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Imugene Announces Presentation for Lead HER-2 Cancer Immunotherapy at the ESMO
World Congress on Gastrointestinal Cancer 2021 Annual Meeting

On July 5, 2021 Imugene Limited (ASX:IMU), a clinical stage immuno-oncology company, reported the company presented on the HER-Vaxx cancer immunotherapy program at the ESMO (Free ESMO Whitepaper) World Congress on Gastrointestinal Cancer 2021 Annual Meeting (Press release, Imugene, JUL 5, 2021, View Source [SID1234584745]).

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The abstract presentation was entitled ‘HERIZON: A PHASE 1B/2 OPEN-LABEL STUDY OF IMU-131 HER2/NEU PEPTIDE VACCINE PLUS STANDARD OF CARE CHEMOTHERAPY WITH RANDOMIZATION IN PHASE 2 IN PATIENTS WITH HER2/NEU OVEREXPRESSING METASTATIC OR ADVANCED ADENOCARCINOMA OF THE STOMACH OR GASTROESOPHAGEAL JUNCTION’ Updated Interim Analysis Results.

The presentation expanded on previously presented interim analysis data presented at AACR (Free AACR Whitepaper)2021.

To recap previously released results:
• Interim analysis in the randomized Phase 2 study showed statistically significant overall survival Hazard Ratio (HR) of 0.418 (80% 2-sided CI: 0.186, 0.942); HER-Vaxx showed a reduced risk of death of 58.2% in the HER-Vaxx plus chemotherapy group as compared to chemotherapy alone.
• The median overall survival (OS) for patients receiving HER-Vaxx plus chemotherapy was 14.2 months, compared to 8.8 months in patients treated with chemotherapy alone.
• The Phase 2 data represent a clinical proof-of-concept signal for HER-Vaxx when added to chemotherapy and indicate that B-cell activating immunotherapy vaccines can induce clinically active antibody responses.
• Recruitment of the Phase 2 trial was completed in January 2021.

The ESMO (Free ESMO Whitepaper) presentation highlights and presents the following new data:
• HER-Vaxx treatment resulted in a 50% Overall Response Rate (ORR) compared to 29% in patients treated with chemotherapy alone. The ORR measures the percentage of patients who responded to treatment with a partial response (PR) or better. 2 IMUGENE LIMITED ACN 009 179 551
• Treatment with HER-Vaxx clearly demonstrates patients develop high levels of HER2-specific antibodies early in the treatment protocol and are maintained during treatment and maintenance phase with only a few booster injections.
• Tumour response is correlated with the amount of antibody levels. Patients with antibody levels higher than 1050ng/ml received greater than 50% tumour reduction and may serve as a potential biomarker.
• In contrast to patients on chemotherapy alone, the reduction of tumour size is substantially higher in patients that received HER-Vaxx + chemotherapy.

Overall, this data demonstrates HER-Vaxx may provide treatment benefits consistent with traditional monoclonal antibodies with a corresponding adaptive immune response without added toxicity.

Imugene’s HER-Vaxx is a B-cell activating cancer immunotherapy designed to treat tumours that overexpress the HER-2/neu receptor, such as gastric, breast, ovarian, lung and pancreatic cancers. The immunotherapy is constructed from several B cell epitopes derived from the extracellular domain of HER2/neu. It has been shown in pre-clinical studies and in Phase 1 and 2 studies to stimulate a potent polyclonal antibody response to HER-2/neu, a well-known and validated cancer target.

Positive results from immunogenicity testing send Prescient’s shares higher

On July 5, 2021 Prescient Therapeutics Limited (ASX:PTX) reported that outstanding findings from in silico immunogenicity testing of OmniCAR’s key binding components – SpyTag and SpyCatcher (Press release, Prescient Therapeutics, JUL 5, 2021, View Source;utm_medium=rss&utm_campaign=positive-results-from-immunogenicity-testing-send-prescients-shares-higher [SID1234584687]).

SpyTag/SpyCatcher system is a technology used to combine proteins; SpyTag is a 13-amino acid peptide which reacts with SpyCatcher to form a bond.

Following the significant update, shares of the ASX-listed clinical-stage oncology firm jumped 14.130% and were trading at AU$0.260 (at 02:48 PM AEST).

PTX highlighted that the in silico tests confirm the non-immunogenic profile of SpyTag and SpyCatcher. These findings substantially de-risk the OmniCAR platform and are crucial for progressing Prescient’s OmniCAR in-house programs and external partnership/collaborations.

Immunogenicity testing assesses the immune response against a new treatment, which can negatively affect efficacy and safety. In CAR-T cell therapies, elevated levels of immunogenicity can negatively impact the expansion and persistence of CAR-T cells, affecting the treatment’s overall safety and clinical response.

WATCH NOW: Expert Talks With Mr Steven Yatomi Clarke, CEO and Managing Director of Prescient Therapeutics

In silico test demonstrates low immunogenicity of SpyTag and SpyCatcher
Prescient highlighted that the immunogenicity of OmniCAR’s binding system components – SpyTag and SpyCatcher – were analysed in silico by an independent US research provider. The study was performed to determine if these components could generate unfavourable immune responses which could have a negative impact on the therapy.

Source: PTX Update, 5 July 2021

The findings revealed that both SpyTag and SpyCatcher had extremely low immunogenicity. Notably, their immunogenicity was found to be lower than a panel of humanised therapeutic antibodies already approved for human use.

ALSO READ: Prescient Therapeutics’ major strides in anti-cancer programs set the stage for a sturdy 2021

It is interesting to note that in silico immunogenicity testing is widely considered to be over-predictive as contemporary algorithms cannot account for cellular antigen processing.

Steven Yatomi-Clarke, the CEO and Managing Director of Prescient, commented-

The crucial development follows the completion of the manufacturing and delivery of the OmniCAR platform’s critical components, including cell binders for numerous cancer targets and lentiviral vectors utilised to manufacture CAR-T cells.

READ MORE: Prescient Therapeutics reaches a major CAR-T manufacturing milestone

Prescient’s OmniCAR programs are being developed for:

Acute myeloid leukemia (AML).
Her2+ solid tumours (breast, gastric and ovarian cancers).
Glioblastoma multiforme or GBM (the most common form of brain cancer).
PTX has developed OmniCAR as a platform, allowing collaborations and partnerships under licence with third parties wanting to integrate OmniCAR for enhancing their respective cell therapies.

The platform is based on technologies developed at the University of Pennsylvania and the University of Oxford. Interestingly, Prescient owns a global licence for the commercialisation of the technologies.

DO READ: Prescient Therapeutics inks new deal with Peter Mac to rev up its OmniCAR programs

Prescient highlights that the positive findings from the in silico immunogenicity test show that if these therapies are given to patients, their immune systems will not impair the therapy itself. Furthermore, the Company is thrilled to progress its in-house next-generation cell therapies for cancer treatments.

Prescient achieves key milestone by demonstrating OmniCAR’s key components show minimal immunogenicity in silico

On July 5, 2021 Prescient Therapeutics Limited (ASX: PTX), the clinical stage oncology company developing personalised medicine approaches to cancer, reported excellent results from in silico immunogenicity testing of OmniCAR’s key binding components, SpyTag and SpyCatcher (Press release, Prescient Therapeutics, JUL 5, 2021, file:///C:/Users/komal/Downloads/PTX_PTX_successful_immunogenicity_testing_of_OmniCAR%20(1).pdf [SID1234584601]). These results substantially de-risk the entire platform and are important for progressing Prescient’s in-house programs and external collaborations with OmniCAR.

Immunogenicity testing evaluates the immune response against a new therapy, which can adversely affect safety and efficacy. In the case of CAR-T cell therapies, high levels of immunogenicity can adversely impact CAR-T cell expansion and persistence, which can impact the overall safety and clinical response of the treatment.1

The immunogenicity of OmniCAR’s binding system components – SpyTag and SpyCatcher were tested in silico by an independent US research provider to determine if either component has the potential to elicit unfavourable immune responses that could compromise the therapy.

The results demonstrated that both SpyTag and SpyCatcher have very low immunogenicity-lower than a panel of humanised therapeutic antibodies already approved for human use and on par with circulating human antibodies. It is worth noting that in silico immunogenicity testing is widely recognised as being over-predictive as contemporary algorithms are unable to account for cellular antigen processing. 1 Gorovits B, Koren E. Immunogenicity of Chimeric Antigen Receptor T-Cell Therapeutics. BioDrugs. 2019 Jun;33(3):275-284. Figure 1: SpyCatcher and SpyTag linked to either a heavy (H) or light (L) chain human IgG, were of either lower or comparable immunogenicity when compared against human monoclonal antibodies approved for human use, and have comparable to immunogenicity to human antibodies.

Prescient’s CEO and Managing Director, Steven Yatomi-Clarke said, "This is another incremental but important milestone that significantly de-risks the entire OmniCAR platform. The immunogenicity results could not have been better. 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. This is essential not only for Prescient’s three in-house OmniCAR programs, but also for potential external collaborators, who consider immunogenicity very stringently."

"Prescient’s development plan is on schedule to deliver a number of important milestones. Together with our talented research team at Peter Mac, we are excited to progress our inhouse next generation cell therapies for cancer patients." The development follows the successful completion of manufacturing and delivery of critical components of the OmniCAR platform including cell binders for several cancer targets and lentiviral vectors used to produce CAR-T cells.

Prescient is developing OmniCAR programs for acute myeloid leukemia; Her2+ solid tumours, including breast, ovarian and gastric cancers; and glioblastoma multiforme (the most common form of brain cancer). In addition, Prescient has developed OmniCAR as a platform, allowing collaborations and partnerships under licence with third parties wishing to incorporate OmniCAR to enhance their respective cell therapies.

The OmniCAR platform is based on technologies developed at the University of Pennsylvania and University of Oxford. Prescient has a worldwide licence to commercialise the technologies.

Everest Medicines Announces that Spero Therapeutics Entered into Licensing Agreement with Pfizer Inc. for SPR206 in ex-U.S. and ex-Asia Territories

On July 5, 2021 Everest Medicines (HKEX 1952.HK), a biopharmaceutical company focused on developing and commercializing transformative pharmaceutical products for patients in Greater China and other parts of Asia, reported that Spero Therapeutics, Inc. (Nasdaq: SPRO), a licensing partner of Everest Medicines, entered into a regional licensing agreement with Pfizer Inc. (NYSE: PFE) for SPR206, Spero’s intravenously (IV)-administered next-generation polymyxin product candidate being developed to treat serious multi-drug resistant (MDR) Gram-negative infections in the hospital setting (Press release, Everest Medicines, JUL 5, 2021, View Source [SID1234584598]).

Under the terms of the licensing agreement, Spero has granted Pfizer the rights to develop, manufacture, and commercialize SPR206 in ex-U.S. and ex-Asia territories. In exchange for these rights, Spero is eligible to receive up to $80 million in development and sales milestones, and high single digit to low double-digit royalties on net sales of SPR206 in these territories. Pfizer has also made a $40 million equity investment in Spero as part of the Pfizer Breakthrough Growth Initiative, a program focused on funding innovative science to meet patient needs.

Under a licensing agreement with Spero that was announced in January of 2019, Everest Medicines has exclusive rights to develop, manufacture and commercialize SPR206 in Greater China, South Korea and certain Southeast Asian countries (the "Territory") for the treatment of multi-drug resistant (MDR) Gram-negative bacterial infections. The licensing agreement was amended in January 2021 for the assignment of relevant patents for SPR206 in the Territory to Everest. This license agreement between Spero and Pfizer will have no impact on Everest’s rights for SPR206.

"This deal reinforces the potential for SPR206 to serve as an innovative treatment option for MDR Gram-negative bacterial infections, which is a critical ongoing global public health issue," said Kerry Blanchard, MD, PhD, CEO of Everest Medicines. "Pfizer is a leader in the anti-infective therapeutic space, and Pfizer’s decision to partner with Spero on this important asset is a testament to Everest’s strategic approach to choosing promising and valuable development-stage global assets. We look forward to contributing to the broad and rapid clinical development of SPR206 as we work to address the challenges of MDR Gram-negative bacterial infections."

About SPR206

SPR206 is a potentially best-in-class, novel polymyxin derivative that was designed to reduce the kidney toxicity that is seen clinically with polymyxin B and colistin. Polymyxins are antibiotics frequently used as a last resort for challenging MDR gram-negative infections, but they are associated with significant neurotoxicity and nephrotoxicity. In a double-blind, placebo-controlled Phase 1 clinical trial in healthy volunteers conducted by our partner Spero Therapeutics, SPR206 appeared well tolerated at doses likely to be within a therapeutic range for MDR Gram-negative bacterial infections. Importantly, it also showed no evidence of nephrotoxicity at the doses tested.

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]).

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).