On March 29, 2021 Jacobio Pharmaceuticals (1167.HK) reported its first annual results after its Hong Kong listing (Press release, Jacobio Pharmaceuticals, MAR 29, 2021, View Source [SID1234577304]). By the end of December 31, 2020, its annual revenue was 486 million yuan and R&D expenses exceeded 230 million yuan and increased 66% compared to 2019. As a clinical-stage biotech company, Jacobio has made progress in a number of its pipelines.

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Jacobio focuses on in-house research and development of global first-in-class drugs. Its pipelines target critical cancer cellular pathways, including RAS, MYC, RB, I/O, etc.. Jacobio has expertise in developing allosteric inhibitors against protein tyrosine phosphatase, KRAS and transcriptional factors.

Jacobio generated revenue through licensing out its SHP2 inhibitors to a global partner. "As a clinical-stage biotech company, this licensing deal shows our in-house R&D capabilities," said Dr. Wang Yinxiang, Founder, Chairman and CEO of Jacobio. "We hope to launch our drugs as soon as possible with our partner, to benefit more patients, and realise our commercial value."

Besides SHP2 inhibitors, the clinical-stage pipelines of Jacobio also include the KRAS G12C inhibitor JAB-21000, and BET inhibitor JAB-8263. IND (investigational new drug) applications have been submitted. Five other programs are in the IND-enabling stage.

In terms of the operations, Jacobio’s number of employees has expanded from 130 to about 180 employees in 2020, and the number will continue to grow in 2021. The 20,000 square meter GMP factory in Beijing is under construction and is expected to be completed before the end of 2023. Jacobio has a R&D center with a clinical team in Boston. The Shanghai office will be put into operations in the first half of 2021.

Jacobio was listed on the Hong Kong Stock Exchange Main Board in December 2020 and raised nearly US$200 million (CNY1.3 billion). The company was officially included in the Hang Seng Composite Index on March 15, 2021, and enrolled into the Shenzhen-Hong Kong Stock Connect trading list.

"In 2021, Jacobio will continue investing in R&D. We expect more partnerships with global MNCs to enhance all aspects of drug R&D capabilities, and obtain more global presence," said Dr. Wang Yinxiang.

For more information, please refer to the company’s 2020 annual results announcement published on the Hong Kong Stock Exchange and the company’s official website.

On March 29, 2021 The Menarini Group reported that it has entered into an exclusive license agreement for the development and commercialization of ELZONRIS (tagraxofusp) in the territory of Japan with Nippon Shinyaku Co., Ltd. ELZONRIS is approved for the treatment of patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN) by the U.S. Food and Drug Administration and the European Medicines Agency (Press release, Menarini, MAR 29, 2021, View Source [SID1234577303]).

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BPDCN is a rare, aggressive hematologic malignancy with historically poor outcomes. ELZONRIS (tagraxofusp) is the first approved treatment for patients with BPDCN, and the first approved CD123-targeted therapy, in both the United States and Europe. Elzonris was originally developed by Stemline Therapeutics, now part of the Menarini Group.

"Partnering with Nippon Shinyaku marks another important step forward in our effort to meet the needs of patients with difficult-to-treat diseases and underscores our commitment to delivering innovative medicines for people around the globe," commented Elcin Barker Ergun, CEO of the Menarini Group. "Patients with BPDCN have limited treatment options and we are excited to be collaborating closely with Nippon Shinyaku to make ELZONRIS (tagraxofusp) available to patients in Japan."

"Nippon Shinyaku’s focus and expertise in hematologic malignancies makes the company an excellent partner for ELZONRIS (tagraxofusp)," commented Ivan Bergstein, M.D., President and CEO of Stemline Therapeutics, now part of the Menarini Group. "Through this development and commercial partnership, we look forward to advancing ELZONRIS as a potential new treatment option for patients suffering from BPDCN."

About ELZONRIS in the European Union

ELZONRIS (tagraxofusp) is indicated as monotherapy for the first-line treatment of adult patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN). ELZONRIS should be administered under the supervision of a physician experienced in the use of anti-cancer agents.

About ELZONRIS in the USA

ELZONRIS (tagraxofusp), a targeted therapy directed to CD123, is approved by the U.S. Food and Drug Administration (FDA) and commercially available in the U.S. for the treatment of adult and pediatric patients, two years or older, with BPDCN. For full prescribing information in the U.S., visit www.ELZONRIS.com.

ELZONRIS is also being evaluated in additional clinical trials in other indications, including chronic myelomonocytic leukemia (CMML), myelofibrosis (MF), acute myeloid leukemia (AML), and others are planned.

About BPDCN

BPDCN, formerly blastic NK-cell lymphoma, is an aggressive hematologic malignancy, often with cutaneous manifestations, with historically poor outcomes. BPDCN typically presents in the bone marrow and/or skin and may also involve lymph nodes and viscera. The BPDCN cell of origin is the plasmacytoid dendritic cell (pDC) precursor. The diagnosis of BPDCN is based on the immunophenotypic diagnostic triad of CD123, CD4, and CD56, as well as other markers. The World Health Organization (WHO) termed this disease "BPDCN" in 2008; previous names included blastic NK cell lymphoma and agranular CD4+/CD56+ hematodermic neoplasm. For more information, please visit the BPDCN disease awareness website at www.bpdcninfo.com.

About CD123

CD123 is a cell surface target expressed on a wide range of malignancies including blastic plasmacytoid dendritic cell neoplasm (BPDCN), certain myeloproliferative neoplasms (MPNs) including chronic myelomonocytic leukemia (CMML) and myelofibrosis (MF), acute myeloid leukemia (AML) (and potentially enriched in certain AML subsets), myelodysplastic syndrome (MDS), and chronic myeloid leukemia (CML). CD123 has also been reported on multiple myeloma (MM), acute lymphoid leukemia (ALL), hairy cell leukemia (HCL), Hodgkin’s lymphoma (HL), and certain Non-Hodgkin’s lymphomas (NHL). In addition, CD123+ cells have been detected in the tumor microenvironment of several solid tumors as well as in certain autoimmune disorders including cutaneous lupus and scleroderma.

Important Safety Information from EU SmPC

Warnings and precautions

Capillary leak syndrome (CLS), including life-threatening and fatal cases have been reported with most events occurred during the first five days of the first cycle of treatment. Before initiating therapy, it should be ensured that patients have adequate cardiac function and serum albumin ≥ 3.2 g/dL. During treatment, serum albumin levels should be monitored prior to the initiation of each dose, or more often as clinically indicated. Additionally, patients should be assessed for other signs/symptoms of CLS. Patients should be made aware of identifying CLS symptoms and when to seek immediate medical attention. Intravenous albumin supplementation and dosing interruptions may be required.
Severe hypersensitivity reactions have been reported with ELZONRIS.
Thrombocytopenia and neutropenia have been reported in patients treated with ELZONRIS monotherapy. The majority of events were reported in cycle 1 and cycle 2 of treatment, were not dose-limiting and did not recur in subsequent cycles.
ELZONRIS can cause tumour lysis syndrome (TLS).
Treatment with ELZONRIS has been associated with elevations in liver enzymes. Acute hepatic failure and liver encephalopathy has been reported in a patient treated with ELZONRIS at a higher dose (16 mcg/kg).
Summary of the Safety Profile

The most serious adverse reaction that may occur during ELZONRIS treatment is CLS which was reported in 18% of patients with a median time to onset of CLS of 6 days.
Adverse reactions occurring in ≥ 20% of patients treated with ELZONRIS were hypoalbuminemia, increased transaminases, thrombocytopenia, nausea, fatigue and pyrexia.
Adverse reactions grade 3 and above according to the Common Terminology Criteria for Adverse events (CTCAE) and occurring in > 5% of patients were increased transaminases, thrombocytopenia and anaemia.

On March 29, 2021 GT Biopharma, Inc. (NASDAQ: GTBP), a clinical stage immuno-oncology company focused on developing innovative therapeutics based on the Company’s proprietary NK cell engager (TriKE) protein biologic technology platform reported that Dr. Jeffrey S. Miller, M.D., Deputy Director of the Masonic Cancer Center at the University of Minnesota and GT Biopharma’s Consulting Chief Medical Officer, presented updated interim Phase I/II clinical trial results for the Company’s lead therapeutic candidate, GTB-3550 TriKE, being evaluated for the treatment of high-risk myelodysplastic syndromes (MDS) and refractory/relapsed acute myeloid leukemia (AML) at the Innate Killer Summit 2021, held March 23-25 (Press release, GT Biopharma, MAR 29, 2021, View Source [SID1234577302]). Dr. Miller’s presentation "NK Cell Therapeutics: Off-the-shelf Strategies to Increase Activity and Specificity" highlighted the clinical power of immune engagement with Interleukin-15 (IL-15) containing TriKEs.

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Highlights of GT Biopharma’s updated interim GTB-3550 TriKE Phase I/II clinical trial results included:

Up to 63.7% Reduction in Bone Marrow Blast Levels
Restores Patient’s Endogenous NK Cell Function, Proliferation and Immune Surveillance
No Progenitor-derived or Autologous/Allogenic Cell Therapy Required
No Cytokine Release Syndrome Observed
3 out of the Last 5 Patients Treated (25mcg/kg/day to 100mcg/kg/day) Respond
Reduction in Bone Marrow Blast Levels Achieved

To date, 9 patients have been enrolled in the Phase I/II Expansion clinical trial. Patients enrolled early in the Study (patients 1-4) were treated with doses of GTB-3550 below the anticipated therapeutic dose (RP2D) and maximum tolerated dose (MTD) to address possible safety concerns. All patients treated at the lower doses exhibited no signs of toxicity, and did not experience any Grade of Cytokine Release Syndrome (CRS).

Patients 5-9 were treated with increasing doses of GTB-3550 (25mcg/kg/day, 50mcg/kg/day and 100mcg/kg/day, respectively). Three of the five patients (60%) experienced reduction in bone marrow blasts with two patients (one patient treated at the 50mcg/kg/day dose level and one patient treated at the 100mcg/kg/day dose level) experiencing significant reductions in bone marrow blast levels. As previously reported, Patient 7 treated at the 50mcg/kg/day dose level achieved a 61.7% reduction in bone marrow blast levels from 12% before therapy to 4.6% after GTB-3550 therapy. Patient 9 treated at the 100mcg/kg/day dose level achieved a 63.7% reduction in bone marrow blast levels from 22% before therapy to 8% after therapy. All patients treated at these higher doses of GTB-3550 did not experience any Grade of Cytokine Release Syndrome (CRS).

No Cytokine Release Syndrome (CRS) Observed

All patients treated to date with GTB-3550 TriKE displayed no signs of any Grade of cytokine release syndrome (CRS). Of particular note, GTB-3550 is currently being administered to patients at doses significantly higher than the reported MTD (Maximum Tolerated Dose) for continuous infusion of recombinant human IL-15 (Interleukin-15) (Waldmann, TA et al, Clin Cancer Res. (2019) 25:4945–54). GTB-3550 is a single-chain, tri-specific scFv recombinant fusion protein conjugate composed of the variable regions of the heavy and light chains of anti-CD16 and anti-CD33 antibodies, and a modified form of IL-15.

Improved NK Cell Function, Proliferation & Persistence

Correlative studies have shown reproducible endogenous ("native") NK cell activity in all patients. NK cell activation increases early during treatment. This finding correlated with an increase proportion and absolute number of NK cells during treatment. Targeted delivery of IL-15 to NK cells via GTB-3550 TriKE showed preferential proliferation of NK cells and significantly less effect on CD8+ and CD4+ T-cells. We also observed no CD16 shedding by patients’ NK cells, and saw enhanced HL-60 AML target cell killing. This data indicates GTB-3550 TriKE rescues the patient’s exhausted/inhibited endogenous NK cells resulting in their activation, proliferation and persistence.

Mr. Anthony Cataldo, the Chairman and Chief Executive Officer of GT Biopharma commented: "We are pleased with the continued clinical performance of our lead GTB-3550 TriKE product candidate as we continue dose escalation." Mr. Cataldo further stated "this data indicates GTB-3550 therapy demonstrates significant bone marrow blast level reductions in AML and MDS patients without the need for expensive progenitor-derived or autologous/allogenic cell therapies. Further, we have yet to see toxicity (CRS -Cytokine Release Storm) or any significant side effects, as is customary with Cell Therapies and other NK Engagers. We believe as we continue to dose escalate GTB-3550 TriKE, more patients will experience greater clinical efficacy. TriKE’s ability to work in the patient without outside supplemental engineered NK cells or the need for any combination drugs, sets TriKE apart from other cancer therapies. This is also the reason why TriKE therapy will be significantly less expensive than other treatments, opening the door to an off-the-shelf therapeutic."

About High-Risk Myelodysplastic Syndromes (MDS)

MDS is a rare form of bone marrow-related cancer caused by irregular blood cell production within the bone marrow. As a result of this irregular production, MDS patients do not have sufficient normal red blood cells, white blood cells and/or platelets in circulation. High-risk MDS is associated with poor prognosis, diminished quality of life, and a higher chance of transformation to acute myeloid leukemia. Approximately 40% of patients with High-Risk MDS transform to AML, another aggressive cancer with poor outcomes.

About Acute Myeloid Leukemia (AML)

Acute myeloid leukemia (AML) is a type of cancer in which the bone marrow makes abnormal myeloblasts (a type of white blood cell), red blood cells, or platelets. According to the National Cancer Institute (NCI), the five-year survival rate is about 35% in people under 60 years old, and 10% in people over 60 years old. Older people whose health is too poor for intensive chemotherapy have a typical survival of five to ten months. AML accounts for roughly 1.8% of cancer deaths in the United States.

About GTB-3550 TriKE

GTB-3550 is the Company’s first TriKE product candidate being initially developed for the treatment AML. GTB-3550 is a single-chain, tri-specific scFv recombinant fusion protein conjugate composed of the variable regions of the heavy and light chains of anti-CD16 and anti-CD33 antibodies and a modified form of IL-15. The natural killer (NK) cell stimulating cytokine human IL-15 portion of the molecule provides a self-sustaining signal that activates NK cells and enhances their ability to kill. We intend to study GTB-3550 in CD33 positive leukemias such as acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and other CD33+ hematopoietic malignancies.

About GTB-3550 TriKE Clinical Trial

Patients with CD33+ malignancies (primary induction failure or relapsed AML with failure of one reinduction attempt or high-risk MDS progressed on two lines of therapy) age 18 and older are eligible (NCT03214666). The primary endpoint is to identify the maximum tolerated dose (MTD) of GTB-3550 TriKE. Correlative objectives include the number, phenotype, activation status and function of NK cells and T cells.

On March 20, 2021 BioEclipse Therapeutics (BioEclipse), a private clinical-stage biopharmaceutical company with a proprietary platform for developing next-generation cancer immunotherapies, reported that Pam Contag, Ph.D., President and Chief Executive Officer of BioEclipse, will present at the Spring 2021 virtual meeting of the Oncology Investor Conference, sponsored by the National Foundation for Cancer Research, taking place March 29, 2021 to April 1, 2021 (Press release, BioEclipse Therapeutics, MAR 29, 2021, View Source [SID1234577301]). The virtual presentation will be available for all registered attendees.

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During the presentation, Dr. Contag will provide an overview of BioEclipse’s business and recent achievements, as well as the company’s clinical program for its lead drug candidate, CRX100. BioEclipse has initiated an open-label, Phase 1, dose-escalation study to evaluate the safety, tolerability, and pharmacokinetic (PK) properties of CRX100 in advanced solid tumors that do not respond to standard of care, including triple-negative breast cancer, colorectal cancer, hepatocellular carcinoma, osteosarcoma, epithelial ovarian cancer, and gastric cancer.

Members of the BioEclipse management team will also be available to participate in virtual one-on-one meetings with investors and who are registered to attend the conference. Following the conclusion of the event, a recording of Dr. Contag’s presentation will be available under "Recent Presentations" in the Investors section of the Company’s website at www.cytocom.com.

On March 29, 2021 Therapeutic Solutions International, Inc., (OTC Markets: TSOI), reported new data and a new patent filing demonstrating this new immunotherapy derived from inducible pluripotent stem cells (iPSC) induces potent and selective killing of cancer associated blood vessels (Press release, Therapeutics Solutions International, MAR 29, 2021, View Source [SID1234577300]).

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In contrast to other approaches, the current immunotherapy involves transfection of the enzyme alpha1,3-galactosyltransferase into the iPSC, following that iPSC cells are transformed into tumor endothelial-like cells and used for immunization. The introduction of the alpha1,3-galactosyltransferase gene causes the cells to express to Gal alpha 1-3Gal beta-4-GlcNAc (alpha Gal). Alpha Gal is one of the most potent immune stimulating molecules in nature, evoking one of the most potent immune responses known to man.

"Previous immunotherapies activate and recruit approximately 1 out of 1,000,000 immune cells to attack cancer whereas the current approach activates as much as 1 out of 100 immune cells," said Dr. James Veltmeyer, Chief Medical Officer of the Company. "It is well known in the field of xenotransplantation that humans possess 1 to 5% of their antibodies directed towards the alpha Gal epitope which is found in all animals with the exception of monkeys and humans. This is God’s way of stopping inter-species transplantation. By directing this potent antibody response against tumor blood vessels our preliminary data supports feasibility of this novel approach in attacking the Achilles heel of cancer, which is angiogenesis."

Side by side comparison between the currently described approach and approaches, such as placental derived cancer endothelial vaccines like ValloVax by Batu Biologics, suggest significantly higher level of immunity towards cancer angiogenesis can be obtained with the currently described approach.

"The advantage of using iPSC technology is that we are generating consistent and reproducible cell therapy products, which are two features essential for partnership with Big Pharma as well as progression through the regulatory process," said Famela Ramos, Vice President of Business Development. "What we are talking about here is the production of a Third Generation Cellular Immunotherapy for cancer."

"Our Company’s philosophy has always been to leverage existing propensities of the body as opposed to fighting the body," stated Timothy Dixon, President and CEO of the Company and co-inventor. "I commend our collaborating scientists for the completely novel concept of leveraging existing premade antibodies as a new way of shutting down the formation of new blood vessels by the cancer."