On September 5, 2022 CellOrigin Biotech (Hangzhou) Co., Ltd. reported that it has made an agreement with Qilu Pharmaceutical on strategic global collaborations to develop, manufacture and commercialize a proprietary ‘off-the-shelf’ iPSC-derived Chimeric Antigen Receptor Macrophages (CAR-iMAC) for cancer immnotherapy (Press release, Qilu Pharmaceutical, SEP 5, 2022, View Source [SID1234619124]).

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This collaboration takes the advantages from both parties by integrating complementary technologies and expertise as well as combining industry-leading R&D, manufacture and marketing capabilities.Both parties will collaborate on new drug development and commercialization, and will push CAR-iMAC pipelines forward to clinical trials.

‘Innovation, and bringing the best products to benefit patients are the core values we both appreciate’, said Dr. Jin Zhang, the co-founder of CellOrigin Biotech and a principle investigator of Zhejiang University, ‘that’s something that brings us together’.

‘We are excited to collaborate with Qilu Pharmaceutical because of its prestige in the Chinese pharmaceutical industry as well as its successful track record in new drug discovery. We (CellOrigin) will keep seeking other potential industry collaborators, jointly exploring and developing innovative anti-tumor drugs, and benefiting more cancer patients’ said Dr. Tong Jiansong, Chief Executive Office at CellOrigin Biotech.

‘CellOrigin is an outstanding startup with a strong research background and valuable industry experience. It has focused on original techniques in cell therapy and gained rich expertise in GMP manufacture. It is an ideal strategic partner for novel cell therapy and it is our pleasure to collaborate with such a great biotech company.’ said Qilu Pharmaceutical.

On September 5, 2022 Dizal reported positive topline results from the first pivotal study of sunvozertinib (DZD9008) in platinum-pretreated NSCLC Patients with EGFR exon20ins mutations at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Annual Meeting (Press release, Dizal Pharma, SEP 5, 2022, View Source [SID1234619001]). The trial met the primary endpoint, cORR, as assessed by Blinded Independent Central Review (BICR).

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Even though lung cancer is the second most common cancer and leading cause of cancer death globally, NSCLC patients with EGFR exon20ins mutation lack effective treatment options, especially those who develop brain metastases (BM) historically have worse outcomes. Sunvozertinib (DZD9008), which was granted Breakthrough Therapy Designation by both the US FDA and China CDE, is a rationally designed, oral, potent EGFR exon20ins inhibitor, with wild-type EGFR selectivity.

The topline result presented at 2022 ESMO (Free ESMO Whitepaper) was based on the latest data from WU-KONG6 study, the multicenter, single-arm, Phase II pivotal study conducted in China. As of 31 July 2022, the efficacy set included 97 platinum-pretreated NSCLC patients with EGFR exon20ins mutations. Key findings from efficacy set are as follows:

Parameter

Results in 300 mg cohort (N=97)

Confirmed ORR per BICR

59.8% (58/97)

Confirmed ORR in patients with baseline brain
metastasis per BICR

48.4% (15/31)

*Patients are still on treatment and responding.

Sunvozertinib also demonstrated a favorable safety profile. Of all 277 patients in the safety set, the most common treatment-related adverse events (TEAE) were diarrhea and rash, the majority of which were Grade 1/2 and clinically manageable.

"The importance of advancing research on NSCLC with EGFR exon20ins mutation – a complicated and devastating disease – cannot be overstated, as available treatment options provide limited benefit especially to those develop brain metastasis," said Dr. Xiaolin Zhang, CEO of Dizal, "It is great news to our patients that sunvozertinib is showing such strong antitumor activities with a benign safety profile. This data further strengthens our confidence in sunvozertinib and reinforces its best-in-class position"

About sunvozertinib (DZD9008)

Sunvozertinib was designed with the goal to address the limitations of existing NSCLC therapies. It is an irreversible inhibitor targeting EGFR exon 20 insertion mutations as well as EGFR sensitizing T790M and uncommon mutations while maintaining selectivity against wild-type EGFR. The first pivotal study WU-KONG6 of sunvozertinib has achieved its primary endpoint, demonstrating superior antitumor efficacy in pre-treated NSCLC patients with EGFR exon20 insertion mutations. The confirmed ORR (cORR) at 300 mg was 59.8% by BICR. Patients with baseline brain metastasis showed significant response as well, with a confirmed ORR of 48.4%. (Data cut-off date: July 31, 2022). It is well tolerated with a manageable AE profile. Global pivotal studies are ongoing for ≥ 2nd line and 1st line treatment of NSCLC with EGFR exon20 insertion mutation in countries including China, U.S., EU, Australia, South Korea and other countries and regions.

About EGFR Exon20ins

Lung cancer is the leading cause of cancer death in the world. It is classified broadly as non-small cell lung cancer (NSCLC), accounting for 85% lung cancer cases, and small cell lung cancer (SCLC). EGFR mutation is common in NSCLC. About 4–12% of all EGFR mutations are insertions at exon 20 (EGFR exon20ins). Patients with EGFR exon20ins generally don’t respond to the first-, second- and third-generation EGFR tyrosine kinase inhibitors (TKIs).

On September 5, 2022 OSE Immunotherapeutics SA (ISIN: FR0012127173; Mnemo: OSE) reported the presentation of two new analyses from the Phase 3 Atalante-1 study of immunotherapy Tedopi, in patients with advanced non-small cell lung cancer (NSCLC) in secondary resistance after failure of previous checkpoint inhibitor treatments, at the 2022 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress, being held September 9-13, in Paris (Press release, OSE Immunotherapeutics, SEP 5, 2022, View Source [SID1234646962]).

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Alexis Vandier, Chief Executive Officer of OSE Immunotherapeutics, commented: "In patients with no treatment option after failure of two therapeutic classes, in particular post-checkpoint inhibitors, Tedopi has shown an overall clinical benefit in this phase 3 study, integrating both efficacy and tolerance compared to chemotherapy treatments. This new specific immunotherapy offers prospects for therapeutic management, both in monotherapy and in combination, and we will do our best to make this treatment available as soon as possible for these patients."

The first analysis compared Tedopi to the Standard of Care (SoC) in patients with advanced NSCLC after secondary resistance to sequential use of chemotherapy followed by immunotherapy (CT-IO).

The results have shown that in advanced HLA-A2+ NSCLC patients with IO secondary resistance after sequential CT-IO (n=118), overall survival (OS) was longer with Tedopi versus SoC regardless of the use (or not) of post progression anticancer treatment (with 13.5 months versus 10.6, HR=0.71; without 6.3 months versus 4.5, HR=0.76).

This analysis will be presented by Dr Maria Rosario Garcia Campelo (Head of Medical Oncology Department, Thoracic Tumors Unit, Investigator of Atalante-1 study, University Hospital A Coruña, Spain).

Dr Garcia Campelo said: "There is a strong medical need for a new therapeutic alternative in these heavily pretreated NSCLC patients, aiming not only at a prolonged survival but desiring a maintained global health status."

The second analysis assessed the overall benefit/risk of Tedopi versus SoC chemotherapy in patients with NSCLC who failed therapy with immune checkpoint inhibitors. The Net Treatment Benefit (NTB)*, a new statistical method combining efficacy, safety and quality of life, was assessed in the overall population (n=219). NTB of Tedopi was of 19% and reached statistical significance (p=0.035).

This analysis will be presented by Dr Marc Buyse, (Founder and Chief Scientific Officer, International Drug Development Institute (IDDI), Brussels, Belgium).

Poster presentation details:
Title: Pattern of clinical activity of anticancer vaccine OSE2101 in HLA-A2+ non-small cell lung cancer (NSCLC) patients after failure to immune checkpoint inhibitors (IO) in Phase 3 Atalante-1 randomized trial
Presentation Number: 1019P
Speaker: Maria Rosario Garcia Campelo (A Coruña, Spain)
Date: Monday, September 12th, 2022

Title: Net Treatment Benefit of OSE2101 in HLA-A2+ non-small cell lung cancer (NSCLC) patients after failure to immune checkpoint inhibitors (IO) in Phase 3 Atalante-1 randomized trial
Presentation Number: 1024P
Speaker: Marc E. Buyse (Louvain-la-Neuve, Ottignies, Belgium)
Date: Monday, September 12th, 2022

On September 5, 2022 Several academic centers have collaborated with Convert Pharmaceuticals to expand knowledge about its main compound, CP-506, and the biomarkers that will enable selection of patients that would most benefit from the hypoxia activated prodrug under investigation (Press release, Convert Pharmaceuticals, SEP 5, 2022, View Source [SID1234618984]). These research efforts have recently led to three key peer-reviewed academic publications which are referenced here-under.

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The results from the first paper1, published in 2021, demonstrate that CP-506 selectively targets hypoxic tumor cells and has broad antitumor activity.

The second paper2, published in 2022, focusses on the in vivo identification of Adducts from CP-506. The resulting in vitro data suggests that the structural changes performed on CP-506 improved the drug selectivity toward hypoxic conditions compared to its predecessor PR-104, as shown by more adducts being detected in anoxic versus normoxic treatment, but did not completely eliminate its ability to react directly with DNA enabling a bystander-effect.

This favorable bystander efficiency of the new generation pro-drug has been further studied using in silico spatially-resolved pharmacokinetic/pharmacodynamic (SR-PK/PD) modelling and spheroid co-cultures for validation. The results of this study, demonstrating the favourable pharmacological properties of CP-506 in tumour tissue, have been published in a third recently published paper3.

On September 5, 2022 Dizal reported the promising safety and pharmacokinetic data from the global Phase I study of DZD1516 in patients with HER2 positive metastatic breast cancer (HER2+ MBC) who relapsed from multiple prior treatments at the 2022 European Society for Medical Oncology Annual Meeting (Press release, Dizal Pharma, SEP 5, 2022, View Source [SID1234619002]).

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Nearly 60% of patients with advanced HER2-positive breast cancer develop brain metastasis and the prognosis is extremely poor. DZD1516 is an oral, full blood-brain barrier (BBB) penetrant selective HER2 inhibitor for the treatment of HER2-positive metastatic breast cancer.

The Phase I study is enrolling HER2+ MBC patients who relapsed from or were intolerant to the standard of care (SoC). The primary objective is to evaluate the safety of DZD1516 and to define maximum tolerated dose (MTD). As of February 20, 2022, DZD1516 was explored in 22 HER2+ MBC patients from the USA and China, among whom nearly 70% had CNS metastases at baseline. Key findings are as follows:

DZD1516 was well tolerated at doses ≤ 250 mg, and in consistent with its high selectivity, no wild-type EGFR-related AEs have been reported. Thus, 250 mg was defined as MTD.
In patients, mean Kpuu,CSF was 2.1 for DZD1516 across the dose range, indicating full penetration of DZD1516 through human BBB.
18 patients had completed ≥ 1 post treatment RECIST assessment. With a median of 7 lines of prior systemic treatment (86% treated with HER2 TKI), the best antitumor efficacy in intracranial, extracranial and overall lesions was stable disease.
"Patients with HER2 positive breast cancer and brain metastasis have poor outcomes due to the limited therapies," said Dr. Xiaolin Zhang, CEO of Dizal, "Based on these promising findings, we will further explore the potential of DZD1516 as a new treatment option for this underserved patient population."

About 1516

DZD1516 is designed as an oral, potent, reversible, highly selective, and full blood-brain barrier (BBB) penetrant HER2 tyrosine kinase inhibitor (TKI), with more than 300-fold selectivity for HER2 compared to wild-type EGFR. It is well tolerated at doses ≤ 250 mg, twice daily. And in consistent with its high selectivity, no wild-type EGFR-related AEs have been reported. In patients, mean Kpuu,CSF is 2.1 for DZD1516 across the dose range, indicating full penetration of DZD1516 through human BBB.