On May 4, 2022 PharmaMar (MSE:PHM) reported that it has submitted a conditional marketing authorization application to the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) (Press release, PharmaMar, MAY 4, 2022, View Source [SID1234613469]). The application is to seek approval for treatment with Zepzelca (lurbinectedin) in adult patients with metastatic Small Cell Lung Cancer (SCLC) who have progressed following prior platinum-based chemotherapy.

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This registration application is based on data from the Phase II basket trial with lurbinectedin, in monotherapy, for the treatment of SCLC. This is the same trial that was used for the conditional approval of lurbinectedin in the US for the same indication and whose results were presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper), ASCO (Free ASCO Whitepaper), meeting in June 2019.

Lurbinectedin received "Accelerated Approval" from the FDA in June 2020 for the treatment of adult patients with metastatic SCLC with disease progression and is already the standard of care in the US. In 2021, lurbinectedin also received marketing authorization in the United Arab Emirates, Canada, Australia and Singapore.

According to regulations, an accelerated authorization requires a confirmatory trial, so PharmaMar announced in December 2021 the start of a confirmatory Phase III clinical trial, LAGOON, evaluating lurbinectedin for the treatment of patients with recurrent SCLC, which will also be used to apply for registration in Europe.

On May 4, 2022 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported that financial results for the first quarter of 2022 and provided a business update (Press release, Regeneron, MAY 4, 2022, View Source [SID1234613468]).

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"Our strong first quarter performance was marked by top- and bottom-line growth, accompanied by R&D progress and continued investment in our pipeline," said Leonard S. Schleifer, M.D., Ph.D., President and Chief Executive Officer of Regeneron. "We continued to see substantial U.S. sales growth for EYLEA and Dupixent worldwide. We are well-positioned to reach even more patients with type 2 inflammatory disease through FDA priority review designations for Dupixent in children with atopic dermatitis and in adults and adolescents with eosinophilic esophagitis."

"Our business achieved strong revenue growth in the first quarter of 2022 as we continue to realize the benefits of our sustained R&D investment and our focus on commercial execution," said Robert E. Landry, Executive Vice President, Finance and Chief Financial Officer of Regeneron. "We remain confident that our differentiated products and significant pipeline opportunities position us well to deliver strong results and provide sustainable value to patients and shareholders."

Business Highlights

Key Pipeline Progress

Regeneron has approximately 35 product candidates in clinical development, including a number of marketed products for which it is investigating additional indications. Updates from the clinical pipeline include:

EYLEA (aflibercept) Injection

A supplemental Biologics License Application (sBLA) for EYLEA for an every-16-weeks dosing regimen in patients with non-proliferative diabetic retinopathy (NPDR) was submitted.
Aflibercept 8 mg

In February 2022, the Company announced detailed results from its Phase 2 trial evaluating an investigational 8 mg high dose of aflibercept compared to the currently-approved 2 mg dose of EYLEA in patients with neovascular age-related macular degeneration (wet AMD). The trial met its primary endpoints for safety, and no new safety signals were observed through week 44. Consistent with initial data announced last year, aflibercept 8 mg continued to show numeric improvements in anatomical and vision outcomes compared to EYLEA through 44 weeks.
Dupixent (dupilumab)

In April 2022, the European Commission (EC) approved Dupixent for the treatment of severe asthma in children aged 6 to 11 years.
The U.S. Food and Drug Administration (FDA) accepted for priority review the sBLA for Dupixent for children aged 6 months to 5 years with moderate-to-severe atopic dermatitis, with a target action date of June 9, 2022. A regulatory application was also submitted in the European Union (EU).
The FDA accepted for priority review the sBLA for Dupixent for adults and adolescents aged 12 years and older with eosinophilic esophagitis (EoE), with a target action date of August 3, 2022. A regulatory application was also submitted in the EU.
In January 2022, the Company and Sanofi announced positive results from a second Phase 3 trial in adults with uncontrolled prurigo nodularis. An sBLA and a regulatory submission in the EU for Dupixent for adults with uncontrolled prurigo nodularis were subsequently submitted.
In February 2022, the Company and Sanofi provided an update on Dupixent in patients with chronic spontaneous urticaria (CSU), in which they had previously reported positive results from the first trial in biologic-naïve patients (i.e., not previously treated with omalizumab) that showed Dupixent significantly reduced itch and hives compared to standard-of-care antihistamines alone. The Company and Sanofi announced that they stopped a second trial in patients refractory to omalizumab due to futility.
Antibodies to SARS-CoV-2 virus

In April 2022, the Company announced that the FDA extended by three months its review of the BLA for REGEN-COV (casirivimab and imdevimab) to treat COVID-19 in non-hospitalized patients and as prophylaxis in certain individuals. The extension is due to ongoing discussions with the FDA on pre-exposure prophylactic use, for which Regeneron has submitted additional data from its completed prophylaxis trial that the FDA has accepted for review. The FDA determined these additional data constitute a Major Amendment to the BLA and provided a new target action date of July 13, 2022.
A regulatory application was submitted in the EU for RonapreveTM(b) for the treatment of COVID-19 in hospitalized patients.
In January 2022, the FDA revised the Emergency Use Authorization (EUA) for REGEN-COV to exclude its use in geographic regions where, based on available information including variant susceptibility and regional variant frequency, infection or exposure is likely due to a variant such as an Omicron-lineage variant that is not susceptible to the treatment. If, in the future, patients in certain geographic regions are likely to be infected or exposed to a variant that is susceptible to REGEN-COV, then the limitation on use may be revised.
The Company is progressing investigational "next generation" antibodies that are active against multiple variants including those of Omicron-lineage, and has initiated a first-in-human clinical trial.
Fianlimab, an antibody to LAG-3

A Phase 3 study in first-line metastatic melanoma was initiated.
Odronextamab, a CD20xCD3 bispecific antibody

The FDA granted Fast Track designation for follicular lymphoma and diffuse large B-cell lymphoma.
NTLA-2001, a CRISPR/Cas9 therapeutic for TTR gene knockout

In February 2022, Intellia Therapeutics, Inc. and the Company reported updated positive interim data from the Phase 1 trial in transthyretin (ATTR) amyloidosis.
Business Development Update

In April 2022, the Company entered into a definitive merger agreement to acquire Checkmate Pharmaceuticals, Inc. at a total equity value of approximately $250 million. On May 2, 2022, the Company initiated a tender offer to acquire any and all outstanding shares of Checkmate common stock at a price of $10.50 per share, to be paid to each shareholder tendering Checkmate shares in cash, without interest, subject to reduction for any applicable withholding taxes. The transaction is expected to close, subject to the satisfaction of customary closing conditions including regulatory approvals, in mid-2022.
First Quarter 2022 Financial Results

Revenues

Total revenues increased by 17% to $2.965 billion in the first quarter of 2022, compared to $2.529 billion in the first quarter of 2021. Total revenues excluding REGEN-COV and Ronapreve(b) revenues for both periods increased by 25% to $2.749 billion in the first quarter of 2022, compared to the first quarter of 2021(a).

Net product sales recorded by the Company consist of the following:

Total revenues also include collaboration revenues(c) of $1.233 billion in the first quarter of 2022, compared to $754 million in the first quarter of 2021. Sanofi collaboration revenue increased primarily due to the Company’s share of profits from commercialization of antibodies, which were $415 million in the first quarter of 2022, compared to $261 million in the first quarter of 2021. The change in the Company’s share of profits from commercialization of antibodies was driven by higher Dupixent profits. In the first quarter of 2022, the Company earned a $50 million sales-based milestone from Sanofi, upon aggregate annual sales of antibodies outside the United States exceeding $2.0 billion on a rolling twelve-month basis.

Bayer collaboration revenue increased to $385 million in the first quarter of 2022, compared to $323 million in the first quarter of 2021.

The Company also recorded Roche collaboration revenue of $216 million for the first quarter of 2022, compared to $67 million in the first quarter of 2021, in connection with payments from Roche attributable to global gross profits from sales of Ronapreve.

Refer to Table 4 for a summary of collaboration revenue.

Other revenue in the first quarter of 2022 included a $30 million up-front payment received from Ultragenyx in connection with the Company’s Evkeeza license and collaboration agreement.

GAAP and non-GAAP R&D expenses increased in the first quarter of 2022, compared to the first quarter of 2021, primarily due to higher headcount and headcount-related costs, an increase in clinical manufacturing activities, and lower reimbursements from Roche related to REGEN-COV. The increase was partly offset by lower costs incurred in connection with REGEN-COV development activities.
Acquired IPR&D in the first quarter of 2022 included a $20 million opt-in payment in connection with a product candidate under the Company’s collaboration agreement with Adicet Bio, Inc.
The increase in GAAP and non-GAAP SG&A expenses in the first quarter of 2022, compared to the first quarter of 2021, was primarily due to higher headcount and headcount-related costs and an increase in commercialization-related expenses for EYLEA.
GAAP COGS in the first quarter of 2022 included $58 million of costs related to REGEN-COV, including inventory write-offs and reserves, as a result of the FDA revision of the EUA for REGEN-COV (as described above). GAAP and non-GAAP COGS in the first quarter of 2022 included lower REGEN-COV manufacturing costs since there were no net product sales in the United States.
COCM increased in the first quarter of 2022, compared to the first quarter of 2021, primarily due to the recognition of manufacturing costs associated with higher sales of Dupixent and an increase in shipments of commercial supplies of Praluent for Sanofi outside the United States.
Other Financial Information

GAAP other income (expense) included the recognition of net unrealized losses on equity securities of $211 million in the first quarter of 2022, compared to $144 million of net unrealized gains in the first quarter of 2021.

In the first quarter of 2022, the Company’s GAAP effective tax rate was 8.3%, compared to 11.0% in the first quarter of 2021. The decrease in the GAAP effective tax rate was due in part to the impact of stock-based compensation. In the first quarter of 2022, the non-GAAP effective tax rate was 11.6%, compared to 10.5% in the first quarter of 2021.

GAAP net income per diluted share was $8.61 in the first quarter of 2022, compared to $10.09 in the first quarter of 2021. Non-GAAP net income per diluted share was $11.49 in the first quarter of 2022, compared to $9.89 in the first quarter of 2021. A reconciliation of the Company’s GAAP to non-GAAP results is included in Table 3 of this press release.

During the first quarter of 2022, the Company repurchased shares of common stock under its share repurchase program, and recorded the cost of the shares received, or $352 million, as Treasury Stock. As of March 31, 2022, $2.493 billion remained available for share repurchases under the program.

Net cash provided by operating activities in the first quarter of 2022 was $2.102 billion, compared to $669 million in the first quarter of 2021, resulting in $1.960 billion in free cash flow for the first quarter of 2022, compared to $553 million for the first quarter of 2021. The increase in free cash flow in the first quarter of 2022 was primarily due to the Company’s collection of amounts due from the U.S. government in connection with REGEN-COV sales in the fourth quarter of 2021.

2022 Financial Guidance(d)

The Company’s full year 2022 financial guidance consists of the following components:

* GAAP and non-GAAP amounts are equivalent as no non-GAAP adjustments have been or are expected to be recorded.

** ETR guidance excludes the impact of the provision requiring capitalization and amortization of R&D expenses enacted as part of the Tax Cuts and Job Act (TCJA), as management’s current expectation is it will be deferred or repealed by Congress in 2022. If this provision of the TCJA is not deferred or repealed, the Company would expect its ETR to be lower than the guidance disclosed herein.

A reconciliation of full year 2022 GAAP to non-GAAP financial guidance is included below:

Conference Call Information

Regeneron will host a conference call and simultaneous webcast to discuss its first quarter 2022 financial and operating results on Wednesday, May 4, 2022, at 8:30 AM Eastern Time. Participants may access the conference call live via webcast on the "Investors and Media" page of Regeneron’s website at www.regeneron.com. To participate via telephone, please register in advance at View Source Upon registration, all telephone participants will receive a confirmation email detailing how to join the conference call, including the dial-in number along with a unique passcode and registrant ID that can be used to access the call. A replay of the conference call and webcast will be archived on the Company’s website for at least 30 days.

On May 4, 2022 G1 Therapeutics, Inc. (Nasdaq: GTHX), a commercial-stage oncology company, reported that financial update for the first quarter ended March 31, 2022 (Press release, G1 Therapeutics, MAY 4, 2022, View Source [SID1234613467]).

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"The first quarter of 2022 was a period of transition and execution across the G1 business," said Jack Bailey, Chief Executive Officer of G1 Therapeutics. "In March of this year, we entered a new phase for COSELA promotion as we transitioned fully away from our commercial launch partner Boehringer Ingelheim and put the promotion of COSELA into the hands of our newly deployed G1 sales team; the strong month over month sales performance in March adds to the evidence of good early access to key accounts by our team. Our sales and commercial teams are now fully engaged in driving depth in key top organizations. Regarding our clinical programs, we are approaching a data-rich period, as we currently expect initial results from each of our ongoing Phase 2 and Phase 3 trials over the coming 18 months, starting with data from our three Phase 2 trials in the fourth quarter of this year."

First Quarter 2022 and Recent Highlights

Financial

Achieved Total Revenue of $6.9 Million: G1 recognized total revenues of $6.9 million in the first quarter of 2022, including $5.5 million in net product revenue from sales of COSELA.
Ended the First Quarter 2022 with Cash and Cash Equivalents of $183.0 Million: The Company’s current financial position is expected to be sufficient to fund G1’s operations and capital expenditures into 2024.
Commercial

Fully Deployed COSELA Sales Team: On March 2, 2022, the co-promotion agreement for COSELA between G1 and Boehringer Ingelheim was terminated. As of February 15, 2022, G1 had fully deployed its sales team into regions across the U.S. to accelerate sales activities and help maximize the adoption of COSELA.
Clinical

Reiterated Expectation of Initial Data in the Fourth Quarter of 2022 from Three Phase 2 Trials of Trilaciclib: G1 has reiterated that it expects to release initial data from multiple ongoing Phase 2 clinical trials of trilaciclib in the fourth quarter of 2022. These trials include a Phase 2 trial of trilaciclib in combination with avelumab in bladder cancer; a Phase 2 trial in combination with the antibody-drug conjugate (ADC) Trodelvy (sacituzumab govitecan-hziy) in patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC); and a Phase 2 trial designed to confirm the mechanism of action of trilaciclib in modulating the anti-tumor immune response with and without a checkpoint inhibitor in early stage TNBC.
Reiterated Expectation of Initial Data in 2023 from Two Phase 3 Trials of Trilaciclib: G1 expects to release data from two ongoing pivotal Phase 3 clinical trials of trilaciclib in 2023. Initial results including myeloprotection and Objective Response Rate (ORR) endpoints from PRESERVE 1, our ongoing line extension trial of trilaciclib in patients with colorectal cancer (CRC) receiving first line trilaciclib or placebo administered prior to FOLFOXIRI and bevacizumab, are expected in the first quarter of 2023. Initial results including interim results for Overall Survival (OS) from PRESERVE 2, our ongoing line extension trial of trilaciclib in PD-L1 positive and negative patients with TNBC receiving first line gemcitabine and carboplatin, are expected in the second half of 2023.
Medical

Presented New Real-World Data at the Annual Conference of the National Comprehensive Cancer Network (NCCN) Showing the Impact of Trilaciclib on Hospitalizations and the Burden of Myelosuppression in Patients with ES-SCLC Treated with Chemotherapy: Results showed that the use of trilaciclib prior to chemotherapy was associated with a 50% reduction in the percent of patients with grade ≥ 3 myelosuppressive hematologic adverse events in at least one blood cell lineage and a 74% reduction in the percent of all-cause hospitalizations (days 1 to 21 after treatment), compared to patients who received chemotherapy alone. The analyses were derived using structured, real-world, de-identified clinical patient level data from the Integra Connect oncology warehouse. (Press release here)
Published Data in Cancer Treatment and Research Communications Showing Treatment Patterns and the Burden of Myelosuppression for Patients with Small Cell Lung Cancer (SCLC): Results of this retrospective study showed that 42 percent of small-cell lung cancer patients failed to complete the recommended number of chemotherapy cycles, and 74 percent of patients were admitted to the hospital due to a myelosuppressive event, thus underscoring the burden of myelosuppression. Additionally, health care resource utilization associated with myelosuppression was prominent, suggesting a substantial burden on older patients with SCLC. These data were derived from a descriptive, retrospective study of patients with SCLC aged ≥65 years, identified from linked Surveillance, Epidemiology, and End Results (SEER)-Medicare data. (Publication available here)
Corporate

Strategic Decision Made to Discontinue the Rintodestrant Program: After completing our evaluation of the rintodestrant partnering options and recent data in the highly competitive oral SERD space, G1 has made the strategic decision to discontinue the program, including all clinical and partnering efforts. G1 will responsibly wind down all remaining clinical efforts for rintodestrant by the end of this year and revert the rights back to the originator (University of Illinois Chicago); there are no additional financial obligations due to the originator resulting from the reversion.
First Quarter 2022 Financial Results

As of March 31, 2022, cash and cash equivalents totaled $183.0 million, compared to $221.2 million as of December 31, 2021.

Total revenues for the first quarter of 2022 were $6.9 million, including $5.5 million in net product sales of COSELA and license revenue of $1.4 million. This license revenue is primarily related to clinical trial reimbursements from EQRx and Simcere.

Operating expenses for the first quarter of 2022 were $53.7 million, compared to $39.8 million for the first quarter of 2021. GAAP operating expenses include stock-based compensation expense of $5.8 million for the first quarter of 2022, compared to $5.9 million for the first quarter of 2021.

Cost of goods sold expense for the first quarter of 2022 were $0.7 million compared to $0.2 for the first quarter of 2021. The increase is related to the Company’s period costs for the sales of COSELA, including third-party logistics costs for the sales of COSELA, inventory overhead costs, and personnel costs.

Research and development (R&D) expenses for the first quarter of 2022 were $26.3 million, compared to $16.5 million for the first quarter of 2021. The increase in R&D expenses was driven by an increase in clinical trial spend related to increased activity in all of our clinical trials including an acceleration of enrollment in our Phase 3 CRC trial, which is partially offset by a decrease in costs associated with the manufacturing of active pharmaceutical ingredients and drug product to support clinical trials.

Selling, general, and administrative (SG&A) expenses for the first quarter of 2022 were $26.7 million, compared to $23.0 million for the first quarter of 2021. The increase in SG&A expenses was largely due to an increase in personnel costs due to increased headcount, and an increase in professional services, insurance and other administrative costs.

The net loss for the first quarter of 2022 was $49.2 million, compared to $26.4 million for the first quarter of 2021. The basic and diluted net loss per share for the first quarter of 2022 was $(1.15) compared to $(0.65) for the first quarter of 2021.

Financial Guidance

G1 expects its current cash position of $183.0 million to be sufficient to fund its operations and capital expenditures into 2024.

Webcast and Conference Call

G1 will host a webcast and conference call at 8:30 a.m. ET today to provide a corporate and financial update for the first quarter 2022 ended March 31, 2022. The live call may be accessed by dialing (866) 763-6020 (domestic) or (409) 216-0626 (international) and entering the conference code: 2229795. A live and archived webcast will be available on the Events & Presentations page of the company’s website: www.g1therapeutics.com. The webcast will be archived on the same page for 90 days following the event.

About COSELA (trilaciclib) for Injection

COSELA (trilaciclib) was approved by the U.S. Food and Drug Administration on February 12, 2021.

Indication
COSELA (trilaciclib) is indicated to decrease the incidence of chemotherapy-induced myelosuppression in adult patients when administered prior to a platinum/etoposide-containing regimen or topotecan-containing regimen for extensive-stage small cell lung cancer.

Important Safety Information
COSELA is contraindicated in patients with a history of serious hypersensitivity reactions to trilaciclib.

Warnings and precautions include injection-site reactions (including phlebitis and thrombophlebitis), acute drug hypersensitivity reactions, interstitial lung disease (pneumonitis), and embryo-fetal toxicity.

The most common adverse reactions (>10%) were fatigue, hypocalcemia, hypokalemia, hypophosphatemia, aspartate aminotransferase increased, headache, and pneumonia.

This information is not comprehensive. Please click here for full Prescribing Information. View Source

To report suspected adverse reactions, contact G1 Therapeutics at 1-800-790-G1TX or call FDA at 1-800-FDA-1088 or visit www.fda.gov/medwatch.

On March 4, 2022 AstraZeneca reported it’s supplemental Biologics License Application (sBLA) for Imfinzi (durvalumab), in combination with standard-of-care chemotherapy, has been accepted and granted Priority Review in the US for patients with locally advanced or metastatic biliary tract cancer (BTC) (Press release, AstraZeneca, MAY 4, 2022, View Source [SID1234613466]).

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The Food and Drug Administration (FDA) grants Priority Review to applications for medicines that, if approved, would offer significant improvements over available options by demonstrating safety or efficacy improvements, preventing serious conditions, or enhancing patient compliance.1 The Prescription Drug User Fee Act date, the FDA action date for their regulatory decision, is during the third quarter of 2022.

BTC is a group of rare and aggressive cancers that occur in the bile ducts and gallbladder. 2,3 Approximately 23,000 people in the US are diagnosed with BTC each year.2 These patients have a poor prognosis, with approximately 5% to 15% of patients with BTC surviving five years.4

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: "People with advanced biliary tract cancer have faced poor outcomes and limited treatment options for too long, and today’s news for the TOPAZ-1 trial underscores the urgency to deliver new, effective therapies in this setting. We are working closely with the FDA to bring the first immunotherapy-based option to patients with this devastating cancer and potentially set a new standard of care with Imfinzi plus chemotherapy."

The sBLA was based on results from an interim analysis of the TOPAZ-1 Phase III trial presented during the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers (ASCO GI) Symposium. The data showed Imfinzi plus chemotherapy (gemcitabine plus cisplatin) reduced the risk of death by 20% versus chemotherapy alone (based on a hazard ratio [HR] of 0.80; 95% confidence interval [CI], 0.66-0.97; 2-sided p=0.021). An estimated one in four (25%) patients treated with Imfinzi plus chemotherapy were alive at two years compared to one in 10 (10%) treated with chemotherapy alone.

Results also showed a statistically significant 25% reduction in the risk of disease progression or death with Imfinzi plus chemotherapy (HR, 0.75; 95% CI, 0.64-0.89; 2-sided p=0.001). The Imfinzi combination was generally well tolerated and did not increase the discontinuation rate due to adverse events compared to chemotherapy alone.

In December 2020, Imfinzi was granted Orphan Drug Designation in the US for the treatment of BTC.

Notes

Biliary tract cancer
Biliary tract cancer (BTC) is a group of rare and aggressive gastrointestinal (GI) cancers that form in the cells of the bile ducts (cholangiocarcinoma), gallbladder or ampulla of Vater (where the bile duct and pancreatic duct connect to the small intestine).2,3

Cholangiocarcinoma is more common in China and South-East Asia and is on the rise in Western countries.2,4 Gallbladder cancer is more common in certain regions of South America, India and Japan.5

Early-stage BTC affecting the bile ducts and gallbladder often presents without clear symptoms and most new cases of BTC are therefore diagnosed at an advanced stage, when treatment options are limited and the prognosis is poor.4-6

TOPAZ-1
TOPAZ-1 is a randomised, double-blind, placebo controlled, multicentre, global Phase III trial of Imfinzi in combination with chemotherapy (gemcitabine plus cisplatin) versus placebo in combination with chemotherapy as a 1st-line treatment in 685 patients with unresectable advanced or metastatic BTC including intrahepatic and extrahepatic cholangiocarcinoma, and gallbladder cancer. Patients with ampullary carcinoma were excluded.

The primary endpoint is overall survival and key secondary endpoints included progression-free survival, objective response rate and safety. The trial was conducted in 105 centres across 17 countries including in the US, Europe, South America and several countries in Asia including South Korea, Thailand, Japan and China.

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

Imfinzi is the only approved immunotherapy in the curative-intent setting of unresectable, Stage III non-small cell lung cancer (NSCLC) in patients whose disease has not progressed after chemoradiotherapy, and is the global standard of care in this setting based on the PACIFIC Phase III trial.

Imfinzi is also approved in the US, EU, Japan, China and many other countries around the world for the treatment of extensive-stage small cell lung cancer (ES-SCLC) based on the CASPIAN Phase III trial. In 2021, updated results from the CASPIAN trial showed Imfinzi plus chemotherapy tripled patient survival at three years versus chemotherapy alone.

Imfinzi is also approved for previously treated patients with advanced bladder cancer in several countries.

Since the first approval in May 2017, more than 100,000 patients have been treated with Imfinzi.

As part of a broad development programme, Imfinzi is being tested as a single treatment and in combinations with other anti-cancer treatments for patients with small cell lung cancer (SCLC), NSCLC, bladder cancer, several GI cancers, ovarian cancer, endometrial cancer, and other solid tumours.

In the past year, Imfinzi combinations have demonstrated clinical benefit in multiple additional cancer settings with positive Phase III trials in unresectable advanced liver cancer (HIMALAYA) and metastatic NSCLC (POSEIDON).

AstraZeneca in GI cancers
AstraZeneca has a broad development programme for the treatment of GI cancers across several medicines and a variety of tumour types and stages of disease. In 2020, GI cancers collectively represented approximately 5.1 million new cancer cases leading to approximately 3.6 million deaths.6

Within this programme, the Company is committed to improving outcomes in gastric, liver, BTC, oesophageal, pancreatic, and colorectal cancers.

Imfinzi is being assessed in combinations in liver, BTC, oesophageal and gastric cancers in an extensive development programme spanning early to late-stage disease.

The Company aims to understand the potential of Enhertu (trastuzumab deruxtecan), a HER2-directed antibody drug conjugate, in the two most common GI cancers, colorectal and gastric cancers. Enhertu is jointly developed and commercialised by AstraZeneca and Daiichi Sankyo.

Lynparza (olaparib) is a first-in-class PARP inhibitor with a broad and advanced clinical trial programme across multiple GI tumour types including pancreatic and colorectal cancers. Lynparza is developed and commercialised in collaboration with MSD (Merck & Co., Inc. inside the US and Canada).

AstraZeneca in immunotherapy
Immunotherapy is a therapeutic approach designed to stimulate the body’s immune system to attack tumours. The Company’s Immuno-Oncology (IO) portfolio is anchored in immunotherapies that have been designed to overcome evasion of the anti-tumour immune response. 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 single treatment and in combination with tremelimumab and other novel antibodies in multiple tumour types, stages of disease, and lines of treatment, 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, and targeted small 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 is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients.

The Company’s focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyse changes in the practice of medicine and transform the patient experience.

AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death.

On May 4, 2022 BerGenBio ASA (OSE:BGBIO), a clinical-stage biopharmaceutical company developing novel, selective AXL inhibitors for severe unmet medical needs, reported an update on its business strategy (Press release, BerGenBio, MAY 4, 2022, View Source [SID1234613465]). BerGenBio will now focus on two key indications; 1st line non-small cell lung cancer (NSCLC) and COVID-19, which the Company believes offer the optimal path towards translating BerGenBio’s strong scientific foundation into significant value generation from marketed products to address unmet medical needs.

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The opportunity

BerGenBio has for many years pioneered research into AXL inhibition, with its lead development candidate bemcentinib showing clinical potential in oncology and infectious disease. With over 600 patients dosed (approx. 400 in oncology and approx. 200 in COVID-19), the Company has built a large dataset demonstrating biological and clinical activity while simultaneously defining dosing regimens to identify an appropriate balance of safety and efficacy.

The updated business strategy announced today builds on bemcentinib’s mode of action and data gathered from a broad clinical exploration to progress two distinct opportunities with the potential to significantly improve the lives of patients: NSCLC and COVID-19. Both indications show strong evidence of bemcentinib activity, with the advantage of accumulation in target organs, options for accelerated registration, compelling competitive advantages, and both represent high unmet medical needs.

Martin Olin, Chief Executive Officer of BerGenBio, commented: "BerGenBio has been at the forefront of understanding of AXL biology and, having pioneered this area, we remain confident that selective AXL inhibition holds significant potential as a transformative treatment modality for several serious diseases. A rapidly evolving treatment landscape, with improved standards of care in areas such as oncology requires BerGenBio to be nimble and identify specific opportunities where we can address unmet needs in a competitive manner.

With this in mind we believe that by introducing a laser focus and rightsizing the organization on two key areas where we see our pipeline has the greatest impact, we are efficiently advancing BerGenBio’s potential; building on our strong scientific foundation to deliver new drugs to market resulting in better outcomes for patients and the generation of significant value for our shareholders."

NSCLC

Despite advances in treatment, lung cancer remains the leading cause of cancer-related deaths throughout the world. Approximately 85% of lung cancers are classified as NSCLC. BerGenBio is targeting 1st Line STK11 mutated Non-Squamous NSCLC patients, an extremely large patient population with very limited response to the standard of care treatments. STK11 is an important tumor suppressor gene reported to confer immunotherapy resistance in NSCLC and is present in up to 20% of NSCLC patients.

Pre-clinical and clinical studies have suggested a mechanism by which bemcentinib may restore response to immune checkpoint inhibitor therapy and enable the avoidance of chemoresistance in NSCLC patients harboring STK11 mutations, thus potentially offering a treatment option to those patients who respond poorly to existing therapies. Data from the subset of STK11mutated patients treated in the Company’s BGB008 study in 2nd line NSCLC also provides early indications of efficacy in this biomarker driven patient population.

The FDA has recognized that STK11 is currently a "non-actionable" mutation – one that confers poor outcome and has no specific therapeutic approaches today and have granted BerGenBio a Fast Track Designation for bemcentinib in this setting. To date, bemcentinib is to the Company’s knowledge the only selective AXL inhibitor in development for patients with STK11 mutation. BerGenBio has a strong proprietary position for treatment of this population and believes there may be a potential for an accelerated approval pathway in this patient sub-set.

COVID-19

Despite the success of vaccines, there is still a large number of hospitalized patients that remain in need of improved therapeutic options for COVID-19. Research into bemcentinib’s potential in hospitalized COVID-19 patients began in 2020, in response to the emergence of the pandemic, and based on the Company’s understanding of AXL’s role in mediating aggressive diseases.

Recently, BerGenBio announced results from the Phase II sub-protocol of the platform ACCORD2 study, which met its primary and key secondary endpoints, with demonstrable efficacy in patients on top of current standard-of-care treatments including remdesivir and corticosteroids. Further, bemcentinib has been selected to be studied under the EUSolidAct platform trial through a sub-protocol enrolling 500 patients across European sites. Given the ongoing need for new treatment options for hospitalized COVID-19 patients, the novel mechanism of action of bemcentinib (independent of the spike protein), along with potential to confirm the ACCORD2 data in the EUSolidAct trial, the Company believes that this could warrant Emergency Use Authorizations based on precedents.

The Company believes that the unique mechanism of action and properties of bemcentinib positions it well as a novel treatment modality within severe respiratory infections beyond COVID-19.

With a focused strategy and rightsized organization BerGenBio plans to unlock significant potential value related to the two indications selected and define the path to market.