On January 18, 2022 Akeso reported that Ligufalimab combined with Ivonescimab has obtained approval from the Center for Drug Evaluation (CDE) of the National Medical Products Administration of the People’s Republic of China (”China”) to initiate a Phase Ib/II clinical trial with or without chemotherapy for the treatment of advanced malignant tumors, with an aim to evaluate the safety, tolerability, pharmacokinetics, immunogenicity and anti-tumor activity of Ligufalimab combined with Ivonescimab combined with or without chemotherapy for the treatment of advanced malignant tumors (Press release, Akeso Biopharma, JAN 18, 2022, View Source [SID1234605606]).

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The main target subjects of the phase II clinical trial were patients with gastrointestinal tumors. Previously, a phase Ib/II clinical trial of Ligufalimab combined with Ivonescimab has been initiated with main target subjects of patients with head and neck malignant tumors.

Related statistics have shown that malignant tumors have become the major cause of death in the population of China, where deaths from malignant tumors account for approximatelyn23.91% of deaths from all causes of the population. The five-year relative survival rate of malignant tumors in China is approximately 40.5%, which is still far from developed countries. In addition, gastrointestinal tumors account for six out of the top ten death rate of advanced malignant tumors. Among which, treatments for advanced gastric cancer, biliary malignant tumors, pancreatic cancer and other common gastrointestinal tumors are limited and the efficacy is not high, resulting in a huge gap of clinical demand.

Related studies have shown that Ivonescimab can simultaneously stimulate anti-tumor immune response and inhibit tumor angiogenesis through activation of T cells. Since the over-expression of VEGF in the tumor microenvironment has immunosuppressive effects, the use of a bi-specific antibody that blocks both PD-1 and VEGF can achieve synergistic anti-tumor effects of PD-1/PD-L1 antibodies and anti-VEGF antibodies. It is expected to achieve good clinical efficacy and safety. Currently, anti-PD-1/PD-L1 antibody drugs on the market or under research combined with chemotherapy has shown certain clinical benefits for gastrointestinal tumors. For non-small cell lung cancer and hepatocellular carcinoma, the combination of anti-PD-1/PD-L1 antibodies with anti-VEGF antibodies has shown notable synergistic effects.

Related studies have also shown that combination therapy with anti-PD-1 drugs and targeted CD47 drugs yields synergistic antitumor effect through activation of both innate and adaptive immune response, and has demonstrated satisfactory anti-tumor effect in some of the patients with solid tumors with no additional safety risk. CD47 up-regulation can inhibit the phagocytosis of macrophages and the anti-tumor effect of VEGF/VEGFR inhibitors. At the same time, anti-VEGF/VEGFR treatment can also induce CD47 up-regulation, thereby inhibiting the anti-tumor function of macrophages. Therefore, blocking both VEGF and CD47 can effectively inhibit the immunosuppressive pathway induced by anti-angiogenesis therapy (CD47 up-regulation) while enhancing the phagocytosis of macrophages to improve the anti-tumor efficacy.

Therefore, the combination therapy of Ligufalimab and Ivonescimab is expected to activate both innate and adaptive immune pathways, so to achieve the synergistic effect of inhibiting the three tumor immune targets of PD-1, VEGF and CD47 through the combination of the two drugs, thus achieving better anti-tumor effects as compared with existing therapies. Furthermore, based on the statistics of the in vitro and in vivo pharmacodynamics and toxicology studies of Ligufalimab and Ivonescimab, the anti-tumor activity and the controlled safety profile in several clinical trials of different types of tumors, it is expected that the combination of Ivonescimab and Ligufalimab and/or chemotherapy will have a positive effect for the treatment of gastrointestinal tumors.

Currently, Ivonescimab has taken the lead in entering the phase III clinical trial globally, and Ligufalimab is also one of the world’s leading CD47 monoclonal antibodies in clinical research and development progress. The clinical trial of Ligufalimab combined with Ivonescimab in the treatment of head and neck malignant tumors and gastrointestinal tumors is another embodiment of the Company’s continuous exploration of the clinical and commercial value of its rich drug pipeline.

On January 18, 2022 I-Mab reported that the first patient has been dosed in its China Phase II trial of lemzoparlimab in combination with the PD-1 antibody toripalimab (TUOYI) in patients with advanced solid tumors (Press release, I-Mab Biopharma, JAN 18, 2022, View Source [SID1234605605]). The phase 2 study is designed as a basket trial and could potentially lead to a registrational trial in China.

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"We are pleased to initiate the phase 2 trial for the combination of lemzoparlimab and toripalimab in patients with advanced solid tumors in China, and looking forward to accelerating its clinical development," said Dr. Andrew Zhu, President at I-Mab. "We are leveraging our translational medicine findings to select tumors with a higher probability of success for this trial."

Lemzoparlimab is a novel CD47 antibody that exerts strong anti-tumor activity while exhibiting minimal binding to red blood cells based on pre-clinical data. It is being evaluated in combination with pembrolizumab (Keytruda) in advanced solid tumors in the U.S. and in patients with NHL and AML/MDS in other ongoing clinical studies in the U.S. and China. In all clinical trials conducted so far, lemzoparlimab has been administered without a priming dose.

About CD47 and Lemzoparlimab

CD47 is a cell surface protein over-expressed in a wide variety of cancers and can act to protect tumors by delivering a "don’t eat me" signal to otherwise tumor-engulfing macrophages. CD47 antibody blocks this signal and enables macrophages to attack tumor cells. However, development of CD47 antibody as a cancer therapy has been hampered by its hematologic side effects, such as severe anemia, caused by natural binding of CD47 antibody to red blood cells. Scientists at I-Mab discovered a novel CD47 antibody, lemzoparlimab, that is designed to target tumor cells while exerting a minimal untoward effect on red blood cells.

Multiple clinical studies are ongoing in both the U.S. and China to explore indications in treating both hematologic malignancies and solid tumors. Lemzoparlimab is being studied in patients with myelodysplastic syndrome (MDS), acute myelocytic leukemia (AML), and advanced solid tumors in combination with chemotherapy and immune checkpoint inhibitors in the U.S. and China. Combined clinical results from these studies could potentially support future registrational trials in China.

In September 2020, I-Mab and AbbVie entered into a global strategic collaboration to develop and commercialize lemzoparlimab. This includes the design and conduct of further clinical trials to evaluate lemzoparlimab in multiple cancers in China and globally. AbbVie has assumed sponsorship of the U.S. study as of April 2021.

On January 18, 2022 Turning Point Therapeutics, Inc. (NASDAQ: TPTX), a precision oncology company developing next-generation therapies that target genetic drivers of cancer, reported updates and anticipated milestones across its 2022 strategic objectives (Press release, Turning Point Therapeutics, 18 18, 2022, View Source [SID1234605604]).

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"As we look to 2022, we are focused on continuing progress across our clinical stage pipeline and expanding our discovery engine," said Athena Countouriotis, M.D., president and CEO. "We are encouraged that all six cohorts in our registration enabling TRIDENT-1 study for our lead drug candidate repotrectinib continue to enroll at a strong pace and we look forward to providing topline BICR data from the ROS1-positive NSCLC cohorts in the second quarter of this year. With our strong balance sheet and organizational growth and leadership, we are well positioned to continue to make rapid progress across our entire portfolio."

The company’s key strategic priorities are:

1. ADVANCE REPOTRECTINIB PROGRAM

The company announced today that the Phase 2 registration enabling TRIDENT-1 study had strong progress across all cohorts for enrollment during the fourth quarter of 2021 with expansion cohort 4 (EXP-4 — ROS1-positive advanced NSCLC population pretreated with one prior TKI without chemotherapy) now fully enrolled with the targeted 60 patients. Enrollment across all six cohorts of the study remains open and continues to progress steadily. Enrollment in EXP-4 is ongoing to provide continued access to new patients.

Data from ROS1-positive TKI-naïve NSCLC patients in the Phase 1 portion of the TRIDENT-1 trial continue to demonstrate best-in-class potential. The duration of response (DOR) for 6 responder patients, among a total of 7 patients treated at or above the recommended Phase 2 dose, ranged from 5.6 to 42.2+ months with 3 patients who had DOR of greater than 30 months. DOR was calculated using blinded independent central review (BICR) assessments as of the data cut-off date of July 22, 2019 followed by physician assessments as of the data cut-off date of November 29, 2021. Duration of treatment for the 7 patients ranged from 10.9 to 45.8+ months with 4 out of 7 patients remaining on treatment for greater than 3 years as of the data cut-off date of November 29, 2021.

The company anticipates discussing with the U.S. Food and Drug Administration (FDA) topline BICR data from all of the ROS1-positive NSCLC cohorts from TRIDENT-1 at a pre-NDA meeting in the second quarter of 2022.The company plans on reporting the BICR results, including both objective response rate (ORR) and DOR, in the second quarter of 2022 prior to the pre-NDA meeting.

The company anticipates providing a clinical data update from the NTRK-positive advanced solid tumor cohorts from TRIDENT-1 in the second half of 2022.

2. ADVANCE OTHER PIPELINE PROGRAMS

ELZOVANTINIB (TPX-0022), MET/SRC/CSF1R INHIBITOR

Patient enrollment continues in the SHIELD-1 study at 40 mg QD to 40 mg BID in Phase 1 dose expansion and in parallel elzovantinib also is being studied at an intermediate dose level (60 mg QD to 60 mg BID) in Phase 1 dose escalation.
The company anticipates providing a clinical data update from the Phase 1 SHIELD-1 study in the second half of 2022.
The company anticipates initiating the Phase 2 portion of the SHIELD-1 study in the second half of 2022, pending FDA feedback on data from the intermediate dose level.

The company anticipates initiating the SHIELD-2 combination study of elzovantinib and aumolertinib in mid-2022, pending clearance of an investigational new drug (IND) application by the FDA.

Aumolertinib is EQRx, Inc.’s drug candidate targeting EGFR, and the combination of aumolertinib and elzovantinib will be studied in this Phase 1b/2 trial in patients with EGFR mutant MET-amplified advanced NSCLC who have progressed following treatment with osimertinib. The study will evaluate the safety, tolerability and preliminary efficacy of the combination regimen.
TPX-0046, RET INHIBITOR

The company continues to progress the dose-finding portion of the Phase 1/2 SWORD-1 study, where the company is evaluating multiple doses and schedules to further characterize the pharmacokinetics, safety, and efficacy profile before determining the RP2D.
TPX-0131, ALK INHIBITOR

The dose finding portion of the Phase 1/2 FORGE-1 study is ongoing. The company anticipates providing early interim data from initial patients treated in the dose-finding portion of the FORGE-1 study in the fourth quarter of 2022 or early 2023.
3. ADVANCE RESEARCH PROGRAMS

The company remains on track to nominate two development candidates in the second half of 2022. The company currently has four internal discovery programs targeting aberrant GTPase signaling known to drive genomically defined cancers with significant unmet medical need. The most advanced programs target KRAS G12D and the p21 activated kinase, or "PAK" family.

The company also plans on providing details on the other 2 GTPase signaling discovery programs during the second half of 2022.
FINANCIAL UPDATE

Based on its current operating plans, the company expects that its cash, cash equivalents and marketable securities of $975-985 million as of December 31, 2021 (unaudited), are sufficient to fund current operations into the second half of 2024.

On January 18, 2022 TC BioPharm reported that Executive Chairman and Founder, Dr. Michael Leek will be participating in Advanced Therapies Week in Miami, Florida January 25-28 (Press release, TC Biopharm, JAN 18, 2022, View Source [SID1234605603]).

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Michael will participate in a session titled, Treating Cancer and Covid – Use of Banked Allogeneic Gamma-Delta T Cells in Oncology and Severe Viral Infection. The presentation will take place on Friday January 28th at 9:50 am ET at the Miami Beach Convention Centre. For more information or to register for the event, please visit; View Source

Dr. Michael Leek has 30 years’ experience in regenerative medicine, during which he progressed 10 different cell-based products from the laboratory into clinic. In 2017, Michael received the ‘Scottish Life-Sciences Entrepreneurial Business Leadership’ award for 2016-2017. Michael is also a Fellow of the Royal Society of Medicine and Honorary Lecturer at the University of Aberdeen, School of Medical Sciences.

Advanced Therapies Week is a large and immersive expo for companies in the cell and gene therapy sector. It has a focus on knowledge sharing, relationship building and deal making to advance a major pillar of medicine.

On January 18, 2022 – Transgene (Euronext Paris: TNG), a biotech company that designs and develops virus-based immunotherapeutics against cancer, and PersonGen BioTherapeutics, a Chinese biotech company at clinical trial stage, which is developing breakthrough and innovative CAR-T cell therapies for solid tumors and hematologic tumors, reported a strategic collaboration to evaluate the feasibility and efficacy of combination therapy associating PersonGen’s TAA06 CAR-T cell injection with intravenous (IV) administration of an armed oncolytic virus, from Transgene’s Invir (Press release, Transgene, 18 18, 2022, View Source [SID1234605602]). IO platform, in solid tumors including pancreatic cancer and brain glioma. The collaboration aims to demonstrate the combination’s likely synergistic mechanisms to potentiate CAR-T cell therapy.

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Under the terms of the collaboration agreement, Transgene will develop multiple new OV
candidates, using its patented oncolytic virus backbone VVcopTK-RR- and its Invir.IO technology
platform, specifically for IV administration in combination with PersonGen’s TAA06 CAR-T
injection. PersonGen will evaluate the efficacy of the combination to eliminate solid tumors in
preclinical models.

While CAR-T cell drugs have achieved great success in the treatment of hematological tumor
therapies, there are many clinical challenges with the use of these novel therapies to treat solid
tumors. One of the most critical obstacles is that the solid tumor microenvironment not only
obstructs the homing of CAR-T cells, but also inhibits CAR-T cells’ function. In addition, the high
heterogeneity of solid tumors also facilitates immune escape from CAR-T cell therapy.
TAA06, has been independently developed by PersonGen, which has filed an investigational new
drug (IND) application for this novel CAR-T therapy in China and will initiate the IND in the US later
this year. Preclinical studies with TAA06, including pharmacodynamic data have shown superior
in vivo and in vitro therapeutic efficacy in solid tumors.

Patented VVcopTK-RR- oncolytic viruses developed with Transgene’s Invir.IO platform are able to:
• selectively replicate in cancer cells leading to tumor lysis; effectively release antitumor payloads into the tumor;
• stimulate an immune response locally in the tumor, thus optimizing the safety profile
of the virus with the added potential to transform a "cold" tumor into a "hot" tumor.
Clinical and preclinical data has demonstrated that after IV administration, VVcopTK-RR- oncolytic
viruses selectively replicate and persist in tumor cells leading to the local expression of its
functional payload*
.
Based on these highly supportive data, Transgene and PersonGen believe that combining
Transgene’s OV and PersonGen’s CAR-T therapies could overcome the challenges of solid tumor
heterogeneity by improving the tumor microenvironment.