On January 24, 2022 Patrys reported the completion of the first engineering run for its lead asset PAT-DX1 (Press release, Patrys, JAN 24, 2022, View Source [SID1234606695]).

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The purification of PAT-DX1 from the cell harvest resulted in lower drug product recoveries than expected. Our team is now working with the Contract Development Manufacturing Organisation (CDMO) to implement improvements to the large-scale purification process.

This will mean an extension of the anticipated timeline to start our first in human study for PAT-DX1.

On January 23, 2022 Panbela Therapeutics, Inc. (Nasdaq: PBLA), a clinical stage biopharmaceutical company developing disruptive therapeutics for the treatment of patients with cancer reported the presentation of interim clinical data from its Phase 1b combination therapy study of SBP-101, a proprietary polyamine analogue, with gemcitabine and nab-paclitaxel in patients with metastatic pancreatic ductal adenocarcinoma (PDA), at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal (GI) Meeting that took place January 20-22, 2022 (Press release, Panbela Therapeutics, JAN 23, 2022, View Source [SID1234606716]).

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Jennifer K. Simpson, PhD, MSN, CRNP President & Chief Executive Officer of Panbela Therapeutics, commented, "We are excited to share interim data from cohort 4 and the expansion. A median overall survival (OS) of 12.0 months which is not yet final, and an objective response rate (ORR) of 48%, both exceeded historical rates reported for gemcitabine + nab paclitaxel and supports the continued development of SBP-101 as an addition to first-line treatment for advanced PDA and as neo-adjuvant treatment for patients with potentially resectable disease."

"The conclusion of the abstract is that SBP-101 may enhance first-line treatment with gemcitabine and nab-paclitaxel patients with metastatic PDA. We are encouraged by this conclusion even under sub-optimal conditions, including dose interruptions, which confounded results. Cohorts 2 and 3 did not have the dose interruptions that cohort 4 had, and cohort 2 had an objective response rate of 71%," continued Dr. Simpson. "We intend to continue development of SBP-101 and look forward to executing our global randomized phase 2 study in metastatic PDA."

At the Phase 1b dose and schedule (N=30), CA19-9 levels decreased 60-99% in 70% of evaluable patients, with 1/29 (3%) achieving a complete remission, 13/29 evaluable patients achieving partial responses (45%) and 10/29 achieving stable disease at 8 weeks (34%). PFS was 6.0 months. While PFS may be confounded by SBP-101 dosing holds implemented to investigate potential toxicity, the rates for 6-month PFS was 52% and for 12 month PFS was 10%. Nine subjects are in survival follow up as of the date the poster was presented at the ASCO (Free ASCO Whitepaper) GI meeting. Median OS is 12.0 months and is not final.

The safety population includes all subjects who received at least one dose of SBP-101 (N=50). The most common Grade ≥3 adverse events (AEs) related to any study medication were neutropenia in 20 subjects (19 attributed to G+A and 1 attributed to all 3) and elevated liver function tests in 14 subjects (5 attributed to SBP-101 and 9 attributed to all 3). SBP-101-related increases in LFTs were asymptomatic in all but 2 subjects and reversed in all subjects when SBP-101 administration was interrupted and dose-reduced or discontinued. Additionally, seven subjects experienced serious vision adverse events (4 possibly related to SBP-101, 1 related to gemcitabine and 2 related to all 3 based on PI assessment). All were considered by the sponsor to be possibly related to SBP-101; 5 had findings consistent with retinopathy.

The company has just begun a randomized trial to study SBP-101, as an addition to first-line treatment for metastatic PDA, will begin a neoadjuvant pancreatic trial this quarter and will begin an Ovarian Cancer program mid-year.

Additional meeting information can be found on the ASCO (Free ASCO Whitepaper) website at View Source . After presenting at ASCO (Free ASCO Whitepaper) GI, the poster will be available on the company’s website on January 24, 2022.

About SBP-101
SBP-101 is a proprietary polyamine analogue designed to induce polyamine metabolic inhibition (PMI) by exploiting an observed high affinity of the compound for pancreatic ductal adenocarcinoma and other tumors. The molecule has shown potential signals of tumor growth inhibition in clinical studies of US and Australian metastatic pancreatic cancer patients, suggesting potential complementary activity with an existing FDA-approved standard chemotherapy regimen, if SPB-101 receives approval in the US. In data evaluated from clinical studies to date, SBP-101 has not shown exacerbation of bone marrow suppression and peripheral neuropathy, which can be chemotherapy-related adverse events. Serious visual adverse events observed in the Company’s recently completed Phase 1a/1b clinical trial have been evaluated and patients with a history of retinopathy or at risk of retinal detachment will be excluded from future SBP-101 studies. The safety data and PMI profile observed in the current Panbela sponsored clinical trial provides support for continued evaluation of SBP-101 in a randomized clinical trial. For more information, please visit View Source .

On January 23, 2022 Ascletis Pharma Inc. (HKEX code: 1672) reported the dosing of the first patient in the Phase III registration clinical trial of ASC40 combined with bevacizumab for treatment of recurrent glioblastoma (rGBM) (Press release, Ascletis, JAN 23, 2022, View Source [SID1234606700]). ASC40 is an oral, selective inhibitor of fatty acid synthase (FASN), a key enzyme which regulates de novo lipogenesis (DNL) . ASC40 inhibits energy supply and disturbs membrane phospholipid composition of tumor cells by blocking de novo lipogenesis.

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The Phase III registration study (ClinicalTrials.gov Identifier: NCT05118776) is a randomized, double-blind, placebo-controlled, multi-center clinical trial in China to evaluate progression-free survival (PFS), overall survival (OS) and safety of patients with rGBM. Approximately 180 patients will be 1:1 randomized to Cohort 1 (oral ASC40 tablet once daily + Bevacizumab) and Cohort 2 (matching placebo tablet once daily + Bevacizumab). Approximately 80% of such 180 patients with rGBM in the Phase III clinical trial are expected to be randomized and enrolled by the end of December 2022.

The Phase II study, completed in the U.S., in patients with rGBM has shown that the objective response rate (ORR) for ASC40 plus Bevacizumab treatment was 65% including a complete response (CR) of 20% and a partial response (PR) of 45%.

Based on published data, in China, glioblastoma (GBM) represents 57% of gliomas and has an incidence rate of approximately 2.85 to 4.56 per 100,000 population per year, suggesting approximately 40,000 to 64,000 new cases of GBM per year. More than 90% GBM patients will relapse after surgery, radiation and chemotherapies. In the U.S., GBM represents 56.6% of gliomas and has an incidence rate of approximately 3.21 per 100,000 population per year.

"I am pleased that the first patient has been successfully dosed in the Phase III clinical trial of ASC40 combined with bevacizumab for treatment of recurrent glioblastoma. As the first clinical trial targeting tumor lipid metabolism in China, we are looking forward to the results of the trial," said Dr. Wenbin Li, Vice Chairman and Secretary General of Glioma Committee of Chinese Cancer Association, Director of the Comprehensive Tumor Treatment Center, Beijing Tiantan Hospital, Capital Medical University.

"Dosing the first patient in ASC40 Phase III registration study is a significant milestone for our oncology pipeline. We are looking forward to the data from this Phase III study," said Dr. Jinzi J. Wu, Founder, Chairman and CEO of Ascletis.

In Ascletis’ oncology pipeline, in addition to FASN inhibitors, there are two oral PD-L1 small molecule inhibitors developed in-house, namely ASC61 and ASC63. Ascletis has filed a U.S. Investigational New Drug (IND) application of ASC61 for the treatment of advanced solid tumors.

On January 23, 2022 Applied Pharmaceutical Science, Inc. ("APS" or "the Company"), reported the Investigational New Drug (IND) application for its self-developed breakthrough new drug APS03118, a next generation selective RET inhibitor, has been approved by the U.S. Food and Drug Administration (FDA) (Press release, Applied Pharmaceutical Science, JAN 23, 2022, View Source [SID1234606699]). The clinical application is also in the process of being submitted to the National Medical Products Administration (NMPA) in China, and a global multi-center clinical trial is in the pipeline for initiation in the second quarter of 2022 in the U.S., China and Australia etc.

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APS03118 is a novel innovative drug developed by APS with global independent intellectual property rights for unlimited cancer types, targeting patients with non-small cell lung cancer, thyroid cancer, pancreatic cancer, breast cancer, ovarian cancer, colorectal cancer and other advanced solid tumors caused by rearranged during transfection (RET) gene alterations, as well as patients with resistance to first-generation selective RET inhibitors. The currently marketed first-generation selective RET inhibitors have both been granted priority review, breakthrough therapy, orphan drug status, accelerated approval and other review incentives by the FDA for their impressive efficacy.

Preclinical studies have shown that APS03118 is highly selective for RET kinases, and compared to the currently marketed first-generation selective RET inhibitors APS03118 showed significant nanomolar level potent antitumor activity in inhibition to various RET fusion and mutations including RET gatekeeper V804M/L/E and solvent frontier G810R/S/C mutations which lead to resistance to selective RET inhibitors. APS03118 also exhibited potent antitumor activity with a good safety profile in mouse models, and more significantly, in a brain tumor model, APS03118 completely eliminated brain tumors and all animals survived after dosing, demonstrating the therapeutic advantages of APS03118 for patients with brain metastases. It is potentially the best selective RET inhibitor of its kind globally.

Dr. Jun Zhong, Vice President of R&D at APS, said, "We are delighted that APS03118 has been clinically approved in the U.S. for a global unmet clinical need and that our self-developed innovative drug has been recognized by the FDA. APS has always adhered to its international development strategy to provide a new generation of precision therapeutic solutions for cancer patients worldwide."

On January 22, 2022 Natera, Inc. (NASDAQ: NTRA), a leader in personalized genetic testing and diagnostics, reported that new data recently presented on the clinical utility of Signatera, its personalized and tumor-informed molecular residual disease (MRD) test, at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper)’s 2022 Gastrointestinal Cancers Symposium (ASCO GI) (Press release, Natera, JAN 22, 2022, View Source [SID1234606701]). The oral presentation included an updated analysis from the landmark CIRCULATE-Japan trial analyzing a cohort of colorectal cancer (CRC) patients.

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More than 3,000 CRC patients are now enrolled in CIRCULATE-Japan, the largest prospective, multi-center, MRD-guided trial in CRC, using Signatera to monitor MRD status in patients with stage I-IV CRC up to 96 weeks post-surgery. The latest analysis of more than 1,000 patients from the observational GALAXY arm of the study highlighted three novel findings that were presented at the conference:

Signatera positivity is predictive of treatment benefit: patients who were MRD-positive at 4 weeks post-op benefited significantly from adjuvant chemotherapy (ACT), across all stages of disease.
Signatera-negative patients did not benefit from ACT: patients with high-risk stage II and stage III disease who were MRD-negative at 4 weeks post-op did not derive significant benefit from ACT (p-value of .63).
Signatera dynamics during ACT is predictive of treatment benefit: 68% of ACT-treated patients cumulatively cleared their ctDNA by week 24 and had significantly better outcomes relative to those who remained ctDNA-positive, with a hazard ratio of 15.8.
In addition, the single time point post-surgical sensitivity of Signatera in stage II and III CRC was 67.6%. This sensitivity analysis included over 5 times more cancer recurrences than previously reported in Reinert, et. al.1

"Definitive evidence has now been presented that personalized MRD testing can guide adjuvant treatment decisions, particularly for MRD-positive patients who clearly benefit from adjuvant chemotherapy," said the CIRCULATE-Japan study’s principal investigator, Dr. Takayuki Yoshino, of the National Cancer Center Hospital East, Kashiwa, Chiba, Japan. "We see these results as an important step forward in establishing MRD-guided adjuvant therapy as the standard of care for colorectal cancer patients worldwide."

"Current guidelines recommend combination chemotherapy for all patients with stage III CRC, yet it is known that up to 40% are cured by surgery alone. Our study demonstrates that MRD testing can help stratify and predict which patients are likely to benefit from systemic therapy," said Alexey Aleshin, M.D., VP of oncology medical affairs at Natera. "We are extremely pleased with these groundbreaking results from CIRCULATE-Japan and are optimistic they may change practice guidelines."

The full presentation, as shown at ASCO (Free ASCO Whitepaper) GI, is available here.

About Signatera

Signatera is a custom-built circulating tumor DNA (ctDNA) test for treatment monitoring and molecular residual disease (MRD) assessment in patients previously diagnosed with cancer. The test is available for both clinical and research use, and has been granted three Breakthrough Device Designations by the FDA for multiple cancer types and indications. The Signatera test is personalized and tumor-informed, providing each individual with a customized blood test tailored to fit the unique signature of clonal mutations found in that individual’s tumor. This maximizes Signatera’s accuracy for detecting the presence or absence of residual disease in a blood sample, even at levels down to a single tumor molecule in a tube of blood. Signatera is intended to detect and assess how much cancer is left in the body, to identify recurrence earlier and to help optimize treatment decisions.