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Merck Enters into Exclusive Global License Agreement with Hansoh Pharma for Investigational Oral GLP-1 Receptor Agonist

On December 18, 2024 Merck (NYSE: MRK), known as MSD outside of the United States and Canada, and Hansoh Pharma, a Chinese biopharmaceutical company, reported that they have entered into an exclusive global license agreement for HS-10535, an investigational preclinical oral small molecule GLP-1 receptor agonist (Press release, Merck & Co, DEC 18, 2024, View Source [SID1234649195]).

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"We continue to leverage science-driven business development to augment and complement our robust pipeline," said Dr. Dean Y. Li, president, Merck Research Laboratories. "Through this agreement, we aim to build on our experience targeting incretin biology to evaluate HS-10535 and its potential to provide additional cardiometabolic benefits beyond weight reduction."

Under the agreement, Hansoh Pharma has granted Merck an exclusive global license to develop, manufacture and commercialize HS-10535. Hansoh Pharma will receive an upfront payment of $112 million and is eligible to receive up to $1.9 billion in milestone payments associated with the development, regulatory approval and commercialization of the candidate, as well as royalties on sales. Hansoh Pharma may co-promote or solely commercialize HS-10535 in China subject to certain conditions. Merck will record a pre-tax charge of $112 million, or $0.04 per share, to be included in GAAP and non-GAAP results in the fourth quarter of 2024.

"We are pleased to announce the in-license of our oral GLP-1 by Merck, a company with established leadership in cardiometabolic diseases," said Ms. Eliza Sun, Executive Director of the Board, Hansoh Pharma. "Hansoh Pharma is becoming an emerging leader in metabolic diseases, and we see Merck’s expertise and capabilities as key to accelerating the development of this promising asset for patients worldwide."

Coherus to Present Final Phase 2 Casdozokitug Combination Data in Patients with Metastatic Hepatocellular Carcinoma at ASCO-GI 2025

On December 18, 2024 Coherus BioSciences, Inc. ("Coherus," NASDAQ: CHRS) reported that an abstract highlighting final clinical and biomarker data from its Phase 2 clinical trial evaluating casdozokitug (casdozo), a selective and potent IL-27-antagonistic antibody, in combination with atezolizumab (atezo) and bevacizumab (bev) in treatment naïve patients with unresectable locally advanced or metastatic hepatocellular carcinoma (HCC), has been selected for a poster presentation at the upcoming 2025 ASCO (Free ASCO Whitepaper) GI Annual Meeting, being held January 23-25, 2025, in San Fransisco, CA (Press release, Coherus Biosciences, DEC 18, 2024, View Source [SID1234649194]).

"Casdozo is a first-in-class antibody, and in oncology, is the first IL-27 cytokine antagonist to demonstrate monotherapy responses and immune activation with a safety profile that lends itself to combination," said Rosh Dias, M.D., Coherus’ Chief Medical Officer. "We look forward to sharing the final data from this Phase 2 combination study of casdozo with standard of care with the medical community at the upcoming 2025 ASCO (Free ASCO Whitepaper)-GI annual meeting. We now have data across several tumor types for casdozo demonstrating clinical activity. We are particularly excited about HCC given the strong preclinical package for targeting IL-27 in liver cancer and now translation to the clinic."

Coherus has initiated a new randomized Phase 2 study (NCT06679985) evaluating casdozo, in combination with bevacizumab and toripalimab, Coherus’ next-generation anti-PD-1 monoclonal antibody, in participants with first-line HCC. This randomized, parallel, open-label Phase 2 study is designed to evaluate the safety, efficacy, and Project Optimus1 dosing of the triplet combination. The study is expected to enroll up to 72 patients, who will be randomized to receive one of two biologically active doses of casdozo with toripalimab plus bevacizumab or toripalimab plus bevacizumab without casdozo.

"Advancing casdozo development in first-line HCC with a randomized Phase 2 combination study marks a significant milestone in our strategic path to progress our clinical pipeline, which is focused on overcoming immune suppression in the tumor microenvironment to extend survival and improve outcomes for patients and pursuing new indications for toripalimab in the U.S.," continued Dr. Dias. "Casdozo has shown encouraging responses in the first line setting when added to the existing standard of care, atezolizumab and bevacizumab, and we’re excited to build upon these data with this new Phase 2 study evaluating casdozo in combination with toripalimab and bevacizumab."

In the Phase 3 HEPATORCH study, conducted by Junshi Biosciences, patients with advanced HCC treated with toripalimab combined with bevacizumab as a first-line therapy showed significantly better clinical efficacy than sorafenib monotherapy.2 HEPATORCH patients showed an objective response rate of 25.3% versus 6.1% in the sorafenib group, a median progression-free survival of 5.8 months, and a median overall survival of 20 months, compared to 4 and 14.5 months, respectively, for the sorafenib group.3 Toripalimab in combination with bevacizumab was well tolerated, with a toxicity profile consistent with the known toxicity profile of each monotherapy, with no new safety signals identified.3 The results of the HEPATORCH study support the clinical study of toripalimab in combination with bevacizumab as a new first-line treatment option for advanced HCC which, along with the results from the Phase 2 casdozo study reported to date, support pursuing a triple combination of casdozo with toripalimab plus bevacizumab in patients with advanced or metastatic HCC.

ASCO-GI 2025 Presentation Details

Title: Results from a phase 2 study of triplet blockade of the IL-27, PD-(L)1, and VEGF pathways with casdozokitug (casdozo, CHS-388) in combination with atezolizumab and bevacizumab in patients with unresectable, locally advanced or metastatic hepatocellular carcinoma (uHCC)
Lead Author: Daneng Li, City of Hope National Comprehensive Cancer Center
Abstract #: 605
Poster Session B: Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract
Date and Time: Friday, January 24, 2025; 11:30 a.m. – 1:00 p.m. PT

Hepatobiliary cancers include a spectrum of invasive carcinomas arising in the liver (hepatocellular carcinoma; HCC), gall bladder, and bile ducts (collectively called biliary tract cancers). The most common type of primary liver cancer in adults is HCC (accounting for ~90%), which is the third leading cause of cancer-related deaths worldwide. According to the NCI Surveillance, Epidemiology and End Results Program (SEER), there will be an estimated 41,630 new cases and 29,840 deaths from liver and intrahepatic bile duct cancer in the US in 2024.4 The U.S. 5-year relative survival rate for liver and intrahepatic bile duct cancer is 21.7%.4 The liver cancer treatment pattern has changed in recent years with the emergence of immunotherapy combinations and will continue to evolve as more treatment options become available for these highly lethal cancers.

Collaboration with Revolution Medicines to Study Biomarkers for RAS(ON) Multi-Selective Inhibitor in Pancreatic Cancer

On December 18, 2024 Break Through Cancer reported to have launched a collaborative cohort for a Phase 1 study of RMC-6236, a compound developed by Revolution Medicines that is designed to suppress multiple RAS proteins that drive human cancers, including pancreatic cancer, non-small cell lung cancer and colorectal cancer (Press release, Break Through Cancer, DEC 18, 2024, View Source;utm_medium=rss&utm_campaign=collaboration-with-revolution-medicines-to-study-biomarkers-for-rason-multi-selective-inhibitor-in-pancreatic-cancer [SID1234649193]).

The ongoing phase 1 trial of RMC-6236 (NCT05379985) is exploring the safety, tolerability and antitumor activity of RMC-6236 in patients with common KRAS mutations (including G12D, G12V and G12R) in metastatic pancreatic ductal adenocarcinoma (PDAC)— the most common and highly aggressive type of pancreatic cancer, with an average 5-year survival rate of only 3% for metastatic cases. Patient blood and tumor tissue samples from a dedicated collaboration cohort within this trial will be analyzed by The Conquering KRAS in Pancreatic Cancer TeamLab, funded jointly by Break Through Cancer and the Lustgarten Foundation, using advanced multi-omic and spatial profiling approaches to search for biomarkers able to predict tumor response and how cancer cells adapt to the therapy. Such biomarkers are being studied to help doctors quickly know if a patient is or is not responding to a therapy, and whether they would benefit from combination therapies.

Beyond assessing patient outcomes, the trial is uniquely designed to deepen the understanding of the biology of KRAS-mutant pancreatic cancers. By studying patient samples and biopsies in the lab, researchers will use advanced technologies to explore how PDAC evolves under treatment, the biological impact of RAS inhibition, and the mechanisms underlying resistance. This comprehensive approach will provide critical insights into the complex interplay of tumor biology and drug response.

Cancer-causing RAS proteins drive a significant number of all human cancers, including over 90% of PDAC, and many KRAS G12 mutations in particular are prevalent in human cancers. Many KRAS-targeted cancer therapies target only single KRAS mutations, while RMC-6236 was designed to inhibit the full spectrum of cancer-causing KRAS mutations, as well as other cancer-causing RAS family member mutations as well.

"We’re delighted to have the opportunity to work with Break Through Cancer and the Lustgarten Foundation on this unique cohort within our Phase 1 study for RMC-6236," said Wei Lin, M.D., Chief Medical Officer at Revolution Medicines. "The funded investigators at Break Through Cancer will use the latest scientific techniques to examine the biological effects of RMC-6236 on pancreatic tumors in patients in our clinical trial. We hope to glean insights into the mechanisms of response and resistance to RMC-6236, which will guide us to develop potential combination therapies based on our RAS(ON) inhibitors to improve patient outcomes."

The multi-center trial is being conducted by Revolution Medicines with clinical investigators at Break Through Cancer participating institutions, including Dana-Farber Cancer Institute, Johns Hopkins Kimmel Cancer Center, The University of Texas MD Anderson Cancer Center, and Memorial Sloan Kettering Cancer Center. The work is powered by Break Through Cancer’s TeamLab model of "radical collaboration," which enables real-time data and discovery sharing in laboratories across these clinical sites and in MIT’s Koch Institute for Integrative Cancer Research. Alongside this trial, TeamLab members are also investigating mechanisms of resistance to RMC-6236 and are searching for additional signaling pathways that could be promising targets for future therapeutics.

"Our mission is to drive innovation through collaboration, and this trial represents an extraordinary opportunity to do just that," said Tyler Jacks, president of Break Through Cancer; founding director of MIT’s Koch Institute for Integrative Cancer Research; David H. Koch (1962) Professor of Biology. "Together with Revolution Medicines and our TeamLab investigators, we’re applying advanced technologies and multi-institutional expertise to tackle one of the toughest challenges in oncology – pancreatic cancer.

ALX Oncology to Present Updated Results from Phase 2 ASPEN-06 Clinical Trial of Evorpacept in Patients with HER2-Positive Gastric Cancer in Oral Presentation at 2025 ASCO Gastrointestinal Cancers Symposium

On December 18, 2024 ALX Oncology Holdings Inc. ("ALX Oncology" or "the Company") (Nasdaq: ALXO), a clinical-stage biotechnology company advancing therapies that boost the immune system to treat cancer and extend patients’ lives, reported that the updated results from its Phase 2 ASPEN-06 clinical trial have been accepted for oral presentation at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium, which will be held in San Francisco from January 23 – 25, 2025 (Press release, ALX Oncology, DEC 18, 2024, View Source [SID1234649192]).

ASPEN-06 is a randomized, multi-center, international trial (NCT05002127) evaluating evorpacept, ALX Oncology’s investigational CD47-blocking therapeutic that uniquely combines a high-affinity CD47-binding domain with an inactivated proprietary Fc domain, in combination with trastuzumab, CYRAMZA (ramucirumab) and paclitaxel (collectively, TRP) against TRP alone for the treatment of patients with HER2-positive gastric/gastroesophageal junction cancer, where all patients had received an anti-HER2 agent in prior lines of therapy.

The updated results from the ASPEN-06 study will be detailed in the following oral presentation:

Title: Final analysis of the randomized phase 2 part of the ASPEN-06 study: A phase 2/3 study of evorpacept (ALX148), a CD47 myeloid checkpoint inhibitor, in patients with HER2-overexpressing gastric/gastroesophageal cancer (GC)
Abstract Number: 332
Presenter: Kohei Shitara, MD, Director of the Department of Gastrointestinal Oncology, at National Cancer Center Hospital East, Kashiwa in Japan
Presentation Date and Time: Thursday, January 23, 2025, from 9:15 a.m. – 10:00 a.m. PST
Session Information: Rapid Oral Abstract Session A: Cancers of the Esophagus and Stomach
Location: Level 2 Ballroom

Copies of the presentations will be available on the Publications section of ALX Oncology’s website following presentation at the meeting.

Clarity expands its pipeline with a novel optimised FAP-targeted radiopharmaceutical

On December 18, 2024 Clarity Pharmaceuticals (ASX: CU6) ("Clarity" or "Company"), a clinical-stage radiopharmaceutical company with a mission to develop next-generation products that improve treatment outcomes for children and adults with cancer, reported the expansion of its pipeline with a novel FAP-targeted radiopharmaceutical for the diagnosis and treatment of cancer (Press release, Clarity Pharmaceuticals, DEC 18, 2024, View Source [SID1234649191]).

FAP is expressed on cancer associated fibroblasts (CAFs), a particular cell type found in the tumour microenvironment (cancer ‘infrastructure’ called the tumour stroma). CAFs are found in a broad range of cancers (e.g. breast, colorectal, pancreatic, lung, brain and ovarian cancers), but only minimally in normal tissue, making FAP a promising pan-cancer target for both imaging and treatment of cancers1. CAFs form part of the environment surrounding the cancer cells, and they can promote cancer growth and the spread of the tumour throughout the body2. Targeting the tumour stroma is an alternative way to treat cancer whereby the architecture of the tumour mass is targeted rather than the tumour cells directly.

Clarity’s Targeted Copper Theranostic (TCT) targeting FAP was developed at the benchtop of Australian science, with a clear understanding of other FAP-targeted radiopharmaceuticals in development and the intent of overcoming the low uptake and retention of these agents in tumours. This was achieved by utilising some novel chemistry, and by combining an industry leading FAP inhibitor with the proprietary SAR chelator technology. The SAR Technology enables the use of copper-64 (64Cu) for imaging and copper-67 (67Cu) for the targeted treatment of various cancers.

Similar to how Clarity developed its PSMA-targeted prostate cancer agent as a dimer, SAR-bisPSMA, which was designed to improve tumour uptake and retention, the Company created a novel dimer for its FAP-targeted radiopharmaceutical, SAR-bisFAP. With the benefit of comparing this novel molecule to other FAP radiopharmaceuticals in development as well as to a monomer equivalent (SAR-monoFAP), the dimer SAR-bisFAP has shown increased tumour uptake and retention over 24 hours in pre-clinical models.In addition to comparing the mono and dimer versions of the product, Clarity compared the dimer, 64Cu-SAR-bisFAP, to an industry standard FAP-targeted monomer called 68Ga-FAPI-46. Using a FAP-expressing melanoma cell line (SK-MEL187) in this experiment, at 1-hour post-injection 64Cu-SAR-bisFAP had approximately 4 times the uptake in the cancer compared to 68Ga-FAPI-46. The improvements in uptake and retention of 64/67Cu-SAR-bisFAP compared to first-generation FAP compounds, such as FAPI-46, are key attributes for the development of next-generation radiopharmaceuticals.

Clarity is currently conducting additional investigations to enable a Phase I clinical trial, which could commence in late 2025. Research into the potential clinical use of Clarity’s FAP agent has begun with several pre-clinical studies in diagnostics (utilising 64Cu-SAR-bisFAP), which will be followed by exploring treatment opportunities of cancers based on their unmet medical needs (using 67Cu-SAR-bisFAP).

Clarity’s Executive Chairperson, Dr Alan Taylor, commented, "Our commitment to always putting science first at Clarity has placed us in an enviable position in radiopharmaceuticals globally. This has allowed us, yet again, to create a novel product at the benchtop to overcome the shortcomings of competing radiopharmaceuticals by increasing the uptake and retention of the molecule over time. Coupled with the use of the perfect pairing of copper isotopes, this facilitates the use of same-day and next-day imaging, addressing the issue of low sensitivity of short half-life products using gallium-68 and fluorine-18, as well as potentially enhancing the therapeutic benefit through increasing the amount and retention of the product at the site of tumours. This is especially the case for FAP-targeted radiopharmaceuticals that offer so much hope as a pan-cancer but suffer the issue of low uptake and retention at the tumour site.

"We are excited to continue growing our pipeline of TCTs through our Discovery Program, utilising the unique advantages of copper isotopes, enabled by our proprietary SAR Technology. Unlike other chelator technologies that leak copper in vivo, the SAR Technology securely holds copper over time, unlocking a myriad of advantages of the "perfect pairing" of copper-64 for imaging and copper-67 for therapy, such as next-day imaging, supply, logistical and environmental advantages. Having strong intellectual property around the SAR Technology, as well as our novel products, with over 28 patent families now within the Company, we continue expanding our pipeline of next-generation radiopharmaceuticals. The development of these new products is only possible due to the utilisation of great chemistry combined with new promising targets and our proprietary chelator, thereby enabling a multitude of new products for indications with high unmet needs. By going back to the drawing board and conducting comprehensive research and testing, we were able to create a unique product that achieves the outcomes we were looking for of improving uptake and retention in tumours. The tumour targeting, retention and pharmacokinetic data we have seen to date with SAR-bisFAP is impressive, and we look forward to progressing this product in clinical trials and are excited to explore the pan-cancer targeting potential in a range of indications with high unmet needs."

About 64/67Cu-SAR-monoFAP and 64/67Cu-SAR-bisFAP
64/67Cu-SAR-monoFAP and 64/67Cu-SAR-bisFAP are unregistered products. Their safety and efficacy have not been assessed by health authorities such as the US Food and Drug Administration (FDA) or the Therapeutic Goods Administration (TGA). Outcomes from human clinical trials may differ from pre-clinical findings. There is no guarantee that these products will become commercially available.