduce the threat of cancer by extending life meaningfully, but not at the expense of great toxicity. This humanitarian cause affects us all."

Everybody knows what cancer is. Cells in the body begin to divide rapidly and uncontrollably in the body, with an ability to migrate from one location and spread to distant sites. However, when a cell becomes undifferentiated, forgetting how to do its job and investing all its energy in proliferating, it becomes cancerous. Unlike normal cells, cancer cells multiply, but do not differentiate. Most common therapies take advantage of the uncontrolled proliferation and kill these cells by targeting the cell division machinery. These therapies are effective, but affect healthy cells as well, particularly those with a high cell turn over, inducing undesirable effects. More recently, scientific advancements have meant that T-cell therapies are considered a tremendous improvement compared to older treatments. T-cell therapy involves using specific T-cells from the patient’s own immune system. Doctors take a type of white blood cell from the patient’s body and genetically change the cells in a lab so they can better find the cancer. Then millions of these target-seeking cells are put back into the patient.

The use of cancer-specific T-cells is a clever strategy to use the natural weapons from the body against cancer cells. This is a genuine targeted therapy, which kills cancer by recognizing antigen targets expressed on the cancer cell surface. This novel strategy is promising, although it still has some challenges. Of most importance is the health of patient’s T-cells, which may decline due to age, or degeneration induced by the cancer itself, which is not ideal. There are also limitations with regards to efficacy and safety, and they are highly expensive. Resistance can develop over time, as specific antigens mutate, causing tumor escape and disease relapse. Furthermore, a patient can have serious side effects, including very high fevers and dangerously low blood pressure days after treatment. Other serious side effects include neurotoxicity, or changes in the brain that cause swelling, confusion, seizures, or severe headaches. Another problem is that T-cells can kill off some of the good B-cells that help fight germs, so the patient may be at higher risk for infection. Finally, when factoring in all the costs associated with T-cell therapies, hospitals may charge as much as $1.5 million or more to avoid losing money.

So, whilst enhancing a patient’s immune response to attack cancer has genuine merit, other ways to stop cancer are needed to further reduce the threat of cancer from a killer disease to a chronic (long term) illness. Another approach to stop cancer is not by targeting cell death, but inducing cell differentiation. This is known as cell differentiation therapy. The key consideration is how to convince the malignant cells to stop proliferating and return to their role as a specific cell type.

So, what are the advantages of cell differentiation therapy over other strategies, like T-Cell therapy? Firstly, cell differentiation therapy does not target cell death, so healthy cells are not compromised. Cell differentiation therapy induces cancer cells to differentiate and become non-proliferative (non-replicating), so they die naturally. Cell differentiation therapy acts not only against cancer cells, but interestingly can turn cancer stem cells (undifferentiated cells) towards completely differentiated, i.e., normal cells. Significantly, once the cancer stem cells are completely differentiated, they are no longer hidden from the immune system. This means that the body’s immune response can more effectively target the cancer, and therefore, in theory, will be complementary to immunological approaches like T-Cell therapy, by improving response rates and reducing toxicity.

More than 100 years ago, a comparative embryologist Professor John Beard first proposed that pancreatic enzymes represent the body’s primary defense against cancer and would prove useful as a cancer treatment. Since then, scientists have endorsed Beard’s hypothesis with encouraging data from patient treatment. After extensive laboratory research over the last decade and limited human testing by compassionate use, there is evidence that pancreatic proenzymes reduces cancer cell growth via promotion of cell differentiation, enhances cell adhesion (cell to cell contact) and suppresses metastasis (cancer spread), has no serious side effects and improves patient survival. The unique approach targets and eradicate cancer stem cells, which can migrate to other organs triggering explosive tumor growth, causing the patient to relapse after standard treatments that do not target non-dividing cells. Eighty percent of cancers are from solid tumors and metastasis is the main cause of patient death, therefore the potential of cell differentiation therapy using pancreatic proenzymes is significant. Given they are derived from natural sources, pancreatic proenzymes are also not cost prohibitive.

There is little doubt that both the T-Cell based and cell differentiation therapy approaches have emerged to address the limited efficacy of chemotherapy and radiation therapy for patients with advanced solid tumors. Although both therapies bear a slight resemblance because they enhance the immune response, they are not comparable by their mode of action. It is also understood the tumor micro-environment promotes the appearance of new cancer stem cells, derived from non-stem cancerous cells by secreting several biomarkers, such as IL6 (interleukin 6), HGF (hepatocyte growth factor), or TGFβ-163 (tumor growth factor beta-163). Consequently, it is critical to impact the tumor micro-environment in order to effectively eradicate the tumor. Cell differentiation therapy using pancreatic proenzymes has shown to degrade the fibrotic tissue on the surface of solid tumors and therefore might impair tumor engrafting, tumor niche formation and even cancer stem cell subpopulation activation.

Whilst T-Cell therapy has helped to advance the treatment of cancer, there are new and exciting approaches which are complementary and may provide a long-term solution to the treatment and prevention of metastatic cancer from most common solid tumors. Cell differentiation therapy using pancreatic proenzymes is based on the original work by John Beard, a professor of embryology at Edinburgh University over 100 years ago, using fresh pancreatic extracts. Through advancements in science and technology, there is an opportunity to introduce an improved version of this hypothesis, as a long-term therapeutic approach to treat metastatic cancer from solid tumors, which today, remains the main cause of patient death for sufferers.

Bibliography

"Antitumor efficacy of chymotrypsinogen and trypsinogen," P. Hernández, E. López-Ruiz, M. A. García, J. A. Marchal, J. Kenyon, M. Perán.
"In vitro treatment of carcinoma cell lines with pancreatic (pro)enzymes suppresses the EMT programme and promotes cell differentiation", M. Perán, J.A. Marchal, M.A. García, J. Kenyon & D. Tosh.
"A formulation of pancreatic proenzymes provides potent anti-tumour efficacy: a pilot study focused on pancreatic and ovarian cancer", M. Perán, E. López-Ruiz, M. A. García, S. Nadaraia-Hoke, R. Brandt, J. A. Marchal & J. Kenyon.
"Pancreatic proenzymes treatment suppresses BXPC-3 pancreatic Cancer Stem Cell subpopulation and impairs tumour engrafting," P. Hernández-Camarero, E. López-Ruiz, C. Griñán-Lisón, M.A. García, C. Chocarro-Wrona, J.A. Marchal, J. Kenyon & M. Perán.
"Trypsinogen and Chymotrypsinogen: Potent Anti-Tumour Agents," A. González-Titos, P. Hernández-Camarero, S. Barungi, J.A. Marchal, J. Kenyon & M. Perán. *
*Draft manuscript under review