On April 11, 2022 Shanghai Henlius Biotech, Inc. (2696.HK) reported that the New Drug Application (NDA) of HANSIZHUANG (serplulimab), a novel anti-PD-1 monoclonal antibody (mAb) independently developed by the company, in combination with chemotherapy for the first-line treatment of extensive stage small cell lung cancer (ES-SCLC) has been accepted by the National Medical Products Administration (NMPA). Henlius also plans to file MAA in the EU in 2022 (Press release, Shanghai Henlius Biotech, APR 11, 2022, View Source [SID1234612010]). There’s no PD-1 has been approved globally for first-line treatment of SCLC up to date and HANSIZHUANG potentially the world’s first PD-1 inhibitor for the first-line treatment of SCLC.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Professor Ying Cheng, the principal investigator of the study, Director of Jilin Department of Medical Oncology Cancer Center, Jilin Province Lung Cancer Diagnosis and Treatment Center, and Jilin Cancer Hospital Malignant Tumor Clinical Research Integrated Diagnosis and Treatment Center, said, "ASTRUM-005 is the first and largest ES-SCLC international multi-center clinical study led by Chinese researchers for anti-PD-1 mAb. The favorable clinical results demonstrated that the predefined primary study endpoint had been reached, providing evidence of safety and efficacy. We are hoping that the approval of HANSIZHUANG for the treatment of ES-SCLC comes soon to mend the gap and bring a new treatment option to patients living with ES-SCLC. "

Mr. Jason Zhu, President of Henlius, said, "HANSIZHUANG is an innovative mAb independently developed by Henlius, and SCLC is the third indication for which the NDA has been accepted by NMPA and Orphan-Drug Designation has been recently granted by the United States Food and Drug Administration (FDA). Based on the large number of unmet clinical needs as well as the intractable cancers both globally and in China, the company has implemented a comprehensive first-line treatment strategy for lung cancer with multiple multi-center Phase 3 clinical trials. Going forward, we will proactively promote the combination immunotherapy of HANSIZHUANG and clinical research, thereby benefiting more patients in China and around the world."

HANSIZHUANG significantly improves the overall survival and fill the gap in demand for patients with SCLC

Small cell lung cancer (SCLC) accounts for 15%–20% of all cases and is the most aggressive type of lung cancer (LC). It is classified into two stages: limited stage (LS-SCLC) and ES-SCLC, with both exhibiting high malignancy, strong invasiveness, early metastasis, fast disease progression, and a poor prognosis. At present, anti-PD-L1 mAb combined with chemotherapy has been recommended by the latest NCCN guidelines and CSCO guidelines as the first-line treatment for ES-SCLC. In recent years, however, a number of PD-1 mAbs have failed in the area.

The NDA is based on the results from a randomised, double-blind, international, multi-centre, phase 3 clinical study (ASTRUM-005) that aims to compare the efficacy and safety of HANSIZHUANG with placebo when combined with chemotherapy (carboplatin-etoposide) in previously untreated patients with ES-SCLC. This study has set up about 128 sites in China, Turkey, Poland, Georgia, etc. and 585 subjects were enrolled, among whom 31.5% were Caucasian. In December 2021, ASTRUM-005 had met its primary study endpoint of the overall survival (OS) in the interim analysis results. The study results demonstrated that HANSIZHUANG can significantly extend the OS to 15.38 months for the group of HANSIZHUANG, reducing risk of death by 38% (41% in the Asian subgroup) a manageable safety profile. The global clinical data lays a solid foundation for future applications across the world.

China has the highest incidence of LC, and HANSIZHUANG is intended as a first-line treatment option for all subtypes of LC

According to GLOBOCAN 2020, LC is the second most common cancer around the world. There were 2.2 million new LC cases worldwide, with China accounting for 0.8 million new LC cases. Moreover, with 1.8 million new deaths in 2020, LC is the leading cause of cancer deaths worldwide. Non-small cell lung cancer (NSCLC) accounts for about 85% among LC, with squamous non-small cell lung cancer (sqNSCLC) accounting for about 30%. Most lung cancer patients are diagnosed at an advanced stage and lack the opportunity for surgical resection. The advent of immune checkpoint inhibitors has been proved to bring hope to patients with LC.

Henlius has carried out a comprehensive first-line immune-oncology treatment layout for LC in sqNSCLC, non-squamous non-small cell lung cancer (nsNSCLC), ES-SCLC, and LS-SCLC. For NSCLC, the company has conducted a randomised, double-blind, global multi-centre Phase 3 clinical trial in patients with locally advanced or metastatic sqNSCLC patients to compare HANSIZHUANG in combination with chemotherapy versus chemotherapy in respect of efficacy and safety. The NDA was accepted as a result of the study meeting the primary endpoints. Also, a study to explore dual mAbs combination therapy of HANSIZHUANG and HANBEITAI (bevacizumab) for the first-line treatment of nsNSCLC has entered the pivotal Phase 3 stage. For SCLC, on the other hand, the investigational new drug application (IND) of international multicenter phase 3 studies of HANSIZHUANG in patients with LS-SCLC has been approved by NMPA in addition to ASTRUM-005 for the treatment of ES-SCLC. Notably, FDA has granted Orphan-Drug Designation for HANSIZHUANG for the treatment of SCLC, benefiting the continuous development of HANSIZHUANG and the enjoyment of certain policy support in terms of registration and commercialization in the United States.

In the future, the company will continue to emphasize unmet clinical needs and actively promote the combination immunotherapy of HANSIZHUANG and international regulatory registration to benefit more patients around the world.

About HANSIZHUANG

HANSIZHUANG (recombinant humanized anti-PD-1 monoclonal antibody injection, generic name: serplulimab injection) is the first innovative monoclonal antibody developed by Henlius. It is approved by the NMPA for the treatment of MSI-H solid tumors in March 2022. Henlius actively promotes HANSIZHUANG in conjunction with in-house products of the company and innovative therapies. It has successively obtained clinical trial licenses in China, the United States, the European Union and other countries and regions to initiate 9 clinical trials on immuno-oncology combination therapies of HANSIZHUANG worldwide in a wide variety of indications, such as lung cancer, esophageal carcinoma, head and neck squamous cell carcinoma and gastric cancer, etc., and covering the full range of first-line treatments of lung cancers. Up to date, the company has enrolled more than 2,800 subjects in China, Turkey, Poland, Georgia and other countries and regions, and the proportion of Caucasian is over 30% in two MRCTs, making HANSIZHUANG an anti-PD-1 mAb with one of the largest global clinical data pools. The NDA of the treatment for squamous non-small cell lung cancer (sqNSCLC) has been accepted by the NMPA and is expected to be approved in 2022. Furthermore, the global multi-center phase 3 clinical study of HANSIZHUANG in combination with chemotherapy in previously untreated extensive small-cell lung cancer (ES-SCLC) met the primary endpoint of overall survival (OS) with remarkable readouts. Its NDA in China has been accepted by the NMPA and MAA in the EU are expected to be filed in 2022, making this product potentially the world’s first anti-PD-1 mAb for the first-line treatment of SCLC.

On April 11, 2022 Freenome, a privately held biotech company, reported that it will present research at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting that measures the clinical impact of detecting precancerous adenomas for tests that screen for colorectal cancer (CRC), including multi-cancer early detection (MCED) tests (Press release, Freenome, APR 11, 2022, View Source [SID1234612009]). The research modeled detecting adenomas and cancer (prevention and interception) or primarily cancer alone (interception) for such tests.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The research found that even modest improvements in detecting adenomas resulted in more favorable CRC clinical outcomes than detecting primarily cancer alone. Since different cancers have different preclinical phases, the clinical utility of detecting precancerous lesions varies accordingly.[1] In CRC, detection and removal of adenomas and early-stage CRC significantly reduces CRC incidence and mortality.[2]

Using Freenome’s validated model, CRC-MAPS, researchers simulated adherence to an annual, blood-based CRC screening test among average-risk adults aged 45-75. Four scenarios were modeled:

A cancer interception test with clinical performance comparable to or better than that reported for some MCED tests3,4
A cancer interception test with near-perfect performance
Two cancer prevention and interception scenarios with varying adenoma sensitivity
A threshold analysis was also performed to determine the ≥10mm adenoma sensitivity needed for a cancer prevention and interception test to result in the same CRC mortality reduction as a near-perfect cancer interception test.

The results demonstrated that the cancer prevention and interception scenarios resulted in outcomes 2.3 to 5.6 times more favorable than the cancer interception scenarios due to increased adenoma detection. Further, the threshold analysis found that increasing the ≥10mm adenoma sensitivity by less than one (1) percentage point, from 1% to 1.94%, resulted in the same reduction in CRC mortality as the near-perfect interception test.

"This study shows the clinical impact of detecting adenomas in any test that screens for CRC," said Girish Putcha, M.D., PhD., lead author of the study and senior vice president, Freenome. "This is just one example of how clinical performance requirements vary by cancer, and why it’s important to consider each cancer separately when it comes to helping patients and improving health outcomes."

On April 11, 2022 Debiopharm, (www.debiopharm.com/debiopharm-international/) an oncology and infectious disease focused biopharmaceutical company based in Switzerland, reported data releases on 3 investigational products including Debio 0123 (Selective WEE1 inhibitor), clinical exploratory results for xevinapant (IAP inhibitor), and 2 Multilink technology posters (antibody drug conjugate linker) at the 2022 Annual American Association for Cancer Research (AACR) (Free AACR Whitepaper) meeting in New Orleans, Louisiana (Press release, Debiopharm, APR 11, 2022, View Source [SID1234612008]). The AACR (Free AACR Whitepaper) conference serves as the focal point of the cancer research community to gather together and share advances in oncology science. Debiopharm and their partners’ poster presentations represent scientific progress in the research of these compounds leveraging novel modes of action and new delivery methods in development to treat cancer types with high unmet needs.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Scientific cancer research is evolving quickly, bringing us the insights needed to better develop safer and more effective anti-tumor therapies. Our ultimate vision is to translate these findings into meaningful outcomes for patients in future clinical settings," explained Carolina Haefliger, Head of Translational Medicine at Debiopharm.

AACR 2022 Poster Sessions

Compound

Title

Date and Time

N°

Debio 0123

The WEE1 inhibitor Debio 0123
enhances the efficacy of standard
of care DNA Damaging agents in
lung cancer models

Tue, April 12th,
9:00am-12:30pm

Section 5

#4894

Multilink technology

A novel antibody drug conjugate
linker enabling production of ADCs
with high drug to antibody ratios
and fast payload release for improved efficacy

Mon, April 11th,
1:30-5:00pm

Section 21

#4882

Multilink technology
(combined with Genome & Co’s Antibody)

The antibody-drug conjugate GENA-111
conjugated to auristatin F shows
therapeutic potency in BCAM positive epithelial cancer

Mon, April 11th,
1:30-5:00pm

Section 21

#1716

xevinapant
(rights under Merck KGaA, Darmstadt, Germany)

The IAP antagonist xevinapant in combination
with high-dose cisplatin chemoradiotherapy
induces NF-kB and apoptotic pathway biomarkers
in patients with high-risk, locally advanced
squamous cell carcinoma of the head and neck

Tue, April 12th,

1:30-5:00pm

Section 33

#603

About Debio 0123
Debio 0123 is an inhibitor of WEE1 kinase, a key regulator of the G2/M and S phase checkpoints, activated in response to DNA damage, allowing cells to repair their DNA before resuming their cell cycle. WEE1 inhibition, particularly in combination with DNA damaging agents, induces DNA breaks leading to the accumulation of DNA damage. In conjunction with abrogation of other checkpoints such as those of the G1 phase of the cell cycle, the compound pushes the cells through cycle without DNA repair, promoting mitotic catastrophe and inducing apoptosis of cancer cells.

About Multilink
Multilink is a new cleavable linker platform suited for multidrug attachment and compatible with any conjugation technology to produce ADCs with high DAR (drug-to-antibody ratio), allowing the loading of multiple payloads on an antibody for an enhanced therapeutic effect. This highly effective and well-tolerated linker platform is available for use of other specialty biotech or pharmaceutical companies to generate a proprietary, clinical-stage ADCs.

About xevinapant
Xevinapant, now exclusively licensed to Merck for product development and commercialization, is a potential first-in-class potent, oral, small-molecule inhibitor of IAPs (Inhibitor of Apoptosis Proteins). In preclinical studies, xevinapant restored sensitivity to apoptosis in cancer cells, thereby depriving them of one of their major resistance mechanisms to anticancer therapy. Currently in phase III clinical research, in a randomized, placebo-controlled phase II study, xevinapant has demonstrated preliminary evidence of efficacy in combination with chemoradiotherapy (CRT) in patients with high-risk locally advanced squamous cell carcinoma of the head and neck (LA SCCHN), with a clinically significant and sustained clinical activity and an acceptable safety profile compared with CRT alone.

On April 11, 2022 Kintara Therapeutics, Inc. (NASDAQ: KTRA) ("Kintara" or the "Company"), a biopharmaceutical company focused on the development of new solid tumor cancer therapies, reported that it has presented data at the 2022 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting (Press release, Kintara Therapeutics, APR 11, 2022, View Source [SID1234612007]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Data Presentation:

Track 24: Experimental and Molecular Therapeutics

Session PO.ET02.01 – Mechanisms of Drug Action 1

1843 / 15 – Dianhydrogalactitol (VAL-083) for the Treatment of Glioblastoma Multiforme (GBM): Impact of Glucose Transporters for Crossing the Blood Brain Barrier (BBB)

(Presentation Time: Monday, April 11, 2022 – 1:30 p.m. to 5:00 p.m. CT)

Enhanced drug concentrations of VAL-083 in the brain and GBM brain tumors in comparison to circulating plasma concentrations have been observed in human clinical trials. Most therapeutic agents targeting brain tumors have very limited access to primary brain tumors due to the protective nature of the BBB that limits access for most chemical structures.

VAL-083 shares structural and molecular similarities to glucose including low molecular weight and high water solubility. Glucose transporters, in particular GLUT1, are overexpressed by the BBB since the brain requires very high concentrations of glucose for metabolism. Laboratory studies presented at the meeting assessed whether glucose transporters are involved in the ability of VAL-083 to cross the BBB.

Three glucose transporters were studied in vitro including SGLT1, SGLT2 and GLUT1. For all three transporters VAL-083 was not a substrate for these active transport systems. This suggests that VAL-083 may be crossing the BBB by passive diffusion rather than facilitated active transport.

VAL-083 has some physical chemical parameters that differ from glucose. These include increased lipophilicity (log P) and a significantly lower polar surface area (PSA) (lower surface charge) which may allow for relatively unencumbered passive diffusion across the lipid cell membranes of the BBB as well as GBM tumor cells. This independence for the need for specific active drug transporters may help to explain the enhanced drug concentrations of VAL-083 observed clinically in GBM.

"These results are extremely important," said Dennis Brown, Ph.D., Kintara’s Chief Scientific Officer. "We thought that since there were numerous structural similarities between VAL-083 and glucose that perhaps a specialized glucose transporter could explain the favorable brain concentration demonstrated clinically for VAL-083. It appears that other molecular features like PSA and log P may account for the very unique pharmacologic properties we are observing. This suggests that the clinical pharmacokinetics of VAL-083 would result in less inter- and intra-patient variability in CNS penetration and, therefore, greater precision of drug dosing to the brain.

On April 11, 2022 Linnaeus Therapeutics, Inc. (Linnaeus), a privately held clinical-stage biopharmaceutical company focused on the development and commercialization of novel small-molecule oncology therapeutics, reported that the laboratory of Gary Schwartz, MD at Columbia University Irving Medical Center presented new findings from his research team at the 2022 AACR (Free AACR Whitepaper) Annual Meeting (Press release, Linnaeus Therapeutics, APR 11, 2022, View Source [SID1234612004]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The poster was entitled, "G protein-coupled estrogen receptor-1 agonist LNS8801 induces mitotic arrest and cell death in uveal melanoma cells" and was led by Grazia Ambrosini, PhD, a research scientist in Dr. Schwartz’s lab (Abstract 1852).

Ambrosini and colleagues have demonstrated that LNS8801 has potent anti-cancer activities in models of uveal melanoma cells. Treatment with LNS8801 resulted in inhibition of proliferation and depletion of c-Myc and phospho-RB proteins. The inhibition of proliferation was associated with a G2/M cell cycle block through the disruption of microtuble dynamics and mitotic spindle formation. LNS8801 treatment also resulted in the inhibition of migration and induction of cell death. LNS8801 had potent effects in an in vivo xenograft model of uveal melanoma, resulting in the inhibiton of tumor growth.

"We are extremely pleased to showcase these data at AACR (Free AACR Whitepaper)," commented Patrick Mooney, MD, CEO of Linnaeus. "These data demonstrate that LNS8801 has activity in preclinical models of uveal melanoma in vitro and in vivo. Importantly, these data are consistent with the clinical data in our on-going studies of LNS8801 in advanced cancer patients. We look forward to sharing some of that data at ASCO (Free ASCO Whitepaper) in June."

About LNS8801
LNS8801 is an orally bioavailable and highly specific and potent agonist of GPER whose activity is dependent on the expression of GPER. GPER activation by LNS8801 rapidly and durably depletes c-Myc protein levels. In preclinical cancer models, LNS8801 displays potent antitumor activities across a wide range of tumor types, rapidly shrinking tumors and inducing immune memory.

In the ongoing clinical study in humans, LNS8801 monotherapy has been safe and well tolerated. Additionally, LNS8801 has demonstrated target engagement, c-Myc protein depletion, and clinical benefit in patients with advanced cancer.