On April 17, 2023 Immutep Limited (ASX: IMM; NASDAQ: IMMP) ("Immutep" or "the Company"), a clinical-stage biotechnology company developing novel LAG-3 immunotherapies for cancer and autoimmune disease, reported the initiation of an open-label Phase II trial evaluating eftilagimod alpha (efti), a soluble LAG-3 protein and MHC Class II agonist, in combination with pembrolizumab and radiotherapy in up to 40 soft tissue sarcoma (STS) patients in the neoadjuvant (prior to surgery) setting (Press release, Immutep, APR 17, 2023, View Source [SID1234630128]).

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The investigator-initiated study (EFTISARC-NEO) will be primarily funded by the Maria Skłodowska-Curie National Research Institute of Oncology with an approved grant from the Polish government awarded by the Polish Medical Research Agency program. Immutep will provide efti at no cost as well as technical support. The trial will be led by Co-Principal Investigators, Katarzyna Kozak, M.D., Ph.D., and Paweł Sobczuk, M.D., Ph.D., medical oncologists at the Department of Soft Tissue/Bone Sarcoma and Melanoma at the Maria Skłodowska-Curie National Research Institute of Oncology.

Dr. Paweł Sobczuk, stated: "We are excited to begin this chemotherapy-free study combining radiotherapy with the novel immunotherapy, eftilagimod alpha, and pembrolizumab. Given efti’s synergistic effects with immune checkpoint inhibitors and its ability to arm, activate, and proliferate cytotoxic T cells with radiotherapy-induced cancer antigens, this combination has a strong foundation to drive effective immunity against soft tissue sarcoma, a rare and aggressive disease in immense need of new therapeutic approaches."

Efti’s targeting and unique activation of antigen-presenting cells (e.g., dendritic cells, monocytes) via MHC Class II molecules leads to broad adaptive and innate immunity to fight cancer, including proliferation of CD8+ cytotoxic T cells that can be armed with radiotherapy-induced tumour antigens. The combination of efti with radiotherapy and the anti-PD-1 therapy KEYTRUDA (pembrolizumab) has the potential to generate a robust anti-tumour immune response in the immunosuppressed tumour microenvironment (TME) of STS. This is the first time efti will be tested in the neoadjuvant setting, which importantly will provide access to tumour tissue prior to and after treatment, where the impact of this novel triple combination on the TME can be assessed.

Immutep CEO, Marc Voigt added: "Efti’s unique potential to help safely drive superior clinical efficacy for cancer patients, with and without the use of chemotherapy, is attracting increasing attention from industry and academia. We are delighted to see efti and pembrolizumab, which together have led to deep and durable responses in several difficult-to-treat advanced solid tumours, being combined with radiotherapy for the first time and hope this approach can make a difference for soft tissue sarcoma patients who have limited treatment options."

Soft tissue sarcoma (STS) represents a high unmet medical need with a poor prognosis for patients. The incidence of STS varies in different regions, with approximately 23,400 cases annually and a crude incidence of 4.7 per 100,000 in Europe, according to the RARECARE project. In the United States, the number of new STS cases is estimated to be 13,400 annually with 5,140 deaths, according to the American Cancer Society.

The dosing of the first patient is anticipated in the first half of calendar year 2023.

On April 17, 2023 Patrys reported that its deoxymab platform has been further strengthened by the granting of two new patents by the US Patent and Trademark Organisation (US PTO), providing expanded intellectual property protection until 2039 (Press release, Patrys, APR 16, 2023, View Source [SID1234630168]).

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The first patent, co-filed with Yale University, is the first US patent to be granted specifically for PAT-DX1 and PAT-DX3, the humanised forms of the original 3E10 antibody. The second patent covers the combination of deoxymabs with nanocarriers that can potentially provide a powerful new approach for treating cancer.

Patrys’ CEO and Managing Director, Dr James Campbell said:

"The granting of these two patents provides Patrys with robust intellectual property covering both the humanised form of the antibody and its conjugated form. The Company has multiple patents granted in the United States and other major jurisdictions which cover a broad range of applications for using deoxymabs to treat cancer and deliver therapeutic payloads. As well as expanding Patrys’ patent estate, these new patents provide the intellectual property coverage to enable the Company or potential partners or licensees to invest in development programs for these applications.

On April 16, 2023 As a global innovative biopharmaceutical company, Henlius reported that it is committed to offering high-quality, affordable and innovative biopharmaceuticals to patients worldwide with 5 products launched in China (Press release, Henlius Biopharmaceuticals, APR 16, 2023, View Source [SID1234630134]). Leveraging the differentiated competitive edges of its products, Henlius adopts meticulous management model and precise market strategies to optimize the commercialization layout and further extend its market reach. In the first quarter of 2023, Henlius’revenue climbed 97.2% to RMB995.7 million. With expanding sales of its flagship products including HANQUYOU and HANSIZHUANG, the company has shown continous revenue growth.

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HANQUYOU Continues to Soar

In the first quarter of 2023, Henlius’ core anti-tumour product HANQUYOU (trastuzumab, trade name in Europe: Zercepac, trade name in Australia: Tuzucip and Trastucip) extended its strong momentum, soaring by 66.7%, to RMB538.6 million.

HANQUYOU, indicated for the treatment of HER2-positive breast cancer and gastric cancer, is the first product sold and promoted in Chinese mainland by the company’s in-house commercialisation team. The 150mg/60mg dual dosage and preservative-free formulation of HANQUYOU sets it apart, leading clinical practices and providing a personalized and cost-effective treatment option for breast cancer patients of any weight. In 2022, the 24,000L production capacity of Songjiang First Plant was approved to commence the commercial production of HANQUYOU, being a driving force behind the production increase and the accerlerated commercialisation of HANQUYOU. Furthermore, Henlius continues to expand the sales network of HANQUYOU. As at the end of 2022, the copany had more than 550 sales agents for HANQUYOU, with the goal of penetrating the Chinese mainland markets with efficiency far exceeding the industry average.

HANQUYOU is the first China-developed mAb approved both in China and Europe. It was approved for commercialisation by the European Commission (EC) and NMPA in July 2020 and August 2020, respectively. In February 2023, the Biologics License Application (BLA) for HANQUYOU has been accepted by the U.S. Food and Drug Administration (FDA), which will further expand the product’s footprint in major markets of biologics in the U.S. and Europe. In addition, Henlius has aggressively pursued international commercialization of HANQUYOU, actively collaborating with global partners to bring its therapeutics to patients in the United States, Canada, Europe, and other emerging markets, covering about 100 countries and regions. Up to now, HANQUYOU has launched in over 30 countries and regions, including the United Kingdom, France, Germany, Switzerland, Australia, Finland, Spain, Singapore, Argentina and Saudi Arabia.

HANSIZHUANG Sees Unbated Growth

In the first quarter of 2023, the company’s first innovative product, HANSIZHUANG (serplulimab) achieved a domestic sales revenue of RMB249.8 million. Notably, HANSIZHUANG realized a monthly sales of over RMB100 million in March 2023 in Chinese mainland, starting a new stage of its sales growth as well as providing strong momentum for the product’s commercialization.

HANSIZHUANG was launched in China in March 2022，and has been approved for 3 indications including MSI-H solid tumour, squamous non-small cell lung cancer (sqNSCLC) and extensive stage small cell lung cancer (ES-SCLC) so far. As the world’s first anti-PD-1 monoclonal antibody (mAb) for the first-line treatment of SCLC, HANSIZHUANG set a record for SCLC immunotherapy with a median OS (overall survival) of 15.8 months. With its outstanding quality and clinical efficacy, HANSIZHUANG has earned wide recognitions from the market and has seen rapid sales uptick. At the beginning of the product’s commercialisation, an amazing "Henlius speed" has been demonstrated in the first deliveries and the first prescriptions of HANSIZHUANG, which also indicated the company’s strong commercial operation and execution. As of the end of 2022, its sales team has been expanded to approximately 400 people. With a rich experience in oncology and meticulous management model, the team has covered over 23,000 healthcare providers from nearly 1000 domestic hospitals. Looking forward, the company will continue to accelerate the market coverage and penetration of HANSIZHUANG in the areas of lung cancer, gastrointestinal and gynecological tumours.

In March 2023, the European Medicines Agency (EMA) has validated the Marketing Authorization Application(MAA) for HANSIZHUANG for the first-line treatment of ES-SCLC. Another patient has also been dosed in a head-to-head bridging trial of HANSIZHUANG versus first-line standard of care atezolizumab for ES-SCLC in the U.S. The company also plans to submit a Biologics License Application (BLA) for HANSIZHUANG in the U.S. in 2024. Meanwhile, the company continues to explore the combination therapies between HANSIZHUANG and self-developed products such as HANBEITAI, HLX07 (anti-EGFR mAb), HLX26 (anti-LAG-3 mAb), HLX208 (BRAF V600E small molecule inhibitor) and HLX60 (anti-GARP mAb) to provide better therapies for the patients, more than 10 clinical trials on immuno-oncology combination therapies are in progress in a wide variety of indications.

Looking forward, Henlius will continue to delve into the area of oncology, auto-immune and other diseases. While maximizing the commercial value of biosimilars at home and abroad, Henlius will actively explore innovation drugs and tackle unmet clinical needs by leveraging its in-house R&D capabilities supplemented by external cooperation and license-in, so as to consolidate the best-in-class capabilities of "integrated research, manufacturing and commercialisation", and achieve steady development as a larger, international and more profitable Biopharma to provide more affordable and better therapies for patients worldwide.

On April 16, 2023 Accent Therapeutics, a biopharmaceutical company developing breakthrough, oncology-focused small molecule therapies that target RNA-modifying proteins (RMPs), reported data supporting DHX9 inhibition as a novel cancer treatment approach at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2023 in Orlando, Florida (Press release, Accent Therapeutics, APR 16, 2023, View Source [SID1234630133]).

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DHX9 is a multifunctional DEAH-box RNA helicase which has been reported to play important roles in replication, transcription, translation, and RNA splicing – critical processes that contribute to maintenance of genomic stability. Microsatellite instable (MSI) tumors exhibiting defective mismatch repair (dMMR) show a strong dependence on DHX9, making the helicase an attractive target for oncology drug discovery.

"Accent is advancing the compelling and growing body of evidence linking RMPs to cancer pathobiology and demonstrating their untapped potential for addressing cancers with high unmet clinical need. Our systematic analysis of the RMP landscape has revealed several promising precision oncology targets, including DHX9. The data presented at AACR (Free AACR Whitepaper) illustrate strong proof-of-concept supporting DHX9 inhibition as a promising approach to addressing MSI tumors and validate the overall utility of RMPs as a compelling target class for oncology drug development," said Robert A. Copeland, Ph.D., President, Founder, and Chief Scientific Officer of Accent Therapeutics. "We are pleased with our rapid progress advancing from target identification to promising therapeutic programs and look forward to bringing these therapies closer to patients."

The data presented at the meeting provide compelling support for targeted inhibition of DHX9 as a novel therapeutic modality in MSI colorectal cancer (CRC) and describe the first identification of potent and selective small molecule inhibitors of DHX9 that demonstrate tumor cell killing in both in vitro and in vivo preclinical cancer models.

Informed by a proprietary crystal structure of human DHX9, Accent used structural considerations to design selective small molecule inhibitors of the protein and developed a robust assay suite to characterize inhibitor activity. Data from xenograft models demonstrate that oral administration of one such compound, ATX968, was well tolerated in vivo and induced durable tumor regression during the 28-day treatment period, with minimal tumor regrowth observed within a 28-day post treatment window. Dose dependent changes in biomarkers of DHX9 inhibition, such as circular RNA induction – which can be measured in peripheral blood, indicate a promising pharmacokinetic (PK)/pharmacodynamic (PD) profile and further validate DHX9 as a promising new oncology target.

"Our DHX9 program is one in a portfolio of high impact, RNA-modifying targets that Accent is pursuing with novel, oncology-focused small molecules," said Shakti Narayan, Ph.D., J.D., Chief Executive Officer of Accent. "This progress is a testament to our team’s ability to leverage deep insights into cancer biology and structure-based drug development to deliver new precision oncology therapies with transformative potential."

The abstract is available online as part of the annual meeting’s Proceedings supplement in AACR (Free AACR Whitepaper)’s journal, Cancer Research, and the presentation will be archived on the Accent Therapeutics website, www.accenttx.com.

Presentation details are as follows:

Title: Targeting DHX9 Inhibition as a Novel Therapeutic Modality in Microsatellite Instable Colorectal Cancer
Authors: Jennifer Castro, Matthew H. Daniels, Chuang Lu, David Brennan, Deepali Gotur, Young-Tae Lee, Kevin Knockenhauer, April Case, Jie Wu, Shane M. Buker, Julie Liu, Brian A. Sparling, E. Allen Sickmier, Stephen J. Blakemore, P. Ann Boriack-Sjodin, Kenneth W. Duncan, Scott Ribich, Robert A. Copeland
Accent Therapeutics, Lexington, MA
Abstract Number: 1136
Session Category: Experimental and Molecular Therapeutics
Session Title: Innovative Therapeutic Approaches
Session Date and Time: Sunday, April 16, 2023 3:00 – 5:00 PM ET
Session Location: Room W331, Orange County Convention Center, Orlando, Florida

About DHX9
DHX9 is a multifunctional DEAH-box RNA helicase which has been reported to play important roles in replication, transcription, translation, RNA splicing and RNA processing which contribute to DHX9’s role in maintenance of genomic stability. Overexpression of DHX9 has been observed in multiple cancer types, including colorectal cancer (CRC). In addition, microsatellite instable (MSI) tumors exhibiting defective mismatch repair (dMMR) show a strong dependence on DHX9, making this helicase an attractive target for oncology drug discovery.

On April 16, 2023 Telix Pharmaceuticals Limited (ASX: TLX, Telix, the Company) reported successful preclinical development of radiolabelled olaratumab, an antibody licensed from Eli Lilly and Company (Lilly) (Press release, Telix Pharmaceuticals, APR 16, 2023, View Source [SID1234630132]). Telix has demonstrated proof-of-concept (PoC) of using olaratumab to selectively deliver both diagnostic and therapeutic radiation to tumours as a radiopharmaceutical moiety and has produced a candidate for clinical translation. Telix will now progress to first-in-human clinical studies based on these highly encouraging results.

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In April 2022, Telix secured the exclusive worldwide rights to develop and commercialise radiolabelled forms of olaratumab for the diagnosis and treatment of human cancers.[1] Olaratumab was originally developed as a naked (non-radiolabelled) monoclonal antibody targeting Platelet Derived Growth Factor Receptor Alpha (PDGFRα), a target expressed in multiple tumour types. Olaratumab has a well-established clinical safety profile, a favourable toxicology dataset and advanced manufacturing package in relation to Lilly’s development program, which Telix expects to be able to leverage for future development as a radiopharmaceutical drug product.

Telix’s initial development PoC has focused on a rare type of cancer known as Soft Tissue Sarcoma (STS). External beam radiation is a key part of the standard of care for STS, which may therefore be a suitable clinical target for novel radionuclide therapy, particularly for alpha-emitting radionuclides. The ability of olaratumab to target PDGFRα in the STS tumour microenvironment makes it a highly novel and high-potential radiopharmaceutical candidate.

Telix has now completed its preclinical evaluation, with results sufficiently encouraging to advance development toward initial human clinical trials, in line with planned R&D expenditure for 2023/24. The agent has been assigned formal candidate status in Telix’s development pipeline (to be denoted as TLX300-CDx/TLX300 for the diagnostic/patient selection tool and therapeutic, respectively). Specifically, these studies have shown that olaratumab can be bioconjugated with multiple chelators (including Telix’s proprietary DFO-squaramide chelator), radiolabelled with zirconium-89 (89Zr) for imaging by Positron Emission Tomography (PET) and used to demonstrate specific delivery of radiation to STS cancer cells to show proof of concept in xenograft tumour mouse models. Furthermore, olaratumab radiolabelled with therapeutic radionuclide payloads has demonstrated in vivo efficacy with significant reduction in tumour volumes in relevant disease models, even after administration of a single dose. The Company is preparing to publish preliminary findings.

Telix Chief Scientist, Dr Michael Wheatcroft stated, "Building on Telix’s proven track record in acquiring and developing novel radiopharmaceutical assets, it is extremely pleasing to demonstrate the adaptation of this traditional biologic agent for future potential use as a targeted radiopharmaceutical. TLX300 will initially be evaluated in a first-in-human clinical study that is designed to inform both the potential efficacy (dosimetry) and safety profile of this research candidate as a therapeutic, demonstrating the development advantage of a theranostic approach."

About Soft Tissue Sarcoma (STS)

Soft tissue sarcoma is a complex disease that encompasses a diverse group of relatively rare cancers, with more than 50 histological subtypes. In the United States (U.S.), it is estimated that 13,040 new cases and 5,150 deaths were caused by STS in 2019, representing 0.75% of overall cancer incidence and 0.84% of overall cancer mortality.[2] In Europe, nearly 23,600 new STS cases rose annually, and the crude incidence rate was 4.7 per 100,000.[3] Approximately 39,900 new STS cases occurred nationwide in China in 2019, accounting for 1.05% of overall cancer incidence.[4] The crude incidence rate was 2.91/100,000 and generally increased with age. Standard treatment for soft tissue sarcoma includes surgery, radiation therapy and/or chemotherapy. For patients with advanced, unresectable, or metastatic disease, treatment typically involves chemotherapy with single agents (e.g., doxorubicin) or anthracycline-based combination regimens. However, the prognosis for these patients remains poor, with treated patients with metastatic disease having a median overall survival of around 12–18 months.[5]

About olaratumab

Olaratumab (previously marketed under the brand name, Lartruvo) was originally developed as a monoclonal antibody targeting PDGFRα. Olaratumab was granted "Accelerated Approval" in the U.S. and "Conditional Approval" in the EU based on Phase II trial data which showed a 1-year survival benefit in patients with STS, when given in combination with standard chemotherapy. Olaratumab was voluntarily withdrawn from the market by Lilly following the failure of the Phase III ANNOUNCE clinical trial, in which olaratumab did not improve survival for patients.