On September 14, 2020 PharmAbcine Inc. (KOSDAQ: 208340ks) reported positive data from its two combination trials of olinvacimab, its leading clinical candidate in oncology, with MSD’s pembrolizumab at the 13th Annual Meeting of the Korean Society of Medical Oncology (KSMO 2020) (Press release, PharmAbcine, SEP 14, 2020, View Source [SID1234565132]).

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The interim results from the two Phase Ib studies showed that olinvacimab & pembrolizumab, combo has an excellent safety profile in both recurrent glioblastoma multiforme (rGMB) and metastatic Triple-Negative Breast Cancer (mTNBC) patients. The results from the mTNBC study, in particular, demonstrated meaningful efficacy.

Both rGBM and mTNBC trials assessed dose-limiting toxicity (DLT) and safety, as the primary endpoint to establish a preliminary RP2D (Recommended Phase II Dose). The studies also measured ORR, DCR, PFS, and OS for efficacy as the secondary endpoint.

The data indicates that both combination therapies have an excellent safety profile. DLT, the most crucial factor that determines the safety and dosage, was not observed. In both trials, many patients showed manageable symptoms of fatigue, rash, or hemangioma in grade 1 or 2.

In terms of efficacy, the data from the mTNBC trial was more pronounced. Among 11 patients, 4 patients (36%) had PR (Partial Response) and 1 patient had CR (Complete Response), and the total of 5 patients had clinical benefits (PR+SD≥24weeks) from the combination therapy.

The rGBM trial showed that 4 patients (44%) had SD (Stable Disease), including 1 patient staying on SD over 12 cycles. The median OS (Overall Survival) was 7.2 months vs 4 months, the average life span of rGBM patients.

"The interim results provide a strong rationale to proceed the mTNBC combination trial to Phase II," said Dr. Jin-San Yoo, CEO of PharmAbcine. "Despite the encouraging data from the rGBM study, we plan to pursue Phase II with mTNBC only for more efficient use of our resources. We just added three molecules with first-in-class potential in our pipeline and we need to be more careful with our resource utilization."

On September 14, 2020 Société des Produits Nestlé S.A. ("Nestlé") reported that its wholly-owned subsidiary, SPN Merger Sub, Inc. ("Purchaser"), is commencing today a cash tender offer to purchase all of the outstanding shares of common stock of Aimmune Therapeutics, Inc. (Nasdaq: AIMT) ("Aimmune") today for a price of USD 34.50 per share, net to the seller in cash, without interest and subject to any withholding taxes (the "Offer") (Press release, Nestlé, SEP 14, 2020, View Source [SID1234565131]). The Offer is being made upon the terms and subject to the conditions set forth in the Offer to Purchase (the "Offer to Purchase"), and related Letter of Transmittal and other related materials that will be filed by Nestlé and Purchaser with the United States Securities and Exchange Commission (the "SEC") on September 14, 2020 (collectively, the "Offering Materials") and pursuant to the terms of the previously announced Agreement and Plan of Merger, dated as of August 29, 2020 (the "Merger Agreement"), by and among Nestlé, Purchaser and Aimmune. In addition, Aimmune will file today a Solicitation/Recommendation Statement on Schedule 14D-9 and a Schedule 13E-3 transaction statement relating to the Offer with the SEC.

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The independent members of the board of directors of Aimmune have declared the Offer to be fair to and in the best interests of Aimmune and Aimmune’s stockholders (other than Nestlé and its affiliates) and recommend that such stockholders accept the Offer and tender their shares of Aimmune common stock pursuant to the Offer.

The Offer will expire at 12:00 midnight, Eastern time, on October 9, 2020, unless extended or earlier terminated (the time and date at which the Offer will expire, the "Expiration Date"). Any extension of the Offer will be announced in a press release or other public announcement before 9:00 a.m., Eastern time, on the first business day after the Expiration Date.

Copies of the Offering Materials are available free of charge by contacting MacKenzie Partners, the information agent for the Offer, toll-free at (800) 322-2885 or by email at [email protected] and, when filed, on the SEC’s website at www.sec.gov. Equiniti Trust Company is acting as the depositary for the Offer.

On September 14, 2020 OBI Pharma, Inc. (TPEx: 4174), a leader in Glycosphingolipid Immuno-Oncology therapeutics targeting the Globo Series antigens (Globo H and SSEA-4) and chemotherapeutics targeting AKR1C3, reported a scientific presentation will be held for OBI-999 (anti-Globo H targeted ADC) at the World ADC Digital Scientific meeting on Sept 16, 2020 (Press release, OBI Pharma, SEP 14, 2020, View Source [SID1234565130]).

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The scientific presentation titled, "A Novel Globo H-targeting Antibody-drug Conjugate: OBI 999" with a follow-up live discussion and question session will be led by Ming-Tain Lai, PhD. Chief Scientific Officer at OBI Pharma. The presentation will highlight the results from pre-clinical studies of OBI Pharma’s first-in-class anti-Globo H antibody drug conjugate (OBI-999), including animal efficacy and safety data, supporting the ongoing Phase 1/2 human study ongoing at the MD Anderson Cancer Center in Houston, TX (USA).

"OBI Pharma is proud to present at the prestigious 2020 World ADC Digital conference for OBI-999, our novel anti-Globo H first-in-class ADC cancer therapeutic. We look forward to providing future updates of our ongoing clinical studies, which could provide an important cancer ADC therapeutic option to patients suffering from cancer worldwide," stated Ming-Tain Lai, PhD.

Title: A Novel Globo H-targeting Antibody-drug Conjugate: OBI-999
Presenter: Ming-Tain Lai, PhD. Chief Scientific Officer at OBI Pharma, Inc. Taipei, Taiwan.
Presentation Date and Time: Wednesday, Sept. 16, 2020. 11:30 a.m. – 11:50 a.m. Eastern Time
Live Discussion & Question Session: Wednesday, Sept. 16, 2020. 12:30 p.m. Eastern Time

On September 14, 2020 Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high quality medicines for treatment of oncology, metabolic, autoimmune and other major diseases, and Eli Lilly and Company ("Lilly",NYSE: LLY) jointly reported that results of six clinical studies of TYVYT (sintilimab injection) will be presented during the upcoming European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) ("ESMO") Virtual Congress 2020 from September 19th to 21st (Press release, Innovent Biologics, SEP 14, 2020, View Source [SID1234565129]). The annual ESMO (Free ESMO Whitepaper) conference is among the most prestigious and influential global oncology conferences, during which oncologists around the world will share the latest research progress in cancer treatments.

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The six sintilimab studies to be presented at ESMO (Free ESMO Whitepaper) Virtual Congress include two LBAs (late-breaking abstracts, mini oral) and four e-posters (including two ongoing Phase 3 studies). The studies cover indications including lung cancer, gynecological cancer, hepatocellular carcinoma, gastric cancer, and other solid tumors. A brief summary of the studies is as follows:

Cancer Type: Lung Cancer

Presentation type: LBA (mini oral)

Biomarker Results from the ORIENT-11 Study (NCT 03607539): Finding biomarkers to accurately predict the efficacy of Immuno-combination therapy is still a hotspot and difficult issue in the study of PD-1 inhibitors. In the ORIENT-11 study, sequencing was conducted on baseline tumor biopsies to explore the association between immune related genes and clinical efficacy. The results could improve our understanding of the mechanism of action of immunotherapy-chemotherapy combination and provide a scientific rationale for future selection of suitable patients.

Researcher: Professor Yunpeng Yang, Sun Yat sen University cancer center

Results of the ORIENT-12 Study (NCT03629925): sintilimab plus gemcitabine and platinum chemotherapy as first-line treatment for locally advanced or metastatic squamous non-small-cell lung cancer (sqNSCLC). Clinical benefit from platinum-based chemotherapy for patients with advanced sqNSCLC is limited. Previous studies have shown the clinical benefits of the combination therapy of PD-1 inhibitor with paclitaxel/platinum chemotherapy as first-line treatment for sqNSCLC. In a Phase 1b cohort study, sintilimab in combination with gemcitabine/platinum chemotherapy has shown good efficacy and acceptable safety as first-line treatment for sqNSCLC. ORIENT-12 is a randomized, double-blind, Phase 3 study evaluating sintilimab or placebo in combination with gemcitabine and platinum chemotherapy as first-line treatment for locally advanced or metastatic sqNSCLC. ORIENT-12 has demonstrated for the first time survival benefit by treatment with PD-1 inhibitor in combination with gemcitabine and platinum chemotherapy in first-line sqNSCLC.

Researcher: Professor Caicun Zhou, Shanghai Pulmonary Hospital, Tongji University

Cancer Type: Hepatocellular carcinoma (HCC)

Presentation Type: e-poster

Sintilimab plus IBI305 (bevacizumab) as the first-line treatment for advanced HCC (NCT03794440). So far the treatment of first-line advanced HCC is limited with feasible choices such as sorafenib or lenvatinib. Immuno-oncology inhibitors have shown therapeutic value in HCC, with PD-L1 inhibitor (atezolizumab) in combination with a VEGF inhibitor reporting clinical benefits in unresectable or metastatic HCC patients before systemic treatment. This study will announce the safety and preliminary efficacy of combining PD-1 inhibitor and VEGF inhibitor in the first line treatment for patients with advanced unresectable or metastatic HCC. Currently sintilimab is undergoing Phase 2/3 study in combination with Byvasda (bevacizumab injection) in comparison with sorafenib in the first-line treatment of advanced HCC.

Researcher: Academician Jia Fan, Zhongshan Hospital, Fudan University

Cancer type: Gastric Cancer

Report type: e-poster

ORIENT-106 Study: To date, systemic chemotherapy remains the main choice for unresectable locally advanced or metastatic gastric cancer / gastroesophageal junction adenocarcinoma (G/GEJ). The prognosis of these patients is poor with the median overall survival (mOS) only about one year. Preclinical studies have shown that an anti-VEGF receptor 2 (VEGFR-2) antibody can restart the tumor microenvironment to avoid immunosuppression of tumor cells. In clinical studies, it was also observed that blocking PD-1 and VEGFR-2 at the same time could achieve synergistic anti-tumor effect. The ORIENT-106 study based on this theory is a multicenter, randomized, open label Phase 3 clinical trial to verify the efficacy and safety of sintilimab (IgG4 PD-1 inhibitor) and ramucirumab (IgG1 VEGFR-2 antagonist) as the first-line treatment for locally advanced or metastatic G/GEJ.

Researcher: President Ruihua Xu, Sun Yat sen University Cancer Center

Cancer type: Gynecological Tumor

Report type: e-poster

There are limited effective treatment for advanced cervical cancer patients who have previously received platinum-based chemotherapy. PD-1 inhibitor monotherapy has shown promising efficacy in patients with cervical cancer with positive PD-L1 expression. The combination of PD-1/PD-L1 inhibitors plus anti-angiogenesis drugs has shown significant anti-tumor activity in certain cancers. Professor Qin Xu from Fujian Cancer Hospital conducted a phase II study of sintilimab plus anlotinib for the treatment of advanced cervical cancer with positive PD-L1 expression. The study may potentially further improve the clinical outcomes of patients with advanced cervical cancer who have previously received platinum-based chemotherapy.

Researcher: Professor Qin Xu, Fujian Cancer Hospital

Cancer type: Solid Tumors

Report type: e-poster

The antitumor effect of chemotherapy combined with either PARP inhibitors or PD-1 inhibitors have been demonstrated in several studies, and previous researches have shown a synergetic effect of PARP inhibitors combining with PD-1 inhibitors. However, little was known regarding the combination of the three regimens. This is a phase 1b clinical study initiated by Professor Hu Yi of the Chinese PLA General Hospital, exploring the combination of sintilimab, platinum and niraparib (a PARP1/2 inhibitor) in the treatment of previously treated advanced solid tumors. The novel triple combination could potentially overcome resistance and further improve clinical outcomes of patients with advanced solid tumors who failed standard therapy.

Researcher: Professor Yi Hu, Chinese people’s Liberation Army General Hospital

On September 14, 2020 Ascentage Pharma (6855.HK), a globally focused, clinical-stage biotechnology company engaged in developing novel therapies for cancers, chronic hepatitis B (CHB), and age-related diseases, reported that the US Food and Drug Administration (FDA) has granted APG-115, a novel MDM2-p53 inhibitor being developed by the company, an Orphan Drug Designation (ODD) for the treatment of gastric cancer (GC) (Press release, Ascentage Pharma, SEP 14, 2020, View Source [SID1234565128]). This is the first ODD granted for APG-115.

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The term "orphan drugs" refers to pharmaceutical products developed for the prevention, diagnosis, and treatment of rare diseases or conditions. In the United States, an orphan disease is defined as a disease or condition with a prevalence of less than 200,000 patients in the country. Since the Orphan Drug Act was passed in 1983, the US government has provided incentives and policy support to encourage development of orphan drugs. This ODD from the FDA qualifies APG-115 for various development incentives, including a tax credit on expenditures incurred in clinical studies, a waiver of the New Drug Application (NDA) fee, research grant awarded by the FDA, and most importantly, 7 years of US market exclusivity upon approval for the treatment of GC.

The global incidence of GC is significantly different between eastern and western countries. According to the National Cancer Institute’s Surveillance, Epidemiology, and End Results Program, in 2017, there were an estimated 116,525 people living with GC in the US1. GC is currently considered as a rare disease in US. Asian countries such as China and Japan have a much higher incidence. GC is the third leading cause of cancer deaths worldwide, followed only by lung and colorectal cancer in overall mortality. About 1 in 12 of all oncological deaths are attributable to GC2.

The National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology for GC recommends a multidisciplinary approach for treatment of unresectable, advanced, metastatic GC patients. For patients with disease progression receiving second-line therapy, there are not many treatment options and the prognosis remains poor. Thus, effective treatment options are urgently needed3 to improve the disease outcome and reduce the mortality.

APG-115 is an orally administered, selective, small-molecule inhibitor of the MDM2-p53 protein-protein interaction (PPI). APG-115 has strong binding affinity to MDM2 and is designed to activate tumor suppression activity of p53 by blocking the MDM2-p53 PPI. APG-115 is the first MDM2-p53 inhibitor entering clinical development in China, with multiple ongoing clinical studies in solid tumors and hematologic malignancies in China and the US. APG-115 has shown promising results in preclinical studies for the treatment of GC.

"At present, the treatment of GC represents an urgent unmet clinical need globally. This ODD by the US FDA for the treatment of GC marks an important milestone in the global development and commercialization of APG-115," said Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma. "All the policy support and incentives as a result of this ODD will help us accelerate the global clinical development of APG-115, which we hope will soon transform to benefit more patients."

References:

1. 2020 Cancer Incidence Data, Surveillance, Epidemiology, and End Results Program, National Cancer Institute

2. Rawla, P., & Barsouk, A. (2019). Epidemiology of gastric cancer: global trends, risk factors and prevention.

3. Gastric Cancer, NCCN Clinical Practice Guidelines in Oncology, National Comprehensive Cancer Nerwork 2020.

About APG-115

APG-115 is an orally administered, selective, small-molecule inhibitor of the MDM2-p53 PPI. APG-115 has strong binding affinity to MDM2 and is designed to activate p53 tumor suppression activity by blocking the MDM2-p53 PPI. Ascentage Pharma has previously commenced three clinical trials of APG-115 in the US, including a Phase I study as single agent, a Phase Ib/II study in combination with pembrolizumab for treatment of metastatic melanoma and other advanced solid tumors, and a Phase I/II study as a single agent or in combination with chemotherapy for treatment of salivary gland cancer. APG-115 is the first MDM2-p53 inhibitor to enter clinical studies in China. A Phase I study as a single agent, and a Phase Ib study as a single agent or in combination with chemotherapy for treatment of AML (acute myeloid leukemia) or MDS (myelodysplastic syndrome) are ongoing in China.