On December 3, 2020 Antengene Corporation Limited ("Antengene", SEHK: 6996.HK), a leading innovative biopharmaceutical company dedicated to discovering, developing and commercializing global first-in-class and/or best-in class therapeutics in hematology and oncology, reported it has submitted new drug applications ("NDA(s)") for XPOVIO (selinexor, ATG-010) to the Health Sciences Authority of Singapore and to the Australian Therapeutic Goods Administration for three indications: the treatment of adult patients with relapsed or refractory multiple myeloma ("rrMM") who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody; and in combination with bortezomib and dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior line of therapy; and for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma ("rrDLBCL"), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least two lines of systemic therapy. Australian Therapeutic Goods Administration has accepted the NDA of Antengene on December 2, 2020.

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A new drug application (NDA) for XPOVIO (selinexor) has also been submitted to the Hong Kong Department of Health for the treatment of adult patients with rrMM who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody.

In South Korea, XPOVIO (selinexor) has been granted orphan drug designation for the treatment of adult patients with rrMM who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody and for the treatment of adult patients with rrDLBCL, not otherwise specified, including DLBCL arising from follicular lymphoma, after at least two lines of systemic therapy.

XPOVIO (selinexor, ATG-010) is a first-in-class and only-in-class oral selective inhibitor of nuclear export, developed by Antengene and Karyopharm Therapeutics Inc. (NASDAQ: KPTI). In July 2019, the US Food and Drug Administration (FDA) approved XPOVIO (selinexor) in combination with low-dose dexamethasone for the treatment of rrMM. After its initial approval of rrMM, FDA approved XPOVIO (selinexor) as a single-agent for the treatment of rrDLBCL in June 2020.

In November 2020, at the Connective Tissue Oncology Society 2020 Annual Meeting (CTOS 2020), Antengene’s partner, Karyopharm Therapeutics, presented positive results from the Phase 3 portion of the randomized, double blind, placebo controlled, cross-over SEAL study evaluating single agent, oral XPOVIO (selinexor) versus matching placebo in patients with liposarcoma. Karyopharm also recently announced that the ongoing phase 3 SIENDO study of XPOVIO (selinexor) in patients with endometrial cancer passed planned interim futility analysis and that Data and Safety Monitoring Board (DSMB) recommended the study should proceed as planned without any modifications. Top-line SIENDO study results are expected in the second half of 2021.

About XPOVIO

XPOVIO is a first-in-class and only-in-class oral selective inhibitor of nuclear export compound, developed by Antengene and Karyopharm Therapeutics Inc. (NASDAQ: KPTI). In July 2019, the US Food and Drug Administration (FDA) approved XPOVIO in combination with low-dose dexamethasone for the treatment of relapsed or refractory multiple myeloma (rrMM) and in June 2020 approved XPOVIO as a single-agent for the treatment of relapsed or refractory diffuse large B-cell lymphoma (rrDLBCL). XPOVIO is so far the first and only oral SINE compound approved by the FDA. XPOVIO is also being evaluated in several other mid-and later-phase clinical trials across multiple solid tumor indications, including liposarcoma and endometrial cancer.

Antengene is conducting two registrational Phase 2 clinical trials of XPOVIO in China for relapsed refractory multiple myeloma (MARCH) and for relapsed refractory diffuse large B-cell lymphoma (SEARCH), and has initiated clinical trials for high prevalence cancer types in the Asia Pacific region including peripheral T-cell lymphoma and NK/T-cell lymphoma (TOUCH) and KRAS-mutant non-small cell lung cancer (TRUMP).

On December 3, 2020 Amplyx Pharmaceuticals, a clinical-stage biopharmaceutical company developing innovative therapies for debilitating and life-threatening diseases in patients with compromised immune systems, reported that clinical and preclinical data for its Phase 2 program, MAU868, will be presented at the 62nd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition, taking place virtually on December 5-8, 2020 (Press release, Amplyx Pharmaceuticals, DEC 3, 2020, View Source [SID1234572155]).

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The ASH (Free ASH Whitepaper) abstracts are available at www.hematology.org. Details of the virtual presentations are as follows:

Title: "Preclinical Characterization of MAU868, a Novel Neutralizing Antibody Targeting BK Virus"
Abstract Number: 1475
Presenter: Atul Sathe, Novartis Institutes for BioMedical Research
Session: 721. Clinical Allogeneic Transplantation: Conditioning Regimens, Engraftment, and Acute Transplant Toxicities: Poster I
Date and Time: Saturday, December 5, 2020: Available virtually from 7:00 AM-3:30 PM PST

Title: "A First-in-Human Study of MAU868, a Novel Neutralizing Antibody Against BK Virus"
Abstract Number: 2367
Presenter: Steven J. Kovacs, Novartis Institutes for BioMedical Research
Session: 721. Clinical Allogeneic Transplantation: Conditioning Regimens, Engraftment, and Acute Transplant Toxicities: Poster II
Date and Time: Sunday, December 6, 2020: available virtually from 7:00 AM-3:30 PM PST

About MAU868
MAU868, a novel human monoclonal antibody that potently neutralizes the BK virus, which can cause significant morbidity and mortality in transplant patients. Antibodies to BKV are found in approximately 80 to 90% of adults worldwide, indicating previous infection or exposure to the virus. A weakened immune system may result in BKV reactivation and cause serious disease. In patients who have had kidney transplant, BKV can lead to the loss of the transplanted kidney. BKV reactivation in the bladder can also cause hemorrhagic cystitis. Severe cases require bladder irrigation, clot evacuation, blood transfusion, stenting and nephrostomy. There are currently no approved treatments for renal nephropathy or hemorrhagic cystitis caused by BKV.

MAU868 potently neutralizes all four major genotypes of BKV at sub-nanomolar concentrations and has a high barrier to resistance in vitro. MAU868 also has neutralizing activity against the closely related JC virus, the cause of progressive multifocal leukoencephalopathy

MAU868 is currently being evaluated in a multicenter, randomized, double-blind, placebo-controlled Phase 2 clinical trial to assess the safety, pharmacokinetics, and efficacy for the treatment of BK viremia in kidney transplant recipients at centers in the US and Canada. The study’s primary objectives are to assess the safety of MAU868 in this patient population and to evaluate the efficacy of MAU868 in reducing BKV plasma viral load.

On December 3, 2020 GEMoaB, a biopharmaceutical company focused on the development of next-generation immunotherapies for hard-to-treat cancers, reported that it has apheresed the first patient in a Phase IA study with UniCAR-T-PSMA, the lead solid tumor product candidate from its proprietary UniCAR cellular immunotherapy platform (Press release, GEMoaB, DEC 3, 2020, View Source [SID1234572154]). UniCAR-T-PSMA is investigated in late-stage, relapsed/refractory solid tumors expressing the PSMA antigen. The UniCAR platform has been designed to ensure excellent control over the universal CAR-T effector cell through a rapidly switchable on/off capability. This is combined with high flexibility to effectively target tumor antigens of choice by re-directing and activating UniCAR-T cells through soluble adapters termed Targeting Modules (TMs).

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"The unique ability to rapidly switch on and off the UniCAR-T effector cells and thereby tightly control their activity – as we have now clinically validated in our ongoing UniCAR-T-CD123 study in AML – may help to overcome many of the limitations that conventional CAR-T therapies face when targeting less differentially expressed antigens, especially in solid tumors", said Prof. Dr. Gerhard Ehninger, GEMoaB’s co-founder and Chief Medical Officer. "Our first UniCAR clinical study in solid tumors is of utmost importance for GEMoaB. We believe that the PSMA antigen is a great initial target as it is not only expressed on the tumor surface but also on the tumor neo-vasculature, allowing for a double attack of the malignant cells by UniCAR-T cells."

The Phase IA study includes patients with late-stage PSMA-positive relapsed/refractory solid tumors such as Castrate Resistant Prostate Cancer (CRPC), Non-small Cell Lung Cancer (NSCLC) or Triple Negative Breast Cancer (TNBC). It will examine the feasibility, safety and potential efficacy of the combined application of a single dose of UniCAR-T and the continuous infusion of the PSMA-specific TMpPSMA.

According to Prof. Dr. Ralf Bargou, Head of Comprehensive Cancer Center Mainfranken at the University Hospital Würzburg and coordinating investigator of this trial, the study could be an important step in the ongoing intensive research efforts to establish cellular immunotherapies as a key therapeutic pillar to improve patient outcomes in hard-to-treat solid tumor cancers. "At our National Cancer Center in Würzburg we are focusing a significant amount of our ongoing research and clinical efforts on developing breakthrough immunologic treatments of solid tumors together with our partners", said Prof. Bargou. "PSMA is a very promising target expressed in multiple late-stage cancers that do not sufficiently benefit from currently existing therapies and the UniCAR platform provides many features to finally obtain meaningful safety and efficacy results for this innovative treatment modality. We are very much looking forward working closely with the GEMoaB team on this important study."

About the UniCAR-T-PSMA Study

This first-in-human phase I study is an open-label, non-randomized, dose-finding study designed to evaluate the safety and activity of UniCAR-T-PSMA in up to 16 patients with advanced relapsed/refractory, PSMA-positive solid tumors such as CRPC, NSCLC or TNBC. Its purpose is to determine the maximum tolerated dose (MTD), dose limiting toxicities (DLT) as well as the recommended Phase II dose for the combined application of a single dose of UniCAR-T and the continuous infusion of TMpPSMA over 25 days. The study will also investigate response rates, persistence of UniCAR-T cells over time as well as the ability to rapidly switch UniCAR-T cells on and off in case of side effects through stopping the TM infusion. The study will take place at selected Phase I and CAR-T experienced University centers in Germany. It is supported by a grant from the European Regional Development Fund (ERDF) provided through Saxony’s Development Bank (SAB). To learn more about the trial, please visit clinicaltrials.gov.

About UniCAR

GEMoaB is developing a rapidly switchable universal CAR-T platform, UniCAR, to improve the therapeutic window and increase efficacy and safety of CAR-T cell therapies in challenging cancers, including acute leukemias and solid tumors. Conventional CAR-T cells depend on the presence and direct binding of cancer antigens for activation and proliferation. An inherent key feature of the UniCAR platform is a rapidly switchable on/off mechanism (less than 4 hours after interruption of TM supply) enabled by the short pharmacokinetic half-life and fast internalization of soluble adaptors termed TMs. These TMs provide the antigen-specificity to activate UniCAR gene-modified T-cells (UniCAR-T) and consist of a highly flexible antigen binding moiety, linked to a small peptide motif recognized by UniCAR-T.

On December 3, 2020 F-star Therapeutics, Inc. (NASDAQ: FSTX), a clinical-stage biopharmaceutical company dedicated to developing next generation immunotherapies to transform the lives of patients with cancer, reported that the first patient has been dosed in its Phase 1 trial evaluating FS120, a first-in-class dual-agonist tetravalent bispecific antibody targeting CD137 (4-1BB, TNFRSF9) and OX40 (CD134, TNFRSF4) (Press release, F-star, DEC 3, 2020, View Source [SID1234572153]).

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The adaptive Phase 1 trial will explore FS120 as a monotherapy in dose escalation including evaluation of PK/PD in patients with advanced cancer. FS120 will also be evaluated in combination with a PD-1 monoclonal antibody with the potential for early demonstration of efficacy in specific tumor subtypes.

FS120 has the potential to show activity in "cold" tumors and improve outcomes of existing immunotherapies by simultaneously agonizing CD137 and OX40. These two receptors are part of the Tumor Necrosis Factor Receptor family ("TNFRSF") and are widely expressed on activated T cells and NK cells in tumors. Many TNFRSF-targeting antibodies require crosslinking via Fcγ receptors ("FcγRs") to show activity, but this engagement can limit their clinical activity and lead to significant toxicity. FS120 has been designed to be FcγR-null and instead uses bispecific crosslinking to drive robust receptor clustering and activation, without engaging the FcγR. FS120 preclinical data demonstrated delays in tumor growth, activation and proliferation of CD4+ and CD8+ T cells, and synergies with PD-1 monoclonal antibodies and chemotherapies.

Louis Kayitalire, CMO of F-star, said: "The initiation of this trial is a significant milestone for F-star as we look to transform the care of those patients with cancer who have limited treatment options. FS120 offers an opportunity to improve upon current treatment paradigms, either as a monotherapy or in combination. We look forward to the results from our FS120 clinical trial as we strive to improve both quality of life and duration of response for patients with these difficult to treat cancers."

On December 3, 2020 Sirnaomics, Inc., a biopharmaceutical company engaged in the discovery and development of RNAi therapeutics against cancer and fibrotic diseases, reported that the company has received feedback from the U.S. Food and Drug Administration (FDA) and may now proceed with a planned Phase I clinical study of its leading drug candidate, STP705, for treatment of multiple types of liver cancer (Press release, Sirnaomics, DEC 3, 2020, View Source [SID1234572152]).

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The FDA has provided valuable feedback on the company’s proposed trial design for a "Phase 1 Multicenter, Open-Label, Dose Escalation Study and Dose Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Anti-Tumor Activity of STP705 Administered Intratumorally in Cholangiocarcinoma, Hepatocellular Carcinoma or Liver Metastases in Subjects With Advanced / Metastatic or Surgically Unresectable Solid Tumors Who Are Refractory to Standard Therapy." The first patient is expected to be enrolled in the study in the first quarter of 2021. STP705 is a small interfering RNA (siRNA) therapeutic that utilizes a proprietary polypeptide nanoparticle (PNP)-enhanced delivery system to inhibit expression of TGF-β1 and COX-2 in targeted tissue and cells. Preclinical animal models have demonstrated its effective anti-tumor activity for treatments of cholangiocarcinoma and hepatocellular carcinoma.

"Receiving the required feedback from the FDA now permits us to proceed with this Phase I study that represents an important step forward in demonstrating the broader clinical utility of our siRNA therapeutic candidates," said Patrick Y. Lu, PhD, Sirnaomics’ Founder and CEO. "Liver cancer treatment remains a critical unmet need globally and especially in Asian countries. Our clinical strategy leveraging STP705’s FDA Orphan Drug designation for the treatment of cholangiocarcinoma and hepatocellular carcinoma will potentially be highly beneficial to patients suffering these life threatening diseases in both the US and Asia. We are anticipating that this clinical study will contribute to the expanding clinical evidence supporting extensive therapeutic potential of STP705 against various cancers."

"Liver cancer continues to be a devastating disease for patients with high mortality and high unmet medical need," stated Michael Molyneaux, MD, Sirnaomics’ Chief Medical Officer. "This disease fits with Sirnaomics mission to bring lifesaving drugs to patients with severe debilitating medical illness. We hope to gain important insight into the potential safety and efficacy of STP705 in this Phase I trial and we expect to build on the data from this study to expand into other oncology indications."

About Liver Cancer

Liver cancer is a global health problem, with liver neoplasms representing the second-most frequent cause of cancer-related death. There are many different types of liver cancers including hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), liver angiosarcoma, hepatoblastoma and others. Additionally, liver is a highly metastasis-permissive organ. It is the most frequently afflicted organ by metastasis and liver metastases are much more common than primary hepatic tumors. The distinctive biology of the liver renders it intrinsically susceptible to metastases. The true prevalence of liver metastasis is unknown, but between 30% and 70% of patients dying of cancer have liver metastases and most patients with liver metastases will die of their disease.

STP705 and Liver Cancer

Over expressions of TGF-β1 and COX-2 have been well-characterized as playing key regulatory roles in tumorigenesis. TGF-β is produced by different liver cells and is demonstrated to induce tumor cell migration and survival. TGF-β has been found to be overexpressed in metastatic HCC tissues. Overexpression of TGF-β is generally accepted to be associated with metastasis and poor prognosis. COX-2 is reported to be highly expressed in cancer stem cells and promotes cell migration in HCC cell lines. Additionally, inhibition of COX-2 suppresses cell migration and induces apoptosis. As such TGF-β1 and COX-2 are excellent therapeutic targets for treatment of liver cancer.

STP705 is composed of two siRNA oligonucleotides targeting TGF-β1 and COX-2 mRNA respectively and formulated in nanoparticles with a proprietary Histidine-Lysine Co-Polymer (HKP) peptide. Each individual siRNA has demonstrated the ability to inhibit the expression of their target mRNA and combining the two siRNAs produces a synergistic effect that diminishes pro-fibrogenic, pro-inflammatory, and pro-tumorigenic factors. Sirnaomics has completed numerous pre-clinical studies that demonstrate that inhibition of TGF-β1 and COX-2 is expected to result in the inhibition of tumor growth and provide an alternative approach for the treatment of various liver cancers. Molecular analyses of the effects of administering the combination demonstrated that the inhibition of these targets had effects on downstream gene products associated with numerous oncology targets. Additional immunohistochemistry and image analyses of the liver and tumor tissues demonstrated that animals treated with STP705 resulted in increased CD4+ and CD8+ T cell infiltration within the tumor microenvironment. Using STP705 for treatments of hepatocellular carcinoma and cholangiocarcinoma have been designated as Orphan Drug indications by U.S. FDA. STP705 has also been evaluated in a Phase IIa clinical trial for treatment of Non-melanoma skin cancer.