On June 23, 2021 Certara, a global leader in biosimulation, reported that the Japanese Pharmaceuticals and Medical Devices Agency (PMDA) has renewed its licenses of Certara’s Simcyp and Phoenix biosimulation software (Press release, Certara, JUN 23, 2021, View Source [SID1234584301]). The PMDA has been using Certara’s biosimulation software since 2014.

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The Simcyp Physiologically-Based Pharmacokinetic (PBPK) Simulator is used in drug development to determine first-in-human dose, design more efficient and effective clinical studies, and predict drug-drug interactions using virtual populations. The Phoenix Pharmacokinetic and Pharmacodynamic (PK/PD) Platform is used for pharmacokinetic, pharmacodynamic, and toxicokinetic modeling and simulation to help drug developers save time by streamlining data management.

"The continued growth in modeling and simulation approaches for new drug applications in Japan is helping to support the development of medicines for difficult-to-treat diseases and for much needed areas, including pediatrics," said Certara’s CEO William Feehery, Ph.D. "Regulatory guidance and support are critical to expand new use cases for biosimulation to ultimately bring safe and efficacious therapies to patients."

Taking into account the increase in the use of exposure-response and PBPK analyses, two guidelines were issued by Japan’s Ministry of Health, Labour, and Welfare for the use of modeling and simulation in 2020: "Guideline for Drug Exposure‐Response Analysis" and "Guidelines for Analysis Reports Involving Physiologically based Pharmacokinetic Models."

According to a report presented in March 2021 at the PMDA Public Workshop of ‘Role of Model Informed Drug Development’, an increasing number of drug approval applications have used modeling and simulation to optimize dosing regimens and establish precautions in new drug application documents submitted to the PMDA. Certara works with more than 130 biopharmaceutical companies and research institutions in Japan, including all of the top 10 Japanese biopharmaceutical companies by R&D spend.

On June 22, 2021 Immutep Limited (ASX: IMM; NASDAQ: IMMP) (Immutep or Company), reported that it has received commitments for a A$60 million two-tranche private placement of new ordinary shares (New Shares) to professional, institutional and sophisticated investors (Placement) (Press release, Immutep, JUN 22, 2021, View Source [SID1234584214]).

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The first tranche of the Placement will be completed without shareholder approval. The second tranche of the Placement is subject to shareholders approval.

Use of Funds

The Company will use the proceeds received from the Placement to fund the expansion of its clinical programs and to commence the process characterisation and process validation for efti commercial manufacturing (2,000 litre scale). The proceeds received from the Placement will also be used for the offering costs and working capital purposes.

Placement

The Placement will involve the issue of New Shares at an issue price of A$0.52 per New Share (representing a 12.9% discount to the volume weighted average price (VWAP) of the Company’s ordinary shares as traded on ASX over the 30 days up to and including June 16, 2021). The New Shares issued under the Placement will rank equally with existing Immutep ordinary shares on issue with effect from their date of issue.

Settlement of the first tranche of the Placement is expected to occur on June 25, 2021, with the issuance of New Shares expected to occur on June 28, 2021.

Assuming Shareholder Approval is obtained for the completion of the second tranche of the Placement, settlement is expected to occur on July 29, 2021, with the issuance of New Shares expected to occur on July 30, 2021.

Share Purchase Plan

Following completion of the issue of the first tranche of the Placement, Immutep will conduct an offer of New Shares under a non-underwritten share purchase plan (SPP) to existing shareholders in the Company with a registered address in Australia and New Zealand as at 7.00pm (Sydney, Australia time) on June 18, 2021.

The SPP will provide each Eligible Shareholder with the opportunity to apply for up to A$30,000 of New Shares at the price payable per New Share in the Placement. The SPP is targeting to raise approximately A$5 million. The SPP is expected to close at 5.00pm (Sydney, Australia time) on July 22, 2021.

On June 22, 2021 Phio Pharmaceuticals Corp. (Nasdaq: PHIO), a biotechnology company developing the next generation of immuno-oncology therapeutics based on its proprietary self-delivering RNAi (INTASYL) therapeutic platform, reported that it has rescheduled the Company’s fireside chat being hosted by H.C. Wainwright, which was previously scheduled for today, to July 12, 2021 at 11 a.m. Eastern Time (Press release, Phio Pharmaceuticals, JUN 22, 2021, View Source [SID1234584230]). Details regarding the rescheduled fireside chat will be forthcoming.

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On June 22, 2021 Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high quality medicines for the treatment of oncology, metabolic, autoimmune and other major diseases, reported that the Phase 3 ORIENT-15 study met the predefined overall survival primary endpoint. ORIENT-15 is a global randomized, double-blind, multi-center clinical study evaluating sintilimab in combination with chemotherapy (cisplatin plus paclitaxel or cisplatin plus 5-fluorouracil [5-FU]) for the first-line treatment of patients with unresectable, locally advanced recurrent or metastatic esophageal squamous cell carcinoma (ESCC) (Press release, Innovent Biologics, JUN 22, 2021, View Source [SID1234584250]).

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Based on an interim analysis conducted by the Independent Data Monitoring Committee (IDMC), sintilimab in combination with chemotherapy demonstrated a statistically significant and clinically meaningful improvement in the primary endpoint of overall survival (OS) compared to placebo in combination with chemotherapy regardless of PD-L1 expression status. The safety profile of sintilimab in this study was consistent with that observed in previously reported studies of sintilimab, and no additional safety signals were identified. These results will be presented at an upcoming medical meeting.

The principal investigator of the ORIENT-15 study, Prof. Shen Lin from Peking University Cancer Hospital and Institute stated, "More than half of new and fatal cases of esophageal cancer in the world occur in China every year. In China, esophageal cancer is the fifth most commonly diagnosed cancer and the fourth leading cause of death from cancer, and squamous cell carcinoma (ESCC) is the predominant histologic type. Treatment options for people with ESCC are limited. Chemotherapy is currently the main treatment for ESCC and, in recent years, immunotherapy has brought new hope in the treatment of this type of cancer, with some PD-1 inhibitors receiving approval as a second-line treatment for patients with ESCC in China. We are encouraged by these interim results of the ORIENT-15 study which demonstrated that sintilimab in combination with chemotherapy prolonged overall survival in the first-line treatment of patients with ESCC, regardless of PD-L1 status."

Dr. Zhou Hui, Senior Vice President of Clinical Development of Innovent, stated: "The treatment options for locally advanced or metastatic ESCC are limited and represent a significant unmet clinical need. ORIENT-15 is the largest clinical study of sintilimab conducted by Innovent to date. Despite the COVID-19 pandemic, the joint effort of the study’s investigators and broader team have enabled us to reach this milestone. We would like to express our sincere gratitude to all the patients who participated in the ORIENT-15 study. We hope these results can help to provide a new treatment option for patients with ESCC."

About the ORIENT-15 Study

ORIENT-15 is a global randomized, double-blind, multi-center Phase 3 clinical study evaluating sintilimab in combination with chemotherapy (cisplatin plus paclitaxel or cisplatin plus 5-fluorouracil [5-FU]), compared to placebo in combination with chemotherapy, for the first-line treatment of unresectable, locally advanced recurrent or metastatic esophageal squamous cell carcinoma (ClinicalTrials.gov, NCT03748134). At the time of interim analysis, a total of 659 eligible patients were enrolled and randomly assigned into the experimental group or control group in a 1:1 ratio. Patients were enrolled regardless of PD-L1 status. The primary endpoints included overall survival in all randomized patients and overall survival in PD-L1 positive (defined as CPS ≥10) patients.

About Esophageal Squamous Cell Carcinoma (ESCC)

Esophageal cancer is one of the most common malignant tumors worldwide that begins in the inner layer (mucosa) of the esophagus, which connects the throat to the stomach. Based on GLOBOCAN 2020 estimates, approximately 600,000 new cases of esophageal cancer are diagnosed and approximately 540,000 deaths result from the disease globally. Esophageal cancer is the seventh most commonly diagnosed cancer and the sixth leading cause of death from cancer worldwide. More than half of new and fatal cases of esophageal cancer in the world occur in China. In China, it is estimated there were approximately 320,000 new cases of esophageal cancer diagnosed and approximately 300,000 deaths resulting from the disease in 2020. Esophageal cancer is the fifth most commonly diagnosed cancer and the fourth leading cause of death from cancer in China, which has a five-year survival rate of only 30 percent.

The two main types of esophageal cancer are squamous cell carcinoma (SCC) and adenocarcinoma. In China, SCC is the predominant histologic type – accounting for more than 90 percent of all esophageal cancer. Currently, first-line standard systemic therapy in China is chemotherapy based on platinum drugs for unresectable, locally advanced recurrent or metastatic ESCC. There have been a few PD-1 inhibitors recently approved for the second-line treatment of patients with ESCC.

About Sintilimab

Sintilimab, marketed as TYVYT (sintilimab injection) in China, is an innovative PD-1 inhibitor with global quality standards jointly developed by Innovent and Eli Lilly and Company. Sintilimab is an immunoglobulin G4 monoclonal antibody, which binds to PD-1 molecules on the surface of T-cells, blocks the PD-1 / PD-Ligand 1 (PD-L1) pathway, and reactivates T-cells to kill cancer cells. Innovent is currently conducting more than 20 clinical studies of sintilimab to evaluate its safety and efficacy in a wide variety of cancer indications, including more than 10 registrational or pivotal clinical trials.

In China, sintilimab has been approved for three indications, including:

The treatment of relapsed or refractory classic Hodgkin’s lymphoma after two lines or later of systemic chemotherapy
In combination with pemetrexed and platinum chemotherapy, for the first-line treatment of nonsquamous non-small cell lung cancer
In combination with gemcitabine and platinum chemotherapy, for the first-line treatment of squamous non-small cell lung cancer
Additionally, Innovent currently has regulatory submissions under review in China for sintilimab:

In combination with BYVASDA (bevacizumab injection) for the first-line treatment of hepatocellular carcinoma
The second-line treatment of squamous non-small cell lung cancer
Innovent also has two clinical studies that have met primary endpoint for sintilimab:

in combination with cisplatin plus paclitaxel or cisplatin plus 5-fluorouracil for the first-line treatment of esophageal squamous cell carcinoma
The second-line treatment for esophageal squamous cell carcinoma
In May 2021, the U.S. FDA accepted for review the Biologics License Application (BLA) for sintilimab in combination with pemetrexed and platinum chemotherapy for the first-line treatment of nonsquamous non-small cell lung cancer.

Sintilimab was included in China’s National Reimbursement Drug List (NRDL) in 2019 as the first PD-1 inhibitor and the only PD-1 included in the list in that year.

On June 22, 2021 Innate Pharma SA (Euronext Paris: IPH – ISIN: FR0010331421; Nasdaq: IPHA) ("Innate" or the "Company") reported preliminary data from the mycosis fungoides (MF) cohort of the Phase 2 TELLOMAK clinical trial, evaluating lacutamab, an anti-KIR3DL2 cytotoxicity-inducing antibody, in an oral presentation at the 16th International Conference on Malignant Lymphoma (16-ICML) (Press release, Innate Pharma, JUN 22, 2021, View Source [SID1234584215]).

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Lacutamab demonstrated clinical responses in patients with MF that express KIR3DL2 (cohort 2), reaching the pre-determined threshold to advance to stage 2.1

As of the May 10, 2021 data cutoff, in the KIR3DL2-expressing cohort (n=17), complete (n=1), partial (n=3) and unconfirmed partial (n=2) global responses were observed. Following the data cutoff, the two unconfirmed partial responses have been confirmed.

When evaluating responses in the skin, one patient had a complete response, eight patients had a partial response and two patients had an unconfirmed partial response. Out of seven patients with blood involvement, four had a complete response in the blood, and out of eight patients with lymph node involvement, one had a partial response. Following the data cutoff, the two unconfirmed partial responses in the skin have been confirmed.

All patients (n=19) in the KIR3DL2-non-expressing cohort (Cohort 3) have been recruited. The threshold of responses needed to advance to stage 2 has not been reached, and follow up is ongoing.

"We are pleased by the response demonstrated to date in patients with mycosis fungoides that express KIR3DL2, which has enabled us to advance this cohort earlier than expected," said Joyson Karakunnel, M.D., MSc, FACP, Chief Medical Officer of Innate Pharma. "These data confirm our initial hypothesis that lacutamab may benefit patients with KIR3DL2-expressing T-cell lymphomas, and support our data-driven approach in pursuit of a new standard of care in this population. Looking ahead, we continue to enroll patients in both the mycosis fungoides and Sézary syndrome cohorts of our TELLOMAK study. In addition, we plan to initiate our peripheral T-cell lymphoma program for lacutamab, with our Phase 1b monotherapy study expected to start mid-year and an investigator-sponsored combination study expected in the second half of this year."

In line with previous observations, lacutamab demonstrated a favorable safety profile in MF. Grades 1-2 treatment-related adverse events (AE) were observed, with one patient (out of 36) experiencing a grade 3 AE. No relevant skin toxicities were observed.

"Mycosis fungoides, and cutaneous T-cell lymphomas more broadly, are associated with poor clinical outcomes, particularly at advanced stages," said Pr. Martine Bagot, Head of the Dermatology Department, Saint Louis Hospital, Paris, and a study investigator. "The clinical responses and favorable safety profile observed in the TELLOMAK study are quite encouraging so far. I am particularly pleased by the preliminary skin responses, as relapsed/refractory patients are in need of new treatment options that can improve their quality of life, and slow disease progression. I look forward to seeing more data from lacutamab as this trial progresses with the enrollment of additional patients in this cohort."

Innate will provide additional information on these results tomorrow, June 23, 2021, in an investor event scheduled for 2:00 p.m. CEST / 8:00 a.m. EDT. Details to access the live event are available in the investors section of Innate’s website, where a replay of the webcast will also be archived for 90 days following the event.

About Lacutamab:

Lacutamab (IPH4102) is a first-in-class anti-KIR3DL2 humanized cytotoxicity-inducing antibody that is currently in clinical trials for treatment of cutaneous T-cell lymphoma (CTCL), an orphan disease. This group of rare cutaneous lymphomas of T lymphocytes has a poor prognosis with few efficacious and safe therapeutic options at advanced stages.

KIR3DL2 is an inhibitory receptor of the KIR family, expressed by approximately 65% of patients across all CTCL subtypes and expressed by up 90% of patients with certain aggressive CTCL subtypes, in particular, Sézary syndrome. It is expressed by up to 50% of patients with mycosis fungoides and peripheral T-cell lymphoma (PTCL). It has a restricted expression on normal tissues.

About TELLOMAK:

TELLOMAK is a global, open-label, multi-cohort Phase 2 clinical trial recruiting patients with Sézary syndrome and mycosis fungoides (MF) in the United States and Europe. Specifically:

Cohort 1: lacutamab being evaluated as a single agent in approximately 60 patients with Sézary syndrome who have received at least two prior systemic therapies, including mogamulizumab.
Cohort 2: lacutamab being evaluated as a single agent in up to approximately 50 patients with MF that express KIR3DL2, as determined at baseline.
Cohort 3: lacutamab being evaluated as a single agent in up to approximately 38 patients with MF that do not express KIR3DL2, as determined at baseline.
The MF cohorts follow a Simon 2-stage design that will terminate early if treatment is considered futile. The Sézary syndrome cohort of the study could enable the registration of lacutamab in this indication.

The primary endpoint of the trial is objective global response rate. Key secondary endpoints are progression-free survival, duration of response, quality of life and adverse events.

Global response in cutaneous lymphoma is measured by the guidelines published by Olsen et. al in the Journal of Clinical Oncology in 2011.2