On August 18, 2020 Immutep Limited (ASX: IMM; NASDAQ: IMMP) ("Immutep" or "the Company"), a biotechnology company developing novel immunotherapy treatments for cancer and autoimmune diseases, reported it has enrolled and safely dosed the last patient for stage 1 of Part B of its TACTI-002 Phase II study, completing recruitment of stage 1 of Part B (Press release, Immutep, AUG 18, 2020, View Source [SID1234563756]).

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Based on the study’s Simon’s two-stage clinical trial design, safety and efficacy data will be provided to the Data Monitoring Committee (DMC) for its review and recommendation regarding opening recruitment into stage 2 of Part B once all patients have undergone at least one tumour imaging after treatment.

TACTI-002 is being conducted in collaboration with Merck & Co., Inc., Kenilworth, NJ, USA (known as "MSD" outside the United States and Canada) and is evaluating the combination of Immutep’s lead product candidate, eftilagimod alpha ("efti" or "IMP321") with MSD’s KEYTRUDA (pembrolizumab) in up to 109 patients with second line Head and Neck Squamous Cell Carcinoma (HNSCC) or NSCLC in first and second line.

TACTI-002 Recruitment

Recruitment details for each Part of TACTI-002 are below. At present, recruitment is ongoing for Stage 2 of Part C. Pending the DMC’s recommendation, Immutep will consider opening stage 2 of Part B for recruitment.

Stage 1 (N)
Actual/target Stage 2 (N)
Actual /target Recruitment
status
Part A (1st line NSCLC)

17/17 19/19 COMPLETE
Part B (2nd line NSCLC)

23/23 -/13 TBA
Part C (2nd line HNSCC)

18/18 10/19 ONGOING
About the TACT-002 Trial

TACTI-002 (Two ACTive Immunotherapies) is being conducted in collaboration with Merck & Co., Inc., Kenilworth, NJ, USA (known as "MSD" outside the United States and Canada). The study is evaluating the combination of efti with MSD’s KEYTRUDA (pembrolizumab) in up to 109 patients with second line head and neck squamous cell carcinoma or non-small cell lung cancer in first and second line.

The trial is a Phase II, Simon’s two-stage, non-comparative, open-label, single-arm, multicentre clinical study that is taking place in up to 12 study centres across the U.S., Europe and Australia.

Immutep Limited, Level 12, 95 Pitt Street, Sydney NSW 2000

ABN: 90 009 237 889

TACTI-002 is an all comer study in terms of PD-L1 status, a well-known predictive marker for response to pembrolizumab monotherapy especially in NSCLC. PD-L1 expression is typically reported in three groups for NSCLC: < 1%, 1-49% and ³50% (Tumour Proportion Score or TPS). Patients with a high PD-L1 status are typically more responsive to anti-PD-1 monotherapy such as pembrolizumab, whereas those with low PD-L1 status are overall significantly less responsive. Pembrolizumab monotherapy is registered in the US and the EU for first-line NSCLC patients with a TPS score ³1% (US) and ³50% (EU), reflecting 65% and 30% of all first line NSCLC patients, respectively.

On August 18, 2020 Eli Lilly and Company (NYSE: LLY) and Innovent Biologics, Inc. (HKEX: 01801) reported a global expansion of their strategic alliance for TYVYT (sintilimab injection), an anti-PD-1 monoclonal antibody immuno-oncology medicine that was co-developed by Innovent and Lilly in China (Press release, Eli Lilly, AUG 18, 2020, View Source [SID1234563755]).

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In 2019, Lilly and Innovent began commercializing TYVYT in China after being granted marketing approval for relapsed or refractory classic Hodgkin’s lymphoma after at least two lines of systemic chemotherapy. TYVYT is the only PD-1 inhibitor to be included in China’s National Reimbursement Drug List (NRDL) and is included in the 2019 Guidelines of Chinese Society of Clinical Oncology for Lymphoid Malignancies.

Lilly and Innovent currently co-commercialize TYVYT in China. Under the terms of the expanded license agreement, Lilly will obtain an exclusive license for TYVYT for geographies outside of China and plans to pursue registration of TYVYT in the U.S. and other markets. In return, Innovent will receive an upfront payment of $200 million and will be eligible for up to $825 million in potential development and commercial milestones, as well as tiered double-digit royalties on net sales. Both companies will also retain the right to study TYVYT in combination with other medicines as part of their own clinical programs.

The two companies are also studying TYVYT as a potential therapy in non-squamous non-small cell lung cancer (NSCLC) and several other types of cancer. Earlier this month, the two companies released encouraging interim analysis data from ORIENT-11 at the IASLC World Conference on Lung Cancer 2020 Virtual Presidential Symposium. ORIENT-11 is a randomized, double-blind, Phase 3 clinical trial evaluating TYVYT or placebo in combination with Alimta (pemetrexed for injection) and platinum chemotherapy as a first-line treatment for advanced or recurrent non-squamous NSCLC without sensitizing EGFR mutations or ALK rearrangements. Based on the interim analysis conducted by the Independent Data Monitoring Committee, TYVYT in combination with Alimta and platinum chemotherapy demonstrated a statistically significant improvement in progression-free survival compared with placebo in combination with Alimta and platinum chemotherapy, which met the pre-defined efficacy criteria. A supplemental New Drug Application (sNDA) for this indication is under regulatory review in China. The companies look forward to future submissions with the U.S. Food and Drug Administration and other regulatory agencies for this and other indications.

"We are thrilled to expand on our successful China TYVYT collaboration with Lilly to now include markets outside of China. This agreement also marks the first solid step in getting Innovent’s innovative portfolio into the global market," said Michael Yu, Ph.D., Founder, Chairman and CEO of Innovent. "We are confident that pairing Lilly’s global commercial expertise with TYVYT’s clinical profile will further accelerate our mission, benefitting patients globally."

"Lilly Oncology is dedicated to delivering life-changing medicines and support to people living with cancer and those who care for them," said Anne White, president of Lilly Oncology. "Our alliance with Innovent successfully brought TYVYT to market in China. Through this expansion of our collaboration, we hope to make TYVYT accessible to patients globally. We believe TYVYT could deliver significant value to people living with cancer around the world and we intend to continue to study its potential across tumor types."

This transaction is subject to customary closing conditions, including clearance under the Hart-Scott-Rodino Antitrust Improvements Act. The transaction will be reflected in Lilly’s reported results and financial guidance according to Generally Accepted Accounting Principles (GAAP). There will be no change to Lilly’s 2020 non-GAAP earnings per share guidance as a result of this transaction.

About TYVYT (Sintilimab Injection)
TYVYT (sintilimab injection) is an innovative drug with global quality standards jointly developed by Innovent and Lilly in China. TYVYT has been granted marketing approval by the NMPA for the treatment of relapsed or refractory classic Hodgkin’s lymphoma after at least two lines of systemic chemotherapy and was included in the 2019 Guidelines of Chinese Society of Clinical Oncology for Lymphoid Malignancies.

In April 2020, the NMPA accepted the supplemental new drug application for TYVYT in combination with ALIMTA (pemetrexed for injection) and platinum as first-line therapy in advanced or recurrent non-squamous non-small cell lung cancer (NSCLC). In May 2020, TYVYT combined with gemcitabine and platinum chemotherapy met the predefined primary endpoint in the Phase 3 ORIENT-12 study as first-line therapy in patients with locally advanced or metastatic squamous NSCLC. TYVYT monotherapy met the primary endpoint in the ORIENT-2 study as second-line therapy in patients with advanced or metastatic esophageal squamous cell carcinoma as well. In August 2020, the NMPA accepted the sNDA for TYVYT in combination with gemcitabine and platinum chemotherapy as first-line therapy in patients with locally advanced or metastatic squamous NSCLC.

TYVYT is a type of 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 with TYVYT to evaluate its safety and efficacy in a wide variety of cancer indications, including more than 10 registrational or pivotal clinical trials.

TYVYT (sintilimab injection) is not an approved product in the United States. ALIMTA(pemetrexed for injection) is not approved for use in combination with TYVYT in the United States.

U.S. INDICATIONS FOR ALIMTA (pemetrexed for injection)
ALIMTA is indicated:

in combination with pembrolizumab and platinum chemotherapy for the initial treatment of patients with nonsquamous metastatic non-small cell lung cancer (mNSCLC) with no EGFR or ALK genomic tumor aberrations.
in combination with cisplatin for the initial treatment of patients with locally advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC).
as a single agent for the maintenance treatment of patients with locally advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC) whose disease has not progressed after four cycles of platinum-based first-line chemotherapy.
as a single agent for the treatment of patients with recurrent metastatic nonsquamous non-small cell lung cancer (NSCLC) after prior chemotherapy. Limitation of Use: ALIMTA is not indicated for the treatment of patients with squamous cell non-small cell lung cancer.
in combination with cisplatin, for the initial treatment of patients with malignant pleural mesothelioma (MPM) whose disease is unresectable or who are otherwise not candidates for curative surgery.
U.S. IMPORTANT SAFETY INFORMATION FOR ALIMTA (pemetrexed for injection)
CONTRAINDICATION

ALIMTA is contraindicated in patients who have a history of severe hypersensitivity reaction to pemetrexed.
WARNINGS AND PRECAUTIONS
Myelosuppression and Increased Risk of Myelosuppression Without Vitamin Supplementation

ALIMTA can cause severe myelosuppression resulting in a requirement for transfusions and which may lead to neutropenic infection. The risk of myelosuppression is increased in patients who do not receive vitamin supplementation.
Prior to treatment with ALIMTA, patients must be instructed to initiate supplementation with oral folic acid. Intramuscular injections of vitamin B12 are also required prior to ALIMTA treatment. Folic acid and vitamin B12 supplementation should be continued during treatment and for 21 days after the last dose of ALIMTA as they may reduce the severity of treatment-related hematologic and gastrointestinal toxicities. Obtain a complete blood count at the beginning of each cycle. Do not administer ALIMTA until the ANC is at least 1500 cells/mm3 and platelet count is at least 100,000 cells/mm3. Permanently reduce ALIMTA in patients with an ANC of less than 500 cells/mm3 or platelet count of less than 50,000 cells/mm3 in previous cycles.
In Studies JMDB and JMCH, among patients who received vitamin supplementation, incidence of Grade 3-4 neutropenia was 15% and 23%, the incidence of Grade 3-4 anemia was 6% and 4%, and incidence of Grade 3-4 thrombocytopenia was 4% and 5%, respectively. In Study JMCH, 18% of patients in the ALIMTA arm required red blood cell transfusions compared to 7% of patients in the cisplatin arm. In Studies JMEN, PARAMOUNT, and JMEI, where all patients received vitamin supplementation, incidence of Grade 3-4 neutropenia ranged from 3% to 5%, and incidence of Grade 3-4 anemia ranged from 3% to 5%.
Renal Failure

ALIMTA can cause severe, and sometimes fatal, renal toxicity. Determine creatinine clearance before each dose and periodically monitor renal function during treatment with ALIMTA.
The incidences of renal failure in clinical studies in which patients received ALIMTA with cisplatin were 2.1% in Study JMDB and 2.2% in Study JMCH. The incidence of renal failure in clinical studies in which patients received ALIMTA as a single agent ranged from 0.4% to 0.6% (Studies JMEN, PARAMOUNT, and JMEI).
Withhold ALIMTA in patients with a creatinine clearance of less than 45 mL/min.
Bullous and Exfoliative Skin Toxicity

Serious and sometimes fatal, bullous, blistering, and exfoliative skin toxicity, including cases suggestive of Stevens-Johnson Syndrome/toxic epidermal necrolysis, can occur with ALIMTA. Permanently discontinue ALIMTA for severe and life-threatening bullous, blistering, or exfoliating skin toxicity.
Interstitial Pneumonitis

Serious interstitial pneumonitis, including fatal cases, can occur with ALIMTA treatment. Withhold ALIMTA for acute onset of new or progressive unexplained pulmonary symptoms such as dyspnea, cough, or fever pending diagnostic evaluation. If pneumonitis is confirmed, permanently discontinue ALIMTA.
Radiation Recall

Radiation recall can occur with ALIMTA in patients who have received radiation weeks to years previously. Monitor patients for inflammation or blistering in areas of previous radiation treatment. Permanently discontinue ALIMTA for signs of radiation recall.
Increased Risk of Toxicity With Ibuprofen in Patients With Renal Impairment

Exposure to ALIMTA is increased in patients with mild to moderate renal impairment who take concomitant ibuprofen, increasing the risks of adverse reactions of ALIMTA. In patients with creatinine clearances between 45 mL/min and 79 mL/min, avoid administration of ibuprofen for 2 days before, the day of, and 2 days following administration of ALIMTA. If concomitant ibuprofen use cannot be avoided, monitor patients more frequently for ALIMTA adverse reactions, including myelosuppression, renal, and gastrointestinal toxicity.
Embryo-Fetal Toxicity

Based on findings from animal studies and its mechanism of action, ALIMTA can cause fetal harm when administered to a pregnant woman. In animal reproduction studies, intravenous administration of pemetrexed to pregnant mice during the period of organogenesis was teratogenic, resulting in developmental delays and increased malformations at doses lower than the recommended human dose of 500 mg/m2. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with ALIMTA and for 6 months after the final dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with ALIMTA and for 3 months after the final dose.
DRUG INTERACTIONS

Ibuprofen increases exposure (AUC) of pemetrexed. In patients with creatinine clearance between 45 mL/min and 79 mL/min:
Avoid administration of ibuprofen for 2 days before, the day of, and 2 days following administration of ALIMTA.
Monitor patients more frequently for myelosuppression, renal, and gastrointestinal toxicity, if concomitant administration of ibuprofen cannot be avoided.
ADVERSE REACTIONS

Severe adverse reactions (Grade 3-4) occurring in ≥20% of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC) receiving ALIMTA in combination with pembrolizumab and platinum chemotherapy (carboplatin or cisplatin) versus ALIMTA with platinum chemotherapy + placebo for initial treatment (KEYNOTE-189), respectively, were fatigue (12% vs 6%); diarrhea (5% vs 3%); dyspnea (3.7% vs 5%); vomiting (3.7% vs 3%); nausea (3.5% vs 3.5%); rash (2% vs 2.5%); decreased appetite (1.5% vs 0.5%); constipation (1% vs 0.5%); and pyrexia (0.2% vs 0%).
Common adverse reactions (all grades) occurring in ≥20% of patients with metastatic nonsquamous non-small cell lung cancer (NSCLC) receiving ALIMTA in combination with pembrolizumab and platinum chemotherapy (carboplatin or cisplatin) versus ALIMTA with platinum chemotherapy + placebo for initial treatment (KEYNOTE-189), respectively, were nausea (56% vs 52%); fatigue (56% vs 58%); constipation (35% vs 32%); diarrhea (31% vs 21%); decreased appetite (28% vs 30%); rash (25% vs 17%); vomiting (24% vs 23%); cough (21% vs 28%); dyspnea (21% vs 26%); and pyrexia (20% vs 15%).
USE IN SPECIFIC PATIENT POPULATIONS

Lactation: There is no information regarding the presence of pemetrexed or its metabolites in human milk, the effects on the breastfed infant, or the effects on milk production. Because of the potential for serious adverse reactions in breastfed infants from ALIMTA, advise women not to breastfeed during treatment with ALIMTA and for one week after the last dose.
Males of Reproductive Potential: ALIMTA may impair fertility in males of reproductive potential. It is not known whether these effects on fertility are reversible.
Pediatric Use: The safety and effectiveness of ALIMTA in pediatric patients have not been established. Adverse reactions observed in pediatric patients studied were similar to those observed in adults.
Patients with Renal Impairment: ALIMTA is primarily excreted by the kidneys. Decreased renal function results in reduced clearance and greater exposure (AUC) to ALIMTA compared with patients with normal renal function. No dose is recommended for patients with creatinine clearance less than 45 mL/min.
Geriatric: The incidences of Grade 3-4 anemia, fatigue, thrombocytopenia, hypertension, and neutropenia were higher in patients 65 years of age and older as compared to younger patients: in at least one of five randomized clinical trials.
PM_HCP_ISI_NSCLC1L_Combo_30JAN2019

For U.S. safety and dosing guidelines for ALIMTA, see complete Warnings and Precautions, Adverse Reactions, and Dosage and Administration sections in the full U.S. Prescribing Information and Patient Prescribing Information.

ALIMTA is a registered trademark owned by or licensed to Eli Lilly and Company, its subsidiaries, or affiliates.

About Innovent Biologics’ strategic cooperation with Eli Lilly and Company
Innovent entered into a strategic collaboration with Lilly focusing on biological medicine in March 2015 – a groundbreaking partnership between a Chinese pharmaceutical company and a multinational pharmaceutical company. Under the agreement, Innovent and Lilly are co-developing and commercializing oncology medicines, including TYVYT (sintilimab injection) in China. In October 2015, the two companies announced the extension of their existing collaboration to include co-development of three additional antibodies targeting oncology indications. In August 2019, Innovent entered into an additional licensing agreement with Lilly to develop and commercialize a potentially global best-in-class diabetes medicine in China. In August 2020, Innovent and Lilly announced an expansion of their strategic alliance for TYVYT. Its collaboration with Lilly indicates that Innovent has established a comprehensive level of cooperation between China’s innovative pharmaceuticals sector and the international pharmaceuticals sector in areas such as R&D, CMC, clinical development and commercialization.

On August 18, 2020 AstraZeneca’s Imfinzi (durvalumab) reported that it has received acceptance for its supplemental Biologics License Application (sBLA) and has also been granted Priority Review in the US for a new four-week, fixed-dose regimen for treatment in the approved indications of non-small cell lung cancer (NSCLC) and bladder cancer (Press release, AstraZeneca, AUG 18, 2020, View Source [SID1234563745]).

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If approved, Imfinzi could be administered intravenously every four weeks at a fixed dose of 1500mg in unresectable Stage III NSCLC after chemoradiation therapy and previously treated advanced bladder cancer, consistent with the approved dosing in extensive-stage small cell lung cancer (ES-SCLC).

The Food and Drug Administration (FDA) grants Priority Review to applications for medicines that offer significant advances over available options by demonstrating safety or efficacy improvements, preventing serious conditions, or enhancing patient compliance. The Prescription Drug User Fee Act date, the FDA action date for their regulatory decision, is during the fourth quarter of 2020.

If approved, the new dosing will be available as an alternative to the approved weight-based dosing of 10mg/kg every two weeks. The sBLA was based on data from several Imfinzi clinical trials, including results from the Phase III CASPIAN trial in ES-SCLC which used the four-week, fixed-dose regimen during maintenance.

Dave Fredrickson, Executive Vice President, Oncology Business Unit, said: "The new less-frequent dosing option for non-small cell lung cancer and bladder cancer will simplify and improve treatment by enabling continuity of care while minimising the risk of exposure to infection in the healthcare setting. This takes on particular urgency during the current pandemic, as doctors care for patients at high risk of COVID-19 complications. We are working with health authorities in the US and other countries to bring the option of four-week, fixed dosing for Imfinzi to patients around the world as soon as we can."

Imfinzi is approved in the curative-intent setting of unresectable, Stage III NSCLC after chemoradiation therapy in the US, Japan, China, across the EU and in many other countries, based on the Phase III PACIFIC trial. Imfinzi is also approved for previously treated patients with advanced bladder cancer in the US and several other countries. Additionally, it is approved in the US and under review in Japan and other countries for ES-SCLC. Imfinzi was also recently recommended for marketing authorisation in the EU for this indication.

Stage III NSCLC

Stage III (locally-advanced) NSCLC is commonly divided into three sub-categories (IIIA, IIIB and IIIC), defined by how much the cancer has spread locally and the possibility of surgery.1 Stage III disease is different from Stage IV disease, when the cancer has spread (metastasised), as the majority of Stage III patients are currently treated with curative intent.1,2

Stage III NSCLC represents approximately one-third of NSCLC incidence and in 2015 was estimated to affect nearly 200,000 patients in the following eight key countries: China, France, Germany, Italy, Japan, Spain, UK, and the US, with approximately 43,000 cases in the US alone.3,4 The majority of Stage III NSCLC patients are diagnosed with unresectable tumours.5 Prior to approval of Imfinzi in this setting, no new treatments beyond chemoradiation therapy had been available to patients for decades.6-9

Bladder cancer

In 2018, approximately 550,000 people were diagnosed with bladder cancer around the world and 200,000 died from the disease.10 Locally advanced and metastatic bladder cancer remains an area of unmet medical need and typically only one in seven patients are alive five years after diagnosis.11 Urothelial cancer (UC) is the most common form of bladder cancer.12 UC is the 10th most common cancer worldwide and the 13th most common cause of cancer death.10,13 PD-L1 is widely expressed in tumour and immune cells in patients with bladder cancer and helps tumours evade detection from the immune system.14

Imfinzi

Imfinzi (durvalumab) is a human monoclonal antibody that binds to PD-L1 and blocks the interaction of PD-L1 with PD-1 and CD80, countering the tumour’s immune-evading tactics and releasing the inhibition of immune responses.

As part of a broad development programme, Imfinzi is also being tested as a monotherapy and in combination with tremelimumab, an anti-CTLA4 monoclonal antibody and potential new medicine, as a treatment for patients with NSCLC, SCLC, bladder cancer, head and neck cancer, liver cancer, biliary tract cancer, cervical cancer and other solid tumours.

AstraZeneca in lung cancer

AstraZeneca has a comprehensive portfolio of approved and potential new medicines in late-stage development for the treatment of different forms of lung cancer spanning different histologies, several stages of disease, lines of therapy and modes of action. AstraZeneca aims to address the unmet needs of patients with EGFR-mutated tumours as a genetic driver of disease, which occur in 10-15% of NSCLC patients in the US and EU and 30-40% of NSCLC patients in Asia, with the approved medicines Iressa (gefitinib) and Tagrisso (osimertinib) and its ongoing Phase III trials LAURA, NeoADAURA and FLAURA2.15-17

AstraZeneca is committed to addressing tumour mechanisms of resistance through the ongoing Phase II trials SAVANNAH and ORCHARD which test Tagrisso in combination with savolitinib, a selective inhibitor of c-MET receptor tyrosine kinase, along with other potential new medicines. Enhertu (trastuzumab deruxtecan), a HER2-directed antibody drug conjugate, is in development for metastatic non-squamous HER2-overexpressing or HER2-mutated NSCLC including trials in combination with other anticancer treatments. In addition, DS-1062, a trophoblast cell-surface antigen 2 (TROP2)-directed ADC, is in early development for advanced NSCLC where TROP2 is overexpressed in the majority of tumours.18

An extensive Immuno-Oncology development programme focuses on lung cancer patients without a targetable genetic mutation which represents up to three-quarters of all patients with lung cancer.19 Imfinzi, an anti-PDL1 antibody, is in development for patients with advanced disease (Phase III trials POSEIDON and PEARL) and for patients in earlier stages of disease including potentially-curative settings (Phase III trials MERMAID-1, AEGEAN, ADJUVANT BR.31, PACIFIC-2, PACIFIC-4, PACIFIC-5, and ADRIATIC) both as monotherapy and in combination with tremelimumab and/or chemotherapy. Imfinzi is also in development in the Phase II trials NeoCOAST, COAST and HUDSON in combination with potential new medicines from the early-stage pipeline including Enhertu.

AstraZeneca’s approach to Immuno-Oncology

Immuno-oncology (IO) is a therapeutic approach designed to stimulate the body’s immune system to attack tumours. The Company’s IO portfolio is anchored by immunotherapies that have been designed to overcome anti-tumour immune suppression. AstraZeneca is invested in using IO approaches that deliver long-term survival for new groups of patients across tumour types.

The Company is pursuing a comprehensive clinical-trial programme that includes Imfinzi as a monotherapy and in combination with tremelimumab in multiple tumour types, stages of disease, and lines of therapy, and where relevant using the PD-L1 biomarker as a decision-making tool to define the best potential treatment path for a patient. In addition, the ability to combine the IO portfolio with radiation, chemotherapy, small targeted molecules from across AstraZeneca’s Oncology pipeline, and from research partners, may provide new treatment options across a broad range of tumours.

AstraZeneca in oncology

AstraZeneca has a deep-rooted heritage in oncology and offers a quickly growing portfolio of new medicines that has the potential to transform patients’ lives and the Company’s future. With seven new medicines launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, the Company is committed to advance oncology as a key growth driver for AstraZeneca focused on lung, ovarian, breast and blood cancers.

By harnessing the power of four scientific platforms – Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response and Antibody Drug Conjugates – and by championing the development of personalised combinations, AstraZeneca has the vision to redefine cancer treatment and, one day, eliminate cancer as a cause of death.

On August 18, 2020 Photocure ASA (OSE:PHO) reported Hexvix/Cysview revenues of 53.5 million in the second quarter of 2020 (Q2 2019: NOK 52.1), corresponding to growth of three per cent, despite a significant Covid-19 impact in the beginning of the quarter in the U.S. market before a strong recovery towards the end of the period (Press release, PhotoCure, AUG 18, 2020, View Source [SID1234563726]). The company has entered into an agreement with Ipsen Pharma SAS (Ipsen) for the return of Hexvix sales, marketing and distribution rights from the fourth quarter of 2020 and sees significant growth opportunities in Europe. The agreement is expected to be EBITDA accretive from full-year 2021 and beyond.

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"Our second quarter results were negatively impacted by the Covid-19 pandemic with a significant decline in revenue at the beginning of the quarter but a strong recovery towards the end of the quarter. We are confident that we will return to strong growth rates with continued growth year over year once the Covid-19 epidemic subsides. We believe that BLC with Hexvix/Cysview can play an integral role in assuring that the first TURBT in a patient after postponement of procedures due to Covid-19 will be complete and thorough reducing the risks for repeat TURBT, reoccurrence and progression in that patient," says Daniel Schneider, President & Chief Executive Officer of Photocure.

Photocure reported total group revenues of NOK 53.7 million in the second quarter of 2020 (NOK 53.0 million), with an EBITDA before restructuring of NOK -8.9 million (NOK -2.6 million). The Hexvix/Cysview revenues ended at NOK 53.5 million (NOK 52.1 million). The demand in the U.S. market rebounded at the end of the quarter, with the in-market unit sales for June up 7 per cent compared to June last year.

The installed base of rigid cystoscopes in the U.S. was 246 at the end of the second quarter, an increase of 58 units or 31% since the same quarter last year. Blue Light Cystoscopy (BLCTM) in the surveillance setting is a key priority for Photocure in the U.S. market. By the end of the second quarter, 30 flexible cystoscopes for the surveillance cystoscopy setting have been installed.

Cash balance of NOK 500 million

Photocure had a net cash flow from operations of NOK 11.4 million in the second quarter of 2020 (NOK -4.0 million) and completed two private placements on 27 April and 24 June, raising a total gross of NOK 333 million. The private placements attracted very strong interest from existing shareholders, as well as from new high-quality institutional investors and were multiple times oversubscribed. At the end of the quarter, Photocure had a cash balance of NOK 499.4 million (86.7).

Regains worldwide rights of Hexvix

Photocure has entered into an agreement with Ipsen for the return of Hexvix sales, marketing and distribution rights in Europe and other markets currently controlled by Ipsen. With taking direct control over Photocure’s own Hexvix/Cysview product in key regions, the company supports the ambition of becoming a global leader in bladder cancer with a solid basis for expansion and further growth opportunities. Photocure will commence the Hexvix commercialization in Europe from the fourth quarter of 2020 and expects the Ipsen agreement to be EBITDA accretive from full-year 2021 and beyond.

"In June, we signed the final agreement with Ipsen for the return of the marketing and sales rights for Hexvix in various European countries. This transaction further supports our strategy of building a strong and profitable global business within bladder cancer. We plan to leverage the extensive experience we have built in the U.S. and the Nordics to the markets that were previously controlled by Ipsen. We believe there is tremendous growth and expansion opportunities in all markets previously controlled by Ipsen. In addition, there are many markets where Ipsen never commercialized our products and we plan to address many of these markets in the future. In the second quarter, we successfully raised the necessary capital to fund the required milestone payments, training of people and working capital to transition the European business from Ipsen to Photocure," says Schneider.

Group 2023 ambitions

Photocure delivers transformative solutions that improve the lives of bladder cancer patients. Based on experience and the performance of the breakthrough bladder cancer product Hexvix/Cysview, Photocure has embarked on a stepwise approach for continued growth. Photocure sees significant long-term potential in the global bladder cancer market and has a defined growth strategy:

Accelerating – Drive the breadth and depth of Hexvix/Cysview usage in key accounts
Expanding – Generate sales in new geographies and product enhancements
Acquiring – Products used in the management of bladder cancer patients
Transforming – Partner and in-license assets to strengthen the bladder cancer portfolio
"Based on the outlook and strategic opportunities, Photocure aims to maintain its group revenue ambitions for 2023 in the range of NOK 1 billion with EBITDA margins of approximately 40%, following the completion of the transaction with Ipsen," Schneider concludes.

Please find the full financial report and presentation enclosed.

EBITDA and other alternative performance measures (APMs) are defined and reconciled to the IFRS financial statements as a part of the APM section of the second quarter 2020 financial report on page 22-23.

Photocure will present its second quarter 2020 report on Tuesday 18 August 2020 at 14:00 CET. The investor presentation will be streamed live and be hosted by Daniel Schneider, CEO and Erik Dahl, CFO.

The presentation will be held in English and questions can be submitted throughout the event. The streaming event is available through https://channel.royalcast.com/webcast/hegnarmedia/20200818_11/ . The presentation is scheduled to conclude at 14:45 CET.

On August 18, 2020 BerGenBio ASA (OSE:BGBIO), a clinical-stage biopharmaceutical company developing novel, selective AXL kinase inhibitors for unmet medical need indications, reported its results for the second quarter and first half of 2020 (Press release, BerGenBio, AUG 18, 2020 View Source [SID1234563725]).

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A presentation and live webcast by BerGenBio’s senior management will take place at 10.00 am CET today, please see below for details.

Richard Godfrey, Chief Executive Officer of BerGenBio, commented: "Set against the unprecedented backdrop of a global pandemic, this has been an eventful period for BerGenBio. During this time we have continued our focus on progressing clinical trials of our lead candidate bemcentinib in non-small cell lung cancer (NSCLC) and Acute Myeloid Leukaemia (AML) and more recently COVID-19, while ensuring that the safety and wellbeing of our staff and the patients participating in our clinical trials has been and remains our top priority.

"The COVID-19 crisis has and will likely continue to delay clinical trials throughout the sector and as anticipated has impacted patient recruitment into BerGenBio clinical studies and extended previously anticipated timelines. The impact of the pandemic on our clinical trials has continued through the second quarter, but we are pleased that new patients continue to be recruited into our clinical studies with bemcentinib, and already enrolled patients have been able to continue their treatment throughout the restrictions.

"We continue to make progress, with a latest milestone in NSCLC trial presented at the Next Gen Immuno-Oncology Congress conference where 6 of the 7 identified AXL positive patients reported clinical benefit and data showed a 2.5-fold improvement in median Progression-free Survival.

"The Company remains in a strong cash position, with two drug candidates backed by pioneering biology, continued favourable clinical results and important data readouts on the horizon in two major cancer indications, as well as a potential COVID-19 treatment. This is an exciting time for us."

Operational Highlights – second quarter and the first half of 2020 (including post-period end)

Positive interim clinical and translational phase II data with bemcentinib in combination with KEYTRUDA in checkpoint inhibitor refractory NSCLC patients
In June, BerGenBio presented positive data from its Cohort B, stage 1, in the phase II trial evaluating bemcentinib in combination with KEYTRUDA in patients with advanced non-small cell lung cancer (NSCLC) and with confirmed progression on prior immune checkpoint therapy.
The trial included 12 evaluable patients for cAXL, BerGenBio’s proprietary composite-AXL (cAXL) immunohistochemistry biomarker. 7 of these 12 patients were cAXL-positive whereby 6 of these 7 patients reported clinical benefit and 2.5-fold improvement in mPFS.
BerGenBio also reported an update on Overall Survival data from Cohort A, where cAXL-positive patients reported 12-month Overall Survival of 79% and median Overall Survival of 17.3 months, whereas cAXL-negative reported 60% and 12.4 months respectively.
Data was presented at the NextGen Immuno-Oncology Congress, 25 June
First patient dosed in bemcentinib COVID-19 study in June 2020
In April, BerGenBio announced the selection of bemcentinib as the first candidate in a UK Government-backed national ACCORD study.
The study was a multicentre, seamless, Phase II adaptive randomisation platform trial to assess the efficacy and safety of multiple candidate agents for the treatment of COVID-19 in hospitalised UK NHS patients, and the first patient was dosed in June.
At the end of July, the incidence of COVID-19 in the UK had drastically reduced and the UK Research and Innovation’s (UKRI) decided to cease grant funding. Subsequently, the University Hospital Southampton NHS Trust notified all sites in the ACCORD programme to cease the recruitment of new patients into the trial for all candidate agents. Patients already recruited, including those dosed with bemcentinib, will continue on treatment as per the protocol.
The decision to halt the study reflected the significant decrease in the incidence of COVID-19 in the UK and difficulty recruiting a sufficient number of patients and in no way reflected any interpretation of the efficacy or safety of any of the candidate agents.
BerGenBio is now in the late stage set-up phase to sponsor a similar study to ACCORD in a country of high COVID-19 incidence.
First patient dosed in bemcentinib Glioblastoma study in July 2020 (post-period)
In July, BerGenBio announced the first patient was dosed in an investigator-initiated trial (IIT) assessing bemcentinib in recurrent glioblastoma (GBM). The study will enrol up to 20 recurrent GBM patients, at up to 15 sites in the USA.
Increased expression of the receptor tyrosine kinase AXL is significantly correlated with poor prognosis in GBM patients and preclinical data has suggested that bemcentinib may be a promising therapeutic agent for GBM, particularly in post-irradiation mesenchymal-transformed GBM tumors.
A comprehensive translational research programme will run in parallel with the clinical trial.
Q2 2020 Financial Highlights

(Figures in brackets = same period 2019 unless otherwise stated)

Revenue for the second quarter amounted to NOK 0.0 million (NOK 0.0 million) and for the six months ended 30 June NOK 0.0 million (NOK 8.7 million). The revenue in 2019 reflects clinical milestone payments from ADCT.
Total operating expenses for the second quarter amounted to NOK 64.7 million (NOK 52.0 million) and for the six months ended 30 June NOK 121.0 million (NOK 106.5 million). NOK 7.5 million (NOK – 2.5 million) of operating expenses was non cash accruals for option cost.
The operating loss for the quarter came to NOK 64.7 million (NOK 52.0 million) and for the six months ended 30 June NOK 121.0 million (NOK 97.8 million), reflecting the level of activity related to the clinical trials BerGenBio are conducting.
Cash and cash equivalents increased to NOK 828.4 million by 30 June (NOK 419.4 by 31 March 2020).
Private placement completed in May 2020, with gross proceeds NOK 520 million (including NOK 20 million from repair issue in July). Net proceeds to be used to take full advantage of clinical development opportunities stemming from the Company’s technology and to progress readiness for early commercialisation possibilities and general corporate purposes.
Presentation and Webcast Details

A presentation by BerGenBio’s senior management team will take place today at 10:00 am CET:

The second quarter report and presentation is available on the Company’s website in the Investors/Financial Reports section and a recording of the webcast will be made available shortly after the webcast has finished.