On July 5, 2021 Jazz Pharmaceuticals reported that it is flying high after hitting two back-to-back regulatory milestones late last month (Press release, Jazz Pharmaceuticals, JUL 5, 2021, View Source [SID1234584747]). The first was obtaining a seven-year Orphan Drug Exclusivity for Xywav, the latest contender from its array of treatments for daytime sleepiness. Then, days later, the Dublin-based biopharma announced notching a speedy FDA approval for its blood cancer drug.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

On June 30th, Rylaze (asparaginase erwinia chrysanthemi (recombinant)-rywn) was greenlighted as a component of a chemotherapy regimen designed for treating acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LBL) in both children and adults. The drug received accelerated approval from the agency under the Real-Time Oncology Review (RTOR) program.

"We are excited to bring this important new treatment to patients who are in critical need, and we are grateful to FDA for the approval of Rylaze based on its established safety and efficacy profile. We are pleased Rylaze was approved before the trial is complete and are diligently working to advance additional clinical trial data," said Bruce Cozadd, Chairman, and CEO of Jazz Pharmaceuticals, in a statement.

"We are committed to quickly engaging with FDA to evolve the Rylaze product profile with additional dosing options and an IV route of administration."

L-Asparignase as an ALL Treatment

ALL is a rare type of blood cancer but still accounts for 30% of all cancers in children. In 1953, a discovery by Dr. John Graydon Kidd led to the widespread use of L-asparaginase as a treatment for ALL. It was found that the deprivation of the amino acid, L-asparagine, sends the leukemic cells into starvation mode, eventually killing them owing to the blockage in DNA, RNA, and protein synthesis.

Over the years, asparaginase derived from Escherichia coli was typically used as first-line therapy, but around two-thirds of patients were found to develop an allergic reaction. Such patients continued treatment with Erwinia chrysanthemi asparaginase.

Encouraging Trial Data

Rylaze is a recombinant erwinia asparaginase produced from a novel Pseudomonas fluorescens expression platform. The FDA approval was based on encouraging data from an ongoing Phase 2/3 trial that assessed the drug’s safety, tolerability, and efficacy. The study evaluated Rylaze in pediatric and adult patients with ALL or LBL who have had an allergic reaction to E. coli-derived asparaginases and have not previously received asparaginase from erwinia chrysanthemi.

Results from the first of three cohorts showed that patients who received 25 mg/m2 of Rylaze through intramuscular injection achieved intended levels of serum asparaginase activity, and nearly 94% of them maintained ≥ 0.1 U/mL of enzyme levels at 48 hours after administration.

"The accelerated development and approval of Rylaze marks an important step in bringing a meaningful new treatment option for many ALL patients – most of whom are children – who cannot tolerate E. coli-derived asparaginase medicine," said Dr. Luke Maese, Assistant Professor at the University of Utah, Primary Children’s Hospital and Huntsman Cancer Institute.

"Before the approval of Rylaze, there was a significant need for an effective asparaginase medicine that would allow patients to start and complete their prescribed treatment program with confidence in supply," he added.

Jazz reported total revenue of $2.36 Billion in 2020, of which $1,757.0 million was brought in by its combined oxybate business. Meanwhile, its total oncology net product sales accounted for $554.5 million. With the approval of some new oncology drugs, the company would be expected to exceed that number this year.

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]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

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.

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]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

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.

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.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

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.

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]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

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.