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Ascendis Pharma A/S Presents New Non-Clinical Data for TransCon™ TLR7/8 Agonist Oncology Program at SITC 2021

On November 9, 2021 Ascendis Pharma A/S (Nasdaq: ASND) reported two poster presentations featuring new non-clinical data for its investigational TransCon TLR7/8 Agonist product candidate at SITC (Free SITC Whitepaper) 2021, the annual meeting for the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) taking place virtually and in person November 10-14 in Washington, D.C (Press release, Ascendis Pharma, NOV 9, 2021, View Source [SID1234594857]).

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The data show that, as designed, TransCon TLR7/8 Agonist, which leverages the Company’s innovative TransCon hydrogel technology, provides sustained activation of both innate and adaptive immune mechanisms with low systemic cytokine levels.

The posters being presented at SITC (Free SITC Whitepaper) 2021 are:

Poster #769
Friday,
November 12 A Single Dose of Intratumoral TransCon TLR7/8 Agonist Monotherapy Promoted Sustained Activation of Antigen Presenting Cells Resulting in CD4+ and CD8+
T Cell Activation and Tumor Growth Inhibition
Poster #16
Saturday,
November 13
Tumor Growth Inhibition Mediated by a Single Dose of Intratumoral TransCon TLR7/8 Agonist Associated with Activated Circulating T and B cells and Sustained Low Levels of Systemic Cytokines

"We are designing TransCon TLR7/8 Agonist for sustained and controlled release of resiquimod, a potent TLR7/8 agonist, with the goal of maximizing therapeutic benefit and addressing the known limitations of current approaches, including serious systemic toxicity and rapid effusion from the tumor," said Juha Punnonen, Ascendis Pharma’s Senior Vice President and Head of Oncology. "We are incredibly pleased to confirm with these non-clinical studies that a single intratumoral injection of sustained release unmodified resiquimod delivered through our unique hydrogel technology worked in the expected way. We look forward to sharing initial data from our Phase 1/2 clinical trial soon."

About TransCon TLR7/8 Agonist
TransCon TLR7/8 Agonist is an investigational long-acting prodrug of resiquimod, a small molecule agonist of Toll-like receptors (TLR) 7 and 8 designed to provide sustained activation of intratumoral antigen-presenting cells driving tumor antigen presentation and induction of immune stimulatory cytokines for weeks or months with a single intratumoral injection.

Ascendis Pharma is currently conducting a Phase 1/2 study, called the transcendIT-101 Study (ClinicalTrials.gov Identifier: NCT04799054), to evaluate TransCon TLR7/8 Agonist as monotherapy or in combination with pembrolizumab in dose escalation and dose expansion cohorts. The primary objectives are to evaluate safety and tolerability and to define the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of TransCon TLR7/8 Agonist alone or in combination with pembrolizumab.

PureTech Founded Entity Karuna Therapeutics and Zai Lab Announce Strategic Collaboration for Development, Manufacturing, and Commercialization of KarXT in Greater China

On November 9, 2021 Karuna Therapeutics, Inc. (NASDAQ: KRTX), a clinical-stage biopharmaceutical company driven to create and deliver transformative medicines for people living with psychiatric and neurological conditions, and Zai Lab Limited (NASDAQ: ZLAB; HKEX: 9688), a patient-focused, innovative, commercial-stage, global biopharmaceutical company, reported their entry into an exclusive license agreement for the development, manufacturing, and commercialization of KarXT (xanomeline-trospium) in Greater China, including mainland China, Hong Kong, Macau, and Taiwan (Press release, PureTech Health, NOV 9, 2021, View Source [SID1234594854]).

KarXT is an oral, investigational M1/M4-preferring muscarinic agonist that stimulates receptors in the central nervous system implicated in various psychiatric conditions. KarXT was designed to unlock the therapeutic potential of xanomeline, which demonstrated significant benefits in reducing symptoms of psychosis in Phase 2 studies in schizophrenia and Alzheimer’s disease, while ameliorating side effects seen in earlier studies. In the Phase 2 EMERGENT-1 trial, KarXT demonstrated clinically meaningful and statistically significant improvements in the primary endpoint of Positive and Negative Syndrome Scale (PANSS) total score, and in key secondary endpoints, including PANSS-positive subscore and PANSS-negative subscore, at week 5, and was generally well-tolerated.

Karuna is evaluating KarXT in late-stage clinical trials for the treatment of schizophrenia and psychosis in Alzheimer’s disease. The EMERGENT program, the clinical program evaluating KarXT for the treatment of schizophrenia, is underway. The EMERGENT program is comprised of the previously completed Phase 2 EMERGENT-1 trial and four ongoing Phase 3 trials, with data from EMERGENT-2 and EMERGENT-3, the two Phase 3 acute efficacy and safety trials, expected in mid-2022 and in the second half of 2022, respectively. Karuna plans to initiate the Phase 3 ARISE trial evaluating KarXT as an adjunctive treatment for schizophrenia in adults who inadequately respond to atypical antipsychotics in the fourth quarter of 2021. Additionally, Karuna also plans to initiate a Phase 3 program evaluating KarXT for the treatment of psychosis in Alzheimer’s disease in mid-2022 following encouraging results from the completed Phase 1b healthy elderly volunteer trial, which suggest that potentially therapeutic doses of KarXT can be administered to elderly adults while maintaining a favorable tolerability profile. Zai Lab will work with Karuna to design the optimal strategy to accelerate the development and regulatory timeline of KarXT in Greater China.

Under the terms of the agreement, Karuna will receive a $35 million upfront payment and is eligible to receive up to an additional $80 million in development and regulatory milestones. Karuna is also eligible to receive up to $72 million in sales milestones and low-double-digit to high-teens tiered royalties based on annual net sales of KarXT in Greater China. Zai Lab will fund substantially all development, regulatory, and commercialization activities in Greater China.

"We are thrilled to collaborate with Zai Lab, who shares our commitment to bringing transformative medicines to people living with psychiatric conditions globally," said Steve Paul, M.D., chief executive officer, president, and chairman of Karuna Therapeutics. "With their proven record of successfully developing and commercializing novel therapies in Greater China, we believe that Zai Lab is the ideal partner to expand the global footprint for KarXT alongside our ongoing efforts in the U.S., with the goal of providing meaningful treatments to millions of people living with mental illness globally."

"Our collaboration with Karuna is a significant milestone for Zai Lab, marking the expansion and diversification of our development and commercial portfolio into neuroscience, our fourth therapeutic area," said Samantha Du, Ph.D., founder, chairperson and chief executive officer of Zai Lab. "KarXT is well positioned to serve as the anchor asset in our new neuroscience franchise. Zai Lab’s mission is to deliver innovative medicines to address unmet medical needs of patients, and we look forward to working with Karuna to bring KarXT to patients in need in Greater China as soon as possible."

"There is a significant need for new and more effective therapies with improved safety to treat serious psychiatric conditions in Greater China," said Gang Wang, M.D., Director of National Clinical Research Center for Mental Disorders, Dean of Beijing Anding Hospital, Capital Medical University. "Currently, more than 8 million people in Greater China are living with schizophrenia, yet fewer than half are receiving treatment, and even fewer are obtaining adequate symptom improvement from current treatment. We believe KarXT has the potential to provide a meaningful new treatment option for many patients living with schizophrenia and other conditions with disabling symptoms of psychosis."

Goldman Sachs & Co. LLC is acting as financial advisor to Karuna Therapeutics.

About KarXT

KarXT (xanomeline-trospium) is an oral, investigational M1/M4-preferring muscarinic acetylcholine receptor agonist in development for the treatment of psychiatric and neurological conditions, including schizophrenia and dementia-related psychosis. KarXT preferentially stimulates muscarinic receptors in the central nervous system implicated in these conditions, as opposed to current antipsychotic medicines, which bind to the D2 dopamine receptor. KarXT has the potential to usher in a new class of treatment for schizophrenia and dementia-related psychosis based on its differentiated mechanism of action.

Manufacture of Carina’s LGR5 CAR-T has begun with CellVec contracted to produce GMP-grade lentivirus constructs

On November 9, 2021 Singapore-based CellVec reported that it will manufacture clinical-grade lentivirus – the first critical step in making LGR5 CAR-T cells for a first-in-human clinical trial for patients with advanced colorectal (bowel) cancer in late 2022 (Press release, Carina Biotech, NOV 9, 2021, View Source [SID1234594853]).

Lentiviruses are widely used as a tool to deliver genes of interest to cells. In this case, the lentivirus transduces (or inserts) a group of genes to a patient’s T cells (immune cells), which turn the T cells into cancer-killing CAR-T cells targeting LGR5, a cancer stem cell marker found on colorectal cancer and other cancers.

Professor Simon Barry, Carina’s Vice President of Cell Therapy Manufacturing, said: "We are delighted to be working with CellVec because of their outstanding track record and expertise. Their flexibility and willingness to incorporate Carina’s proprietary manufacturing process was an important consideration in the selection of CellVec as our service provider."

"The partnership with Carina Biotech marks a significant milestone for us to facilitate the furtherance of gene therapies. We look forward to supporting Carina in the successful development of its LGR5 CAR-T cells," said Dr Ang Peng Tiam, Chairman of CellVec and Medical Director of Parkway Cancer Centre.

Carina’s LGR5 CAR-T cells are targeted at LGR5, a cancer stem cell marker that is highly expressed on colorectal cancer (and other cancers). Colorectal (bowel) cancer is the deadliest cancer for Australians aged 25-34 and Australia’s second deadliest cancer overall.

Young-onset colorectal cancer is often diagnosed at later stages, which have a much poorer prognosis.

Carina Biotech CEO, Dr Deborah Rathjen, said:

"We are continuing to see impressive results with our LGR5 CAR-T cell in pre-clinical testing. After our recent successful capital raise and welcoming new impact investors to our company, we are on track for a pre-IND submission in Q2 of 2022 and an IND submission to the FDA in the second half of 2022. These are important milestones towards the initiation of a Phase I/II clinical trial in patients with advanced colorectal cancer."

About LGR5
LGR5 is a cancer stem cell marker that is highly expressed on advanced colorectal cancer and some other cancers. In colorectal cancer patients, LGR5+ expression has been correlated with a particularly poor prognosis.

Cancer stem cells are a small sub-population of cells within a tumour with the ability to self-renew, differentiate into the many cell types of a tumour, initiate new tumours, and resist chemotherapy and radiotherapy (leading to relapses).

By targeting cancer stem cells, it is hoped that this therapy will reduce the tumour’s ability to generate new cancer cells, resulting in durable tumour suppression and preventing the relapses that are very common in patients with colorectal cancer.

Carina’s pre-clinical studies of the LGR5-targeted CAR-T cell have shown highly promising results with complete tumour regression and no tumour recurrence. They have also demonstrated impressive tumour access and prolonged CAR-T cell survival.

There are five approved CAR-T therapies available in the US today – all for blood cancers. One of these has been approved for use in Australia (Kymriah for the treatment of relapsed/refractory B cell acute lymphoblastic leukemia and large B cell lymphoma).

All five CAR-T therapies are generating transformational outcomes for patients with blood cancers that have failed multiple prior lines of therapy.

ADC Therapeutics to Participate in the Jefferies London Healthcare Conference

On November 9, 2021 ADC Therapeutics SA (NYSE: ADCT), a commercial-stage biotechnology company improving the lives of those affected by cancer with its next-generation, targeted antibody drug conjugates (ADCs) for patients with hematologic malignancies and solid tumors, reported that Chris Martin, PhD, Chief Executive Officer, will participate in a fireside chat at the Jefferies London Healthcare Conference on Tuesday, November 16th at 11:20 a.m. GMT / 6:20 a.m. EST (Press release, ADC Therapeutics, NOV 9, 2021, View Source [SID1234594852]).

A live webcast of the presentation will be available via the Events & Presentations page in the Investors section of ADC Therapeutics’ website, ir.adctherapeutics.com. A replay of the webcast will be available for approximately 30 days.

Chemomab to Present at Stifel 2021 Virtual Healthcare Conference

On November 9, 2021 Chemomab Therapeutics, Ltd. (Nasdaq: CMMB) (Chemomab), a clinical-stage biotech company focused on the discovery and development of innovative therapeutics for fibrotic and inflammatory diseases with high unmet need, reported it will host a live presentation and participate in 1-on-1 investor meetings at Stifel’s 2021 Virtual Healthcare Conference (Press release, Chemomab, NOV 9, 2021, View Source [SID1234594851]).