On September 26, 2023 Kyverna Therapeutics ("Kyverna"), a clinical-stage cell therapy company with the mission of engineering a new class of therapies for serious autoimmune diseases and ElevateBio, LLC ("ElevateBio"), a technology-driven company focused on powering transformative cell and gene therapies, reported a partnership to advance process development and manufacturing to produce industry-leading Ingenui-T-derived chimeric antigen receptor (CAR) T-cell therapies (Press release, ElevateBio, SEP 26, 2023, View Source [SID1234635425]). Ingenui-T is an optimized autologous manufacturing platform developed by Kyverna to specifically address the needs of patients with autoimmune diseases, enabling a lower cost of goods and an improved patient experience.

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ElevateBio and Kyverna will implement Kyverna’s Ingenui-T platform into their process development and cell product manufacturing efforts at ElevateBio BaseCamp. BaseCamp is ElevateBio’s end-to-end genetic medicine current Good Manufacturing Practice (cGMP) manufacturing and process development business with capabilities for research, clinical, and commercial cell and gene therapies.

Building and improving on the learnings from CAR T-cell therapy in oncology, Kyverna is seeking to revolutionize the way patients with autoimmune diseases are treated. "We are excited by the potential to not only provide dramatic benefit to patients by eliminating the underlying disease pathology using CAR T-cell therapy, but also to bring innovation to other aspects of the patient journey," said Karen Walker, chief technology officer at Kyverna. "Together with ElevateBio, we aim to deliver radical benefits to patients in less time, with lower impact, and at substantially reduced cost."

"At ElevateBio, we have combined multiple next-generation technology platforms with industry-leading expertise to transform the current cell and gene therapy development paradigm," said Michael Paglia, chief operating officer at ElevateBio BaseCamp. "We are delighted to build a long-term relationship with Kyverna to optimize manufacturing processes and accelerate the development of their therapies."

About KYV-101
KYV-101 is an autologous version of a novel, fully human clinical-stage anti-CD19 chimeric antigen receptor (CAR) T-cell construct with properties well suited for use in B cell-driven autoimmune diseases, such as lupus nephritis and other B-cell driven autoimmune diseases. In a 20-patient Phase 1/2 study in oncology, expected anti-lymphoma activity was associated with a significant reduction of cytokines released that translated into a strong reduction of cytokine-driven side effects, such as the rate of immune effector cells-associated neurotoxicity syndrome (ICANS)1. The fully human anti-CD19 CAR also translated into reduced immunogenicity that favorably impacted cell persistence at one month. Kyverna recognized that these properties singled out KYV-101 as a product ideally poised for use in autoimmune disease patients, and the company obtained exclusive, worldwide licenses from the National Institutes of Health (NIH) to use this CD19 construct in both autologous and allogeneic CAR T-cell therapies.

About Ingenui-T
Ingenui-T is Kyverna’s proprietary cost-efficient autologous CAR T-cell therapy manufacturing process, designed specifically to meet the needs of autoimmune disease patients. The process incorporates components to enhance the patient experience, to accelerate product availability, as well as to reduce cost of goods associated with personalized CAR T-cell therapy manufacturing.

On September 26, 2023 Cantex Pharmaceuticals, Inc., a clinical stage pharmaceutical company focused on developing transformative therapies for cancer and other life-threatening medical conditions for which new treatments are urgently needed, and Allegheny Health Network (AHN), an academic healthcare system serving the diverse greater western Pennsylvania community that provides pioneering medical research and education programs focused on transforming healthcare, reported the initiation of a Phase 1/2 study to assess the safety and efficacy of azeliragon in patients refractory to first-line treatment of metastatic pancreatic cancer (Press release, Cantex, SEP 26, 2023, View Source [SID1234635424]).

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"We are extremely pleased to announce the initiation and patient enrollment at Allegheny Health Network, a world-class provider of cancer treatment, of this important Phase 1/2 clinical study to evaluate the safety and efficacy of azeliragon in patients refractory to first-line treatment of metastatic pancreatic cancer," said Stephen G. Marcus, M.D., Cantex’s Chief Executive Officer.

"Azeliragon inhibits activation of a receptor known as ‘RAGE’ on the surface of cancer and cells in the tumor microenvironment. RAGE has been implicated in the growth and spread of pancreatic and other cancers, their resistance to chemotherapy, and complications stemming from pancreatic and other cancers and related treatments. With this study, we seek to slow the growth and spread of pancreatic cancer while alleviating some of its disabling effects," concluded Dr. Marcus.

"Through the initiation of this Phase 1/2 study at AHN, we seek to explore the safety and efficacy of azeliragon in pancreatic cancer patients who are no longer responding to other treatments. Targeting RAGE with azeliragon, a once-daily oral medication well tolerated in previous studies, greatly merits a clinical trial in this setting," said Nathan Bahary, M.D., Academic Chief of Medical Oncology at Allegheny Health Network Cancer Institute. Amongst his various appointments, Dr. Bahary is a member of the National Cancer Institute (NCI) Pancreatic Task Force, and the NCI’s Eastern Cooperative Oncology Group (ECOG) where he serves on the ECOG GI Steering Committee.

About Azeliragon
Azeliragon is an orally administered capsule, taken once daily, that inhibits interactions of the receptor for advanced glycation end products (known as RAGE) with certain ligands, including HMGB1 and S100 proteins in the tumor microenvironment. Azeliragon was discovered by and originally under development for Alzheimer’s disease by vTv Therapeutics Inc. (NASDAQ: VTVT) from whom Cantex licensed worldwide rights to azeliragon. Clinical safety data from these trials, involving more than 2000 individuals dosed for periods up to 18 months, indicate that azeliragon is very well tolerated.

Cantex also has ongoing Phase 2 clinical trials in newly diagnosed glioblastoma, neoadjuvant therapy of breast cancer, brain metastases in combination with stereotactic radiosurgery, and an ongoing Phase 2/3 clinical trial in hospitalized COVID-19 patients to prevent acute kidney injury. These trials are based on azeliragon’s robust pre-clinical data as well as its extensive clinical safety information from randomized placebo-controlled clinical trials.

On September 26, 2023 SK Biopharmaceuticals, a global biotech focused on the research, development and commercialization of treatments for disorders of the central nervous system (CNS) and oncology, and its U.S. R&D subsidiary, Proteovant Therapeutics, reported that they will present data on the discovery and characterization of a selective IKZF2 molecular glue degrader with best-in-class potential, and on MOPED, a novel platform for the discovery of molecular glues, at the 20th Annual Discovery on Target Conference being held in Boston, September 25-28, 2023 (Press release, SK biopharmaceuticals, SEP 26, 2023, https://www.prnewswire.com/news-releases/sk-biopharmaceuticals-proteovant-therapeutics-presents-preclinical-data-on-ikzf2-protein-degrader-program-and-moped-molecular-glue-screening-platform-at-the-20th-annual-discovery-on-target-conference-301938441.html [SID1234635422]).

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These presentations are the first in a series in which the companies will unveil exciting results from its targeted protein degradation (TPD) studies and MOPEDTM Molecular Glue Screening Platform. TPD harnesses the body’s natural protein disposal system and offers the potential to develop new medicines targeting historically difficult-to-drug proteins that play an important role in causing serious diseases. SK Biopharmaceuticals and Proteovant Therapeutics are discovering and developing potential best-in-class and first-in-class degraders to engage previously undruggable targets.

"We are excited to share new data on our IKZF2 molecular glue degrader that demonstrates the potential to combine with immune checkpoint therapies for the treatment of cancer," said Donghoon Lee, President and CEO of SK Biopharmaceuticals and SK Life Science. "We are also pleased to present data showing how our MOPED platform can help find molecular glues with the potential to destroy malfunctioning proteins and kill cancer cells or inhibit their growth."

Discovery on Target Meeting Presentations:

Title: MOPED: A Novel Platform for the Discovery of Molecular Glues
Presenter: Corey Strickland, Ph.D.
Date/Time: Wednesday, September 27; 9:30 – 10:00 AM
Title: Discovery and Characterization of an IKZF2 Selective Molecular Glue Degrader with Best-in-Class Potential
Presenter: Courtney G. Havens, Ph.D.
Date/Time: Thursday, September 28; 2:50 – 3:20 PM

On September 26, 2023 Cue Biopharma, Inc. (Nasdaq: CUE), a clinical-stage biopharmaceutical company developing a novel class of injectable biologics to selectively engage and modulate disease-specific T cells directly within the patient’s body, reported that it has completed patient enrollment in its Phase 1 clinical trial (NCT03978689) evaluating CUE-101, the company’s lead interleukin 2 (IL-2)-based biologic from the CUE-100 series, in combination with KEYTRUDA (pembrolizumab) as first-line treatment for patients with human papilloma virus positive recurrent/metastatic head and neck squamous cell carcinoma (HPV+ R/M HNSCC) (Press release, Cue Biopharma, SEP 26, 2023, View Source [SID1234635421]).

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"Completing the enrollment of the recommended phase 2 dose patient expansion cohort is an important milestone as the data from this trial guides further development plans and associated discussions with the Food and Drug Administration (FDA)," said Daniel Passeri, chief executive officer of Cue Biopharma. "We believe the updated data will build upon the already promising clinical profile established to date, which has shown an enhancement of clinical efficacy with the CUE-101-pembrolizumab combination compared to pembrolizumab alone. With the strength of the data already observed with monotherapy in second line patients and beyond, combined with the promising combination data emerging in 1L with pembrolizumab, we plan to discuss potential registrational paths with the Food and Drug Administration (FDA) for CUE-101 both as a monotherapy and in combination with pembrolizumab, leveraging the Fast Track Designation previously granted to these programs."

Matteo Levisetti, M.D., chief medical officer of Cue Biopharma added, "We believe the data from our CUE-101 trial represents a potential therapeutic breakthrough for HPV+ R/M HNSCC patients, bolstering our confidence in the platform to address unmet needs of patients suffering from a myriad of cancers. The maturing clinical data for CUE-101 further supports the mechanism of action which enables selective expansion of targeted tumor-specific T cells and also provides clinical validation and de-risking of our Immuno-STAT platform. This clinical validation is also being supported by a Phase 1 trial with our second CUE-100 series biologic, CUE-102, for Wilms’ Tumor 1-expressing tumors. Data to date has demonstrated clinical evidence of anti-tumor activity across multiple indications in patients treated in the dose escalation portion of the study, and we look forward to presenting the data at SITC (Free SITC Whitepaper)."

About the CUE-100 Series
The CUE-100 series consists of Fc-fusion biologics that incorporate peptide-MHC (pMHC) molecules along with rationally engineered IL-2 molecules. This singular biologic is anticipated to selectively target, activate and expand a robust repertoire of tumor-specific T cells directly in the patient’s body. The binding affinity of IL-2 for its receptor has been deliberately attenuated to achieve preferential selective activation of tumor-specific effector T cells while reducing the potential for effects on regulatory T cells (Tregs) or broad systemic activation, potentially mitigating the dose-limiting toxicities associated with current IL-2-based therapies.

On September 26, 2023 Starpharma (ASX: SPL, OTCQX: SPHRY) reported the presentation of data that demonstrate the benefits of combining DEP irinotecan with other important classes of anti-cancer therapies, including immuno-oncology (IO) agents, in models of human colorectal cancer (Press release, Starpharma, SEP 26, 2023, View Source;mc_eid=bf52dd3418 [SID1234635420]). The data will be presented in Boston, US, at the AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper), co-hosted by the American Association For Cancer Research (AACR) (Free AACR Whitepaper), the National Cancer Institute (NCI) and the European Organisation for Research and Treatment of Cancer (EORTC) from 11 to 15 October 2023. This poster presentation is one of three by Starpharma at the AACR (Free AACR Whitepaper)-NTI-EORTC conference showcasing multiple DEP programs, including DEP irinotecan and Starpharma’s radiotheranostic, DEP HER2-zirconium.

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This DEP irinotecan combination poster builds on Starpharma’s recently released positive clinical data on DEP irinotecan in advanced colorectal cancer (CRC) and advanced platinum-resistant ovarian cancer2.

The DEP irinotecan combination data to be presented show DEP irinotecan improves the anti-tumour activity of an IO agent3 in the same class as the highly successful Merck product, Keytruda (pembrolizumab), including in models of CRC that respond poorly to IO agents.

DEP irinotecan in combination with the IO agent enhanced anti-tumour responses compared to the IO agent alone in a CRC model that is only moderately responsive to the IO agent. The combination also resulted in complete tumour regression and prolonged survival compared to the IO agent alone in this CRC model. In another model of CRC that was not responsive to the IO agent alone, the anti-tumour effects of the combination of DEP irinotecan and the IO agent were enhanced when compared with either agent alone.

DEP irinotecan’s ability to elicit an anti-cancer response to an IO agent in an otherwise non-responsive CRC tumour is significant. These improved results in CRC models provide a rationale for a potentially important new application of DEP irinotecan in combination with IO agents, which are a leading and growing class of anticancer therapies.

Importantly, 85% to 95% of CRC patients do not respond to IO agents, such as Keytruda, and this cancer remains a significant unmet medical need. These CRC patients do not respond to IO agents because their cancer is classified as microsatellite stable (MSS). These MSS cancers are more difficult to treat, more likely to recur, and typically less responsive to IO therapies than cancers that are not MSS. This DEP irinotecan poster includes new clinical data from Starpharma’s Phase 1/2 trial of the product showing that all CRC patients who responded to DEP irinotecan were MSS and, therefore, in the category that is more difficult to treat.

IO agents have changed the landscape of cancer treatment, demonstrating impressive results in treating a number of cancers, including lung cancer and melanoma, and generating over USD $60.3 billion in sales in 2021, with sales predicted to grow 14 to 17% per year to 20264.

IO anti-cancer drugs are designed to disrupt normal immune processes, allowing the body’s immune cells to effectively target and destroy cancer cells. Currently marketed IO drugs include Keytruda (Merck), Opdivo (BMS), Yervoy (BMS), Tecentriq (Genentech), and Imfinzi (AstraZeneca). The global colorectal cancer drugs market was valued at ~US$14 billion in 2023 and is forecast to reach more than US$16 billion by 20275. Immunotherapies, such as Keytruda, had approximately 25% market share in 20186.

Despite their impressive efficacy, IO agents can cause serious immune-mediated adverse events that are challenging to manage. Treatment with DEP irinotecan resulted in no immune-mediated adverse events in CRC and ovarian patients, and therefore, there was no overlap of adverse events with those reported for IO agents – another benefit for this combination application.

In addition to the promising data for DEP irinotecan in combination with the IO agent, Starpharma’s poster also includes data on DEP irinotecan in combination with AstraZeneca’s Lynparza (olaparib). Olaparib is from a class of drugs called PARP inhibitors. DEP irinotecan also showed a synergistic effect in combination with olaparib in a model of CRC. The CRC model used was resistant to olaparib alone, but the combination of DEP irinotecan and olaparib achieved increased anti-tumour effects compared to DEP irinotecan alone, and also prolonged survival.

Lynparza had global sales of more than US$2.6 billion in 20227 and is approved for use in ovarian, breast, pancreatic and prostate cancers.

The data showing DEP irinotecan enhances anti-tumour responses of the IO agent and PARP inhibitor in models of cancer, together with the promising clinical efficacy and safety profile of DEP irinotecan in CRC and ovarian cancer, provide a strong rationale for clinical evaluation of DEP irinotecan in combination with IO agents and PARP inhibitors. These combination regimens are commercially important because they increase the potential market opportunities for DEP irinotecan and illustrate synergies with successful product categories. Given these findings, Starpharma is engaging in discussions with potential commercial partners, including companies that currently market IO agents.

The above-mentioned poster is one of three posters Starpharma is presenting at the AACR (Free AACR Whitepaper)-NCI-EORTC conference in October 2023.

Thursday, 12 October (Poster Session A): A147: A HER2 targeted polylysine dendrimer nanoparticle radiotheranostic demonstrates excellent tumor accumulation, rapid clearance from circulation, and promising performance in PET-CT imaging.
Friday, 13 October (Poster Session B): B039: A phase 1/2 study of dendrimer-enhanced (DEP) SN38 (SN38-SPL9111 / DEP irinotecan) in patients with advanced solid tumours.
Saturday, 14 October (Poster Session C): C167: An SN38 dendrimer nanoparticle, DEP irinotecan (SN38-SPL9111), demonstrates efficacy in mouse models of gastrointestinal cancer and augments anti-tumor effects of immune checkpoint blockade and PARP inhibition.
Abstracts, which include a summary of the data, will be published on the conference website ahead of the conference, and the full posters will be made available by Starpharma following publication.

About DEP irinotecan

DEP irinotecan is a novel, patented, nanoparticle formulation of SN38, the active metabolite of the widely used anti-cancer drug, irinotecan (marketed as Camptosar), delivered using Starpharma’s proprietary DEP technology. Camptosar and all generic forms of conventional irinotecan carry ‘black box’ warnings mandated by the US Food and Drug Administration (FDA) for both neutropenia and severe diarrhoea, which can be dose-limiting and life-threatening. DEP irinotecan has not resulted in severe diarrhoea in Phase 2 studies. DEP irinotecan has patent filings to 2039 and up to an additional five years.

The severe diarrhoea caused by conventional irinotecan results from the production of toxic metabolites during the liver metabolism of irinotecan to SN38. DEP irinotecan was designed to eliminate the need for liver metabolism, thereby avoiding the production of toxic metabolites.

About Starpharma’s DEP irinotecan Phase 2 clinical trial

Starpharma is evaluating DEP irinotecan as both a monotherapy and in combination with 5-fluorouracil (5-FU) and leucovorin (LV), which is a standard irinotecan combination regimen used in the treatment of CRC known as "FOLFIRI". The Phase 2 DEP irinotecan trial is being conducted at multiple sites, including Guy’s Hospital in London, Beatson Cancer Centre in Glasgow, Imperial College London, and the Kinghorn Cancer Centre in Sydney.

Clinical and commercial opportunity for DEP irinotecan

The global colorectal cancer drugs market was valued at ~US$14 billion in 2023 and is forecast to reach more than US$16 billion by 20278.

Camptosar and generic forms of conventional irinotecan are standard-of-care treatments for advanced CRC, with Pfizer’s Camptosar achieving peak sales of ~US$1.1 billion. CRC accounts for approximately 10% of all new cancer diagnoses and is the second leading cause of cancer, affecting more than 1 million people annually, and is the fourth leading cause of cancer-related death.

CRC incidence is increasing markedly among younger age groups, with rates of colon cancer more than doubling in adults aged 20 to 54 since the 1990s. Studies have shown that, compared with adults born around 1950, those born around 1990 have double the risk of colon cancer and quadruple the risk of rectal cancer.