On April 12, 2022 TriSalus Life Sciences, an immunotherapy company on a mission to extend and improve the lives of patients living with liver and pancreatic tumors, reported a strategic collaboration with Lifespan, a health system, affiliated with The Warren Alpert Medical School of Brown University (Press release, TriSalus Life Sciences, APR 12, 2022, View Source [SID1234612131]).

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Over the next two years, TriSalus will develop and run a new on-campus laboratory to launch immunotherapeutic research that leverages Lifespan’s clinical and research infrastructure, including its state-of-the-art vivarium. TriSalus’ pre-clinical team, supported by the company’s Cranston, Rhode Island-based clinical team, will lead this research to further develop TriSalus’ therapeutic platform and advance medical knowledge of the barriers that can limit the effectiveness of immuno-oncology treatments for patients with liver and pancreatic tumors. The lab will also be used to support clinical trials to test this novel immunotherapy approach for patients with liver and pancreas tumors.

"Supporting research with the potential to transform patient care is a core tenet of our focus to accelerate progress as Rhode Island’s leading cancer research institution," said Michael Henderson, JD, MS, LLM, vice president for research and chief research officer, Lifespan. "Partnering with local industry leaders like TriSalus offers an ideal opportunity to not only better understand the challenges facing patients with liver and pancreatic tumors, but also the possibility to facilitate new treatment options."

While immunotherapy has yielded significant progress in cancer treatment, key barriers such as intratumoral pressure and tumor-induced immunosuppression limit the effectiveness of these treatments for patients with liver and pancreatic tumors.

"Due to the unique environment of their tumors, many patients with liver and pancreatic tumors are unable to fully benefit from traditional delivery of immunotherapy," said William G. Cioffi, MD, FACS, surgeon-in-chief, The Miriam and Rhode Island Hospitals, and J. Murray Beardsley Professor and chairman of the department of surgery at The Warren Alpert Medical School of Brown University. "Our clinicians are eager to support research like TriSalus’ that has the potential to advance innovative solutions to improve outcomes for patients living with these hard-to-treat cancers."

TriSalus’ platform seeks to address treatment challenges for liver and pancreatic tumors by integrating immunotherapy with innovative drug delivery technology. The company is studying the ability of SD-101, a potentially first-in-class, investigative toll-like receptor 9 (TLR9) agonist, to reactivate the immune system within the liver and pancreas and enable more durable responses to other immunotherapeutics, such as checkpoint inhibitors. The platform utilizes TriSalus’ proprietary Pressure-Enabled Drug Delivery (PEDD) method of administration, which modulates pressure and flow within blood vessels to overcome intratumoral pressure and ultimately improve the amount of therapy delivered to the tumor.

"Building an on-site research presence at Lifespan equips us to continue clinical and pre-clinical studies to validate that our tailored, organ-specific treatment approaches may allow patients living with liver and pancreatic tumors to respond more reliably to immunotherapy," said Steven C. Katz, MD, FACS, TriSalus Chief Medical Officer.

The Lifespan collaboration also extends TriSalus’ ongoing work with leading cancer research centers to bring new treatments to patients living with liver and pancreatic tumors. For example, the first Pressure Enabled Regional Immuno-Oncology study, PERIO-01 (NCT04935229), is underway and evaluating the efficacy of SD-101 in combination with checkpoint inhibitors in patients with uveal melanoma with liver metastases. PERIO-02 (NCT05220722), recently opened for patients with hepatocellular carcinoma and intrahepatic cholangiocarcinoma. A separate trial for locally advanced pancreatic ductal carcinoma is also in development. Learn more at trisaluslifesci.com and periotrial.com.

On April 12, 2022 Bio-Path Holdings, Inc., (NASDAQ: BPTH), a biotechnology company leveraging its proprietary DNAbilize antisense RNAi nanoparticle technology to develop a portfolio of targeted nucleic acid cancer drugs, reported a poster highlighting preclinical BP1003 data at the 2022 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting (Press release, Bio-Path Holdings, APR 12, 2022, View Source [SID1234612112]).

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The poster, titled "Targeting STAT3 with novel liposome-incorporated antisense oligonucleotide technology enhances the efficacy of paclitaxel (taxol) or 5-fluorouracil (5-FU) in breast and ovarian cancer cells," was presented by Dr. Maria Gagliardi, Research Scientist at Bio-Path Holdings.

"We are particularly pleased to have these preclinical data of BP1003 plus chemotherapy combinations against breast and ovarian cancer cells highlighted in a poster before an audience of the world’s leading cancer researchers at this important scientific meeting. The data show that BP1003 enhances the efficacy of current standard of care chemotherapies in these difficult to treat solid tumor cancers," stated Peter Nielsen, President and Chief Executive Officer of Bio-Path Holdings. "We look forward to filing an Investigational New Drug (IND) application for BP1003 and to initiating a clinical study in patients with advanced solid tumors."

STAT3 is a transcription factor that regulates various tumorigenic processes, such as tumor proliferation, metastasis and drug resistance. Its overexpression and aberrant activation characterize many cancers, including breast, lung, ovarian, liver and colon cancer. Activation of the STAT3 pathway in breast and ovarian cancer cells promotes tumor initiation, migration, and taxol resistance. STAT3 also contributes to epithelialmesenchymal transition and promotes 5-FU resistance in colorectal cancer cells. Its role in numerous malignancies made STAT3 a potential cancer therapeutic target.

BP1003, a novel liposome-incorporated STAT3 antisense oligodeoxynucleotide, efficiently reduces STAT3 expression and enhances the sensitivity of breast and ovarian cancer cells to taxol and 5-FU. These results are in line with previous work in which BP1003 plus gemcitabine displayed enhanced anti-tumor activity in pancreatic ductal adenocarcinoma. Together these results strongly suggest that BP1003 combination therapy is a novel strategy for patients with advanced solid tumors.

On April 12, 2022 Keymed Biosciences (2162.HK) reported that its new drug candidate CMG901 (the "Claudin 18.2 antibody drug conjugates") for the treatment of gastric cancer and gastroesophageal junction adenocarcinoma has been granted the Orphan-drug Designation by the Food and Drug Administration of the United States (the "FDA") recently (Press release, Keymed Biosciences, APR 12, 2022, View Source [SID1234612107]). Previously, in March 2021, the Company received the clinical trial application approval of CMG901 from the FDA for the clinical trial in gastric cancer and gastroesophageal junction adenocarcinoma in the United States.

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"The ongoing Phase 1 trial of CMG901 demonstrated promising anti-tumor activity in advanced gastric and GEJ adenocarcinoma patients," said Joy Yan, MD, PhD, Keymed Biosciences Chief Medical Officer, "We look forward to working closely with the FDA to finish the design of the global pivotal trial in Claudin 18.2-positive advanced gastric and GEJ adenocarcinoma".

About CMG901

CMG901 is the first Claudin 18.2 ADC to obtained IND approval in China and in the U.S. CMG901 consists of three components: a monoclonal antibody targeting Claudin 18.2, a cleavable linker and a potent cytotoxic payload (MMAE). Claudin 18.2 has been identified as a highly selective molecule that is widely expressed in multiple solid tumors, including gastric cancer and pancreatic cancer, suggesting that Claudin 18.2 is an ideal target for tumor therapeutic development.

CMG901 can cause tumor cell death by several mechanism:

CMG901 binds to Claudin 18.2 positive cell via its monoclonal antibody portion. After binding, CMG901 will be internalized into lysosome by tumor cells and release the cytotoxic payload, leading to cell cycle arrest and apoptosis of the tumor cells.
CMG901 can stimulate cellular and soluble immune effectors that activate antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) to destroy the Claudin 18.2 positive cells.
Preclinical studies suggest that CMG901 can effectively kill gastric cancer cells with much stronger antitumor potency than zolbetuximab analog or the unconjugated antibody of CMG901. Meanwhile, CMG901 also shown good tolerance and favorable safety profile in preclinical studies.

On April 12, 2022 Phanes Therapeutics, Inc. (Phanes), an emerging leader in innovative discovery research and development in immuno-oncology, reported that the company has been granted a patent (Patent No. US 11,299,550 B2) on its anti-CD73 antibodies by the United States Patent and Trademark Office (USPTO) (Press release, Phanes Therapeutics, APR 12, 2022, View Source [SID1234612106]). The patent includes the invention of PT199, for which the company just received clearance from the US Food and Drug Administration to commence Phase I studies.

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PT199 is an anti-CD73 mAb with a differentiated mechanism of action and is designed to counter the adenosine-mediated immunosuppressive tumor microenvironment. PT199 fully inhibits both soluble and membrane-bound CD73, unlike some other CD73 inhibitors which exhibit incomplete inhibition. Moreover, at higher concentrations, no loss of inhibition or "hook effect" is observed with PT199. Hence, PT199 addresses the limitations of current CD73 inhibitors and is expected to increase antitumor immune activation, and potentially offer a new treatment option for cancer patients.

The multi-center Phase I clinical trial of PT199 is designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of PT199 alone and in combination with a PD-1 inhibitor, in patients with locally advanced or metastatic solid tumors that have progressed after all available standard therapy or for which standard therapy has proven to be ineffective, intolerable, or is considered inappropriate.

"This couldn’t have come at a better time," said Dr. Ming Wang, PhD, MBA, Founder and CEO of Phanes Therapeutics. "This will be a transformational year for Phanes as we expand from a research to a clinical stage organization. We expect to file two additional INDs in 2022, both first-in-class bispecific antibody programs, and anticipate receiving more issued patents."

On April 12, 2022 ZielBio, Inc., a clinical stage biotechnology company discovering new treatments for cancer and other serious diseases through its innovative ZielFind drug discovery platform, reported that it will present new, preclinical data on the efficacy of its ZB131 drug in cholangiocarcinoma (CCA) models at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2022 (Press release, ZielBio, APR 12, 2022, View Source [SID1234612105]). The conference will take place April 8-13, 2022 in New Orleans and virtually. Dr. Lindsey Brinton, Head of Discovery at ZielBio, will present the data in a talk on Tuesday, April 12 at 3:05 in La Nouvelle Orleans C.

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The new preclinical research suggests that ZB131 is effective as a monotherapy in the treatment of CCA, a form of cancer which develops in the bile ducts. When used as a combination therapy with the standard-of-care chemotherapy drug, gemcitabine, ZB131 enhanced the chemotherapy’s anti-tumor effects.

CCA is a cancer with a high unmet need and a survival rate of <20% five years post-diagnosis. Most non-palliative patients relapse within two years and treatments in the advanced setting are limited. CCA tumors are characterized by high expression (>85%) of cancer specific plectin (CSP).

CSP is a pro-tumorigenic protein exclusively expressed on the surface of cancer cells. The common presence of CSP on the surface of CCA cells suggests that anti-CSP therapy may be effective in treating this form of cancer. ZB131 is a first-in-class humanized monoclonal antibody with a high affinity to and specificity for CSP.

In this study, ZB131 was administered as a monotherapy to mice inoculated with human CCA cells (CCA-xenografted mice). ZB131 significantly suppressed tumor growth in the majority of mice, and caused complete regression in 17% of mice. In another group of CCA-xenografted mice, ZB131 was administered in combination with the chemotherapy drug gemcitabine (100 mg/kg). In this group, ZB131 showed an increased tumor response (91% suppression) when compared to gemcitabine alone (74% suppression).

"These findings further confirm that ZB131, currently in Phase 1 clinical trials, presents an exciting possibility for the treatment of CCA and other CSP-positive cancers," said Dr. Kimberly Kelly, CEO of ZielBio. "ZB131 has shown strong antitumor activity in vitro and in mouse models. Additionally, it has demonstrated an excellent safety profile with no toxicities identified in GLP-enabling toxicology studies in non-human primates. We are eager to present these data with the AACR (Free AACR Whitepaper) community and to see what new data arises from our current Phase 1 clinical trial of ZB131."