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Patrys demonstrates potential for deoxmabs in antibody drug conjugates (ADCs)

On September 15, 2021 Today Patrys reported that new data from a successful preclinical study highlighting the potential for using our deoxymab antibodies as targeting agents in antibody drug conjugates (ADCs) (Press release, Patrys, SEP 15, 2021, View Source [SID1234587728]).

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ADCs harness the targeting attributes of antibodies to deliver payloads specifically to the sites of disease, and are one of the most active areas of drug development

The study data confirms that it is possible to conjugate the anticancer drug monomethyl auristatin E (MMAE) to Patrys’ full-sized IgG deoxymab, PAT-DX3. MMAE conjugated to PAT-DX3 was shown to inhibit tumour growth by 99.7% in mice implanted with human breast cancer cells, showing that deoxymabs can be used to effectively target delivery to tumours in animals.

According to Patrys CEO and Managing Director, Dr James Campbell:

"We are very excited by the potential of using our deoxymabs as the basis for new ADCs. This work has shown that deoxymabs can be used to target cancers and, by using a potent and validated ADC payload, deliver a drug. As with the therapeutic applications we are working on, the ability of our deoxymab antibodies to target multiple types of cancer, enter the cell and cell nucleus, and transit the blood brain barrier provides some really novel ways for using them as targeting agents for ADCs.

"This study has clearly demonstrated the proof of concept and is expected to open up a range of potential development or partnering opportunities for the Company."

PsiOxus to Present Positive Biomarker Data at ESMO 2021 Demonstrating the Potential of Their Novel Tumor-Selective T SIGn® vector, NG-350A, to Re-Engineer Advanced Cancers

On September 15, 2021 PsiOxus Therapeutics, Ltd. (PsiOxus), a tumor re-engineering company, reported that they will present key safety and translational data from their first-in-human phase 1 FORTITUDE clinical study at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2021 this week. Data from the completed monotherapy dose-escalation part of the FORTITUDE study, initiated in 2019 to assess the safety and tolerability of the NG-350A T-SIGn vector, will be presented on Friday 16th September 2021, with the poster available in full at www.psioxus.com shortly afterwards.

NG-350A is a T-SIGn vector designed to re-engineer cancers by selectively expressing a CD40 agonist monoclonal antibody, a potent activator of immuno-inflammatory responses, within the tumour microenvironment. PsiOxus is developing this agent as one of several products within its T-SIGn portfolio of vectors that combine systemic delivery with localized production of powerful transgene payloads to allow the selective re-engineering of both primary and metastatic tumors.

The data to be presented at the ESMO (Free ESMO Whitepaper) Congress show that IV delivery of NG-350A results in sustained elevations of inflammatory cytokines in the phase 1 FORTITUDE trial. In particular, marked and persistent dose-dependent increases in both IL-12 and IFNγ were observed after a single 1-week course of NG-350A, indicative of robust activation of antigen presenting cells via CD40 agonism generated within the tumor. Expansion of new T cell clones, a high proportion of which were new clones, was also observed following a single cycle of NG-350A. Safety data from the 25 patients treated with NG-350A as part of the now completed monotherapy dose-escalation part of FORTITUDE demonstrated that NG‑350A was well-tolerated, with few of the adverse events associated with systemic delivery of anti-CD40 agonists observed.

Together, these data suggest NG-350A contributes to the re-programming of the tumour microenvironment while avoiding the toxicity associated with systemic non-localized dosing of anti-CD40 antibodies.

"The headline data shared at the ESMO (Free ESMO Whitepaper) Congress confirms previous findings that our T-SIGn vector replicates selectively in primary tumor cells and metastases and persists for several months after intravenous delivery. Even more importantly, the biomarker data indicates that ongoing vector replication in tumors effectively translates into sustained production of the transgene payload, in this case a CD40 agonistic antibody. This translational data is a first in class demonstration of a downstream effect of tumor re-engineering, using T-SIGn vectors to turn the patient’s tumor cells into small drug factories," said Tom Lille, M.D., Ph.D., Chief Medical Officer, PsiOxus.

Based on these highly promising data, NG-350A will be assessed in combination with an anti–PD-1 checkpoint inhibitor in Part B of FORTITUDE.

Magenta Therapeutics Announces IND Clearance for MGTA-117 Targeted Conditioning Clinical Trial

On September 15, 2021 Magenta Therapeutics, Inc. (Nasdaq: MGTA), a clinical-stage biotechnology company developing novel medicines to bring the curative power of stem cell transplant to more patients, reported that its Investigational New Drug (IND) application for MGTA-117 is active with the U.S. Food and Drug Administration (FDA) (Press release, Magenta Therapeutics, SEP 15, 2021, View Source [SID1234587726]). The company expects to open the Phase 1/2 clinical trial in Q4 2021 to evaluate its MGTA-117 antibody-drug conjugate (ADC) targeted conditioning program.

"We are very pleased that our collaboration with the FDA has resulted in the clearance of the MGTA-117 IND. We have addressed the FDA’s request for a bioassay to be incorporated into the clinical trial protocol," said Jason Gardner, D.Phil., President and Chief Executive Officer, Magenta Therapeutics. "Improving conditioning treatments is essential for broadening patient accessibility to the curative potential of stem cell transplant and gene therapies. We have designed MGTA-117 specifically to replace toxic radiation and chemotherapy-based conditioning agents used in current medical practice. This program holds significant potential for patients across several disease areas."

The multi-center, open label Phase 1/2 clinical trial with single-dose escalating cohorts will evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of MGTA-117 as a single agent in relapsed/refractory AML and MDS patients. Magenta will continue to engage with the FDA to transition the trial to the intended primary target population of hematopoietic stem cell transplant-eligible AML and MDS patients. In addition, Magenta has planned gene therapy clinical trial collaborations with AVROBIO and Beam Therapeutics to evaluate the potential utility of MGTA-117 for conditioning gene therapy patients without the use of non-selective busulfan or other toxic chemotherapies.

About MGTA-117

Magenta’s MGTA-117 program is the company’s lead targeted conditioning product candidate, an antibody-drug conjugate (ADC) designed to selectively deplete hematopoietic stem cells (HSCs) from patients prior to transplant or HSC-based gene therapy to reduce the need for high-dose or high-intensity chemotherapeutic agents or, in the case of gene therapy applications, to potentially eliminate the need for chemotherapeutic agents altogether. MGTA-117 targets the CD117 receptor, which is highly expressed on the cell surface of HSCs and leukemia cells, making it a promising target for conditioning across broad sets of diseases, including certain blood cancers, hemoglobinopathies (sickle cell disease and beta thalassemia) and inherited metabolic disorders.

Cerus Corporation to Present at the 2021 Cantor Global Virtual Healthcare Conference

On September 15, 2021 Cerus Corporation (Nasdaq: CERS) reported that William ‘Obi’ Greenman, Cerus’ president and chief executive officer, and Kevin D. Green, Cerus’ chief financial officer, are scheduled to participate in the 2021 Cantor Global Virtual Healthcare Conference on Wednesday, September 29, 2021 at 11:20 a.m. ET (Press release, Cerus, SEP 15, 2021, View Source [SID1234587725]).

A live webcast of the presentation will be available on Cerus’ Investor Relations page at View Source A replay of the webcast will be available for approximately two weeks following the completion of the event.

HOOKIPA announces clinical collaboration with Merck & Co., Inc., Kenilworth, NJ., USA to evaluate HB-200 in combination with KEYTRUDA® (pembrolizumab) in patients with advanced head and neck cancers

On September 15, 2021 HOOKIPA Pharma Inc. (NASDAQ: HOOK, ‘HOOKIPA’), a company developing a new class of immunotherapeutics based on its proprietary arenavirus platform, reported it has entered into a clinical collaboration and supply agreement with Merck & Co., Inc., Kenilworth, NJ., USA (known as MSD outside of the United States and Canada) to evaluate the combination of HB-200, a novel arenaviral immunotherapeutic, and Merck & Co., Inc., Kenilworth, NJ., USA’s anti-PD-1 therapy, KEYTRUDA (pembrolizumab) as first-line treatment for patients with advanced head and neck squamous cell carcinoma (HNSCC) (Press release, Hookipa Biotech, SEP 15, 2021, View Source [SID1234587724]).

"Our collaboration with Merck & Co., Inc., Kenilworth, NJ., USA, a proven immuno-oncology leader, is an important step as we advance our HB-200 program for the treatment of Human Papillomavirus 16-positive (HPV16+) cancers and seek to introduce a new class of immunotherapeutics," said Joern Aldag, Chief Executive Officer at HOOKIPA. "There remains considerable unmet treatment need for people with metastatic head and neck cancers, and we believe the combination of HB-200 and KEYTRUDA may offer hope. We have seen encouraging early responses in heavily pre-treated patients with the addition of KEYTRUDA in our ongoing HB-200 trial. We are excited to explore the potential benefit of HB-200 as a first-line treatment in combination with KEYTRUDA, a leading anti-PD-1 inhibitor globally, and the possibility of making a meaningful impact on patients’ lives."

The collaboration has been initiated based on promising data from the ongoing HB-200 Phase 1/2 clinical trial (NCT04180215) in advanced HPV16+ cancers. As reported at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, 15 patients with metastatic head and neck cancers were eligible for the efficacy analysis, as of data cut-off. HB-201 monotherapy showed an 18 percent overall response rate and median progression-free survival of 3.45 months in heavily pretreated head and neck cancer patients, better than current 2nd-line treatment. In addition, preliminary data on HB-201/HB-202 therapy showed a disease control rate of 100 percent (4/4 patients). Importantly, the Phase 1 data on 38 evaluable patients showed that HB-200 therapy has a favorable safety profile in heavily pre-treated patients with HPV16+ cancers, underlining its potential as a monotherapy and in possible combination with checkpoint inhibitors.

With a HB-200 program data read-out anticipated by Q4 2021, HOOKIPA anticipates initiating a Phase 2 trial with HB-200 in combination with KEYTRUDA in 2022. Additional Phase 2 expansion cohorts are also planned to start in Q1 2022.

KEYTRUDA is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

About HB-200
HB-201 and HB-202 are HOOKIPA’s lead oncology candidates engineered with the company’s proprietary replicating arenaviral vector platform. Each single-vector compound uses a different arenavirus backbone (Lymphocytic choriomeningitis virus for HB-201 and Pichinde virus for HB-202), while expressing the same antigen, an E7E6 fusion protein derived from HPV16. In pre-clinical studies, alternating administration of HB-201 and HB-202 resulted in a ten-fold increase in immune response and better disease control than either compound alone. HB-201 is being tested clinically as a single vector therapy and also in an alternating vector combination with HB-202.

About Human Papillomavirus
Human Papillomavirus, or HPV, is estimated to cause about 5 percent of the worldwide burden of cancers. This includes approximately 99 percent of cases in cervical, up to 60 percent of head and neck, 70 percent of vaginal and 88 percent of anal cancers.

The majority of these cancers are caused by the HPV serotype 16. Most infections with HPV are cleared from the body with no lasting consequences. However, in some cases, HPV DNA becomes integrated into chromosomal DNA. When host cells take up this DNA, they express the HPV E6 and E7 proteins. This uptake can potentially lead to cancer since expression of these proteins leads to alterations in cell cycle control, which in turn predisposes these cells to become cancerous.