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Antengene Announces Acceptance of IND Application in China for the Phase II Clinical Trial of Single-Agent Selinexor for the Treatment of Myelofibrosis (MF)

On July 5, 2021 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 that China’s National Medical Products Administration (NMPA) has accepted the Investigational New Drug (IND) application for single agent selinexor, a first-in-class orally available Exportin 1 (XPO1) inhibitor, for the treatment of patients with myelofibrosis (MF) in China (Press release, Antengene, JUL 5, 2021, View Source [SID1234584597]).

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MF is a clonal hematologic neoplasm which can emerge either as primary MF, polycythemia vera (PV) or essential thrombocythemia (ET)[1]. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is currently the only curative treatment for MF. However, such treatment is difficult to carry out and has a low rate of success. According to the National Comprehensive Cancer Network (NCCN) Guidelines for the Treatment of MF, patients with intermediate-2 or high-risk MF ineligible for allo-HSCT and with a platelet count of ≥50×109/L should be treated with ruxolitinib or fedratinib, while there are few follow-on treatment alternatives for patients failed or resistant to ruxolitinib. At present, only ruxolitinib has been approved for clinical treatment in China, and as a result, MF remains a disease with limited treatment options, representing an urgent unmet medical need.

This randomized, open-label, multicenter Phase II study is designed to evaluate the safety and efficacy of selinexor versus physician’s choice (PC) in patients with MF who had at least six months of treatment with a JAK1/2 inhibitor. Approximately 112 patients with MF from 75 trial centers across the world will be randomized in a 1:1 ratio into one of the two treatment arms.

"This acceptance by the NMPA of the IND application for the China study of selinexor in patients with MF marks another major step forward in our effort to develop selinexor into a novel cancer drug. It also paves the way for our on-going exploration of additional indications for Antengene’s novel assets," said Dr. Jay Mei, Founder, Chairman and CEO of Antengene. "We are hopeful that, through this novel drug candidate with strong potential in this disease, coupled with our deep expertise in the field of hematologic malignancies, we will be able to bring renewed hope to patients with MF in China. Moving forward, we will work closely with the NMPA to advance this trial in China, and strive to bring this innovative therapeutic to patients in the region and beyond."

About Selinexor (XPOVIO)

Selinexor is a first-in-class oral selective inhibitor of nuclear export (SINE) compound discovered and developed by Karyopharm Therapeutics Inc. (NASDAQ: KPTI), Selinexor is currently being developed by Antengene, which has the exclusive development and commercial rights in certain Asia-Pacific markets, including Greater China, South Korea, Australia, New Zealand and the ASEAN countries.

In July 2019, the US Food and Drug Administration (FDA) approved selinexor in combination with low-dose dexamethasone for the treatment of relapsed/refractory multiple myeloma (RRMM) and in June 2020 approved selinexor as a single-agent for the treatment of relapsed/refractory diffuse large B-cell lymphoma (RR DLBCL). In December 2020, selinexor also received FDA approval as a combination treatment for multiple myeloma after at least one prior therapy. In February 2021, selinexor was approved by the Israeli Ministry of Health for the treatment of patients with RRMM or RR DLBCL and in March 2021, the European Commission (EC) has granted conditional marketing authorization for selinexor (NEXPOVIO) for the treatment of adult patients with RRMM.

Selinexor is so far the first and only oral SINE compound approved by the FDA and is the first drug approved for the treatment of both MM and DLBCL. Selinexor is also being evaluated in several other mid-and later-phase clinical trials across multiple solid tumor indications, including liposarcoma and endometrial cancer. In November 2020, at the Connective Tissue Oncology Society 2020 Annual Meeting (CTOS 2020), Antengene’s partner, Karyopharm, presented positive results from the Phase III randomized, double blind, placebo controlled, cross-over SEAL trial evaluating single agent, oral selinexor versus matching placebo in patients with liposarcoma. Karyopharm also announced that the ongoing Phase III SIENDO trial of selinexor in patients with endometrial cancer passed the planned interim futility analysis and the Data and Safety Monitoring Board (DSMB) recommended the trial should proceed as planned without any modifications. Top-line SIENDO trial results are expected in the second half of 2021.

Antengene is currently conducting five late-stage clinical trials of selinexor for the treatment of MM, DLBCL, non-small cell lung cancer, and peripheral T and NK/T-cell lymphoma. Furthermore, Antengene has submitted New Drug Applications (NDAs) for selinexor in multiple Asia-Pacific markets including China, Australia, South Korea, and Singapore, and was granted the Priority Review status by China’s NMPA and an Orphan Drug Designation by the Ministry of Food and Drug Safety of South Korea (MFDS).

Innovent and Laekna Therapeutics Enter a Partnership Agreement to Co-Develop Combination Therapy of Sintilimab and Afuresertib in Clinical Studies in China

On July 5, 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 Laekna Therapeutics Shanghai Co., Ltd. (Laekna), an emerging innovative pharma company based in China’s "Zhangjiang Pharma Valley" and New Jersey in the U.S., focusing on developing new ground-breaking innovative therapies to treat cancer and liver diseases, reported they have entered into a collaboration agreement to evaluate the combination of Innovent’s PD-1 inhibitor sintilimab and Laekna’s pan-AKT kinase inhibitor afuresertib (Press release, Innovent Biologics, JUL 5, 2021, View Source;agreement-to-co-develop-combination-therapy-of-sintilimab-and-afuresertib-in-clinical-studies-in-china-301325531.html [SID1234584596]).

Under the agreement, the two companies will work together to conduct clinical studies assessing the combination of sintilimab and afuresertib (LAE002) in patients with multiple types of solid tumors that have been refractory – or failed to respond – to treatment with PD-1/PD-L1 inhibitors. The trials will evaluate the safety, pharmacokinetics, pharmacodynamics and preliminary efficacy of the combination therapy. An investigational new drug (IND) application will soon be filed with the National Medical Products Administration (NMPA) in China.

Dr. Hui Zhou, Senior Vice President of Clinical Development of Innovent, said, "Since our inception in 2011, Innovent has built a robust pipeline of assets with five innovative drugs approved for marketing. Many unmet medical needs still exist for cancer patients around the world. To help address this, Innovent explores multiple indications and combinations of therapies when developing its existing and new drug candidates. At the same time, we seek to work together with additional collaborative partners as the Chinese biopharmaceutical industry continues to rapidly expand. Innovent is impressed with Laekna’s R&D pipeline and research team, and we look forward to our close collaboration and future possibilities produced by this clinical development agreement."

Dr. Yue Yong, Chief Medical Officer of Laekna, stated, "We hope our leading pipeline candidate afuresertib can potentially become a first-in-class targeted treatment in multiple types of cancer by demonstrating improved efficacy and acceptable safety in clinical trials. Notably, sintilimab was included in China’s National Reimbursement Drug List (NRDL) in 2019 as the first PD-1 inhibitor and the only PD-1 inhibitor to be included in the list that year. In addition, sintilimab, in combination with pemetrexed and platinum chemotherapy, is currently being reviewed by the U.S. FDA for a potential BLA approval in the first-line treatment of nonsquamous non-small cell lung cancer. We now have the opportunity to explore the combination therapy of afuresertib and sintilimab in multiple types of solid tumors, with a particular focus on cancers that have commonly shown to be refractory to treatment with PD-1/PD-L1 inhibitors. We hope this combination therapy demonstrates results that can ultimately lead to it becoming a new treatment option for people with these difficult-to-treat cancers."

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 Eli Lilly and Company. Sintilimab is an 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 four 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
In combination with BYVASDA (bevacizumab biosimilar injection) for the first-line treatment of hepatocellular carcinoma
Additionally, Innovent currently has a regulatory submission under review in China for sintilimab for the second-line treatment of squamous non-small cell lung cancer.

Innovent also has two clinical studies of sintilimab that have met their primary endpoints:

In combination with cisplatin plus paclitaxel or cisplatin plus 5-fluorouracil for the first-line treatment of esophageal squamous cell carcinoma
The second-line treatment of esophageal squamous cell carcinoma
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.

About Afuresertib (LAE002)

Afuresertib (LAE002) is an oral, small molecule pan-AKT kinase inhibitor. It has been investigated in over 10 Phase 1/2 clinical trials, including ovarian cancer, gastric cancer, multiple myeloma, and melanoma. These studies have demonstrated that afuresertib has strong anti-cancer activities and a tolerable safety profile in these studies.

In recent years, AKT (a serine/threonine-protein kinase) has emerged as an important mechanism in oncology, as it plays an important role in regulating various cell functions such as metabolism, survival, proliferation, tissue invasion, and chemotherapy resistance. PTEN deletion and AKT/PIK3CA alteration may lead to excessive activation of the AKT signaling pathways, which is one of the key drivers for cancer growth. The increased activation of the AKT signaling pathway is particularly common in recurrent ovarian cancer, breast cancer, and prostate cancer.

The global randomized, open-label, multi-center Phase 2 PROFECTA-II clinical trial of afuresertib is the world’s first registration-directed clinical study of a pan-AKT kinase inhibitor to treat platinum-resistant ovarian cancer. Laekna currently expects primary results of the endpoints will be available in 2022 and will discuss the data with regulatory authorities if the study outcome supports it.

Allarity Therapeutics Receives Acceptance & Review Notification from U.S. FDA for Pre-Market Approval Application for Dovitinib-DRP®

On July 5, 2021 Allarity Therapeutics A/S ("Allarity" or the "Company") reported that the U.S. Food and Drug Administration (FDA) has provided a positive administrative acceptance and review notification for the Company’s PMA application for its Dovitinib-DRP, the Company’s validated companion diagnostic for the drug dovitinib (Press release, Allarity Therapeutics, JUL 5, 2021, View Source [SID1234584595]). Dovitinib is a small molecule, pan-tyrosine kinase inhibitor in-licensed from Novartis, and is Allarity’s most advanced clinical asset.

On 2 April, 2021, Allarity announced the filing of the PMA application. The FDA’s acceptance of the Company’s PMA application means that the FDA has made a threshold determination that the application is sufficiently complete to begin an in-depth review. Allarity’s PMA application, to gain FDA approval to use the Dovitinib-DRP as a companion diagnostic to select and treat patients likely to respond to dovitinib, supports the Company’s imminent NDA filing for the drug, and is the Company’s first PMA filing for a drug-specific DRP companion diagnostic.

Allarity’s CEO, Steve Carchedi, noted, "The FDA’s acceptance of our PMA filing for the Dovitinib-DRP companion diagnostic is an important milestone for our Company. This marks a turning point for our DRP technology, as it represents the first time in our Company’s history that we have advanced towards regulatory approval for one of our drug-specific DRP companion diagnostics."

Allarity’s unique and clinically validated DRP biomarker technology makes it possible to predict whether a particular cancer patient is likely to benefit from treatment with dovitinib, in addition to a broad range of anti-cancer drugs. DRP drug response assessments for individual patients are done based on a biopsy from the patients’ tumor. The Dovitinib-DRP companion diagnostic is intended to be used to identify patients suffering from renal cell carcinoma (RCC) who by the gene expression signature of their tumor are found to have a high likelihood of responding to dovitinib.

Allarity plans to file an NDA with the FDA for the approval of dovitinib for the treatment of renal cell carcinoma (kidney cancer) during 2021. If the FDA, following the agency’s complete review process, provides the anticipated PMA approval of the Dovitinib-DRP as a companion diagnostic for dovitinib, as well as an NDA approval for dovitinib, Allarity will be able to market dovitinib in the U.S. to DRP-selected RCC patients as an effective new therapy to treat their disease.

Scandion Oncology announces that its President & CEO has bought 10,800 shares in Scandion Oncology

On July 5, 2021 Scandion Oncology A/S ("Scandion Oncology") reported that its President & CEO, Bo Rode Hansen, has bought additional 10,800 shares in Scandion Oncology resulting in a total holding on 35,900 shares in the Company (Press release, Scandion Oncology, JUL 5, 2021, View Source;ceo-has-bought-10-800-shares-in-scandion-oncology,c3380226 [SID1234584594]).

Prescient shares rip higher as immunogenicity testing results for OmniCAR ‘could not have been better’

On July 5, 2021 Prescient Therapeutics reported The results significantly de-risk the project as PTX continues development of its OmniCAR platform (Press release, Prescient Therapeutics, JUL 5, 2021, View Source;utm_medium=rss&utm_campaign=prescient-shares-rip-higher-as-immunogenicity-testing-results-for-omnicar-could-not-have-been-better [SID1234584593]).

As it builds out its OmniCAR cancer treatment platform, clinical stage oncology company Prescient Therapeutics (ASX:PTX) has updated investors with a run of positive news flow in recent weeks.

And that run continued this morning as PTX announced strong results upon completion of its in silico (computer simulated) immunogenicity testing program.

The testing program was carried out on SpyTag and SpyCatcher – Prescient’s two proprietary components that bind cancer-fighting T-cells with a targeting ligand in order to target specific proteins.

Results "could not have been better"
Investors responded to the update, sending shares in PTX more than 13 per cent higher in morning trade to 26c.

"Immunogenicity testing evaluates the body’s immune response against a new therapy, which can adversely affect safety and efficacy", PTX explained.

In that context, the immunogenicity results for SpyTag and SpyCatcher "could not have been better", CEO Steven Yatomi-Clarke said.

The immunogenicity levels were "lower than a panel of humanised therapeutic antibodies already approved for human use", an equivalent to existing antibodies produced naturally by the human body.

"In short, it gives us confidence that if these therapies are ultimately delivered to patients, that their immune systems will not impair the therapy itself," Yatomi-Clarke said.

That marks a key step forward not only for the development of Prescient’s three in-house OmniCAR programs, but also for potential partners and collaborators that want to licence the OmniCAR platform.

"These results substantially de-risk the entire platform and are important for progressing Prescient’s in-house programs and external collaborations with OmniCAR," Prescient said.

The immunogenicity results follow on from a key manufacturing milestone last month, when Prescient announced production was complete for a range of binders that target multiple cancers.

And today’s update confirms the PTX management team continues to execute on both its in-house CAR-T treatment and the OmniCAR licensing platform.

The company is developing OmniCAR programs for the treatment of myeloid leukemia; Her2+ solid tumours (including breast, ovarian and gastric cancers), and glioblastoma multiforme (the most common form of brain cancer).

Development remains ongoing at the world-leading Peter MacCallum cancer research centre in Melbourne.

This article was developed in collaboration with Prescient Therapeutics, a Stockhead advertiser at the time of publishing.

This article does not constitute financial product advice. You should consider obtaining independent advice before making any financial decisions.