On May 5, 2022 BioCryst Pharmaceuticals, Inc. (Nasdaq:BCRX) reported financial results for the first quarter ended March 31, 2022, and provided a corporate update (Press release, BioCryst Pharmaceuticals, MAY 5, 2022, View Source [SID1234613611]).

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"We are now over a year into the ORLADEYO launch and are excited to see strong and continuing patient demand and steady expansion in our prescriber base among both new and existing prescribers. These trends continued in the first quarter of 2022 and reinforce our confidence that we will achieve no less than $250 million in net ORLADEYO revenue in 2022 and peak ORLADEYO sales of $1 billion," said Jon Stonehouse, president and chief executive officer of BioCryst.

"We also have made substantial progress in our investigation with BCX9930. Based on our initial findings, we believe that both dose and dosing regimen could be contributing factors to the safety signal we have observed. By the end of the third quarter, we plan to discuss our proposed approach to resume the REDEEM trials, under a revised dosing protocol, with regulators," Stonehouse added.

Program Updates and Key Milestones

ORLADEYO (berotralstat): Oral, Once-daily Treatment for Prevention of Hereditary Angioedema (HAE) Attacks

U.S. Launch

ORLADEYO net revenue in the first quarter of 2022 was $49.7 million.
Approximately 50 percent of patients currently on ORLADEYO have switched from another prophylactic therapy, and half of those patients have come from lanadelumab. These trends continued with new patients starting ORLADEYO in Q1 2022.
In the first quarter, new patient prescriptions were evenly split between repeat prescribers and new prescribers, with an approximately equal number of new prescriptions coming from the top 500 HAE treaters and the broader set of other HAE treaters.
The company has completed its latest quarterly survey of another 60 allergists who treat an average of eight HAE patients. These physicians were already using ORLADEYO on 13 percent of their patients and predicted growth to 23 percent over the next 12 months. These findings were in line with previously reported market research from August 2021.
Approximately 80 percent of HAE patients in the U.S. are insured by payors and pharmacy benefit managers that cover ORLADEYO. Despite prior authorization headwinds early in 2022, approximately 80 percent of patients on ORLADEYO were receiving paid product by the end of the first quarter, a substantial increase from approximately 66 percent of patients in the second half of 2021.
Most patients are well-controlled on ORLADEYO and remain on therapy. Once payor prior authorization is complete, 78 percent of patients switching from lanadelumab and 73 percent of patients switching from subcutaneous C1 inhibitor remain on ORLADEYO for at least six months. About 70 percent of all patients who receive reimbursed product stay on ORLADEYO for at least 12 months, compared to 60 percent of patients who remain on long-term free product.
The company expects steady quarterly ORLADEYO net revenue growth throughout the remainder of 2022, with total 2022 ORLADEYO net revenue of no less than $250 million.
"We are very pleased that strong patient demand continued to drive growth in the first quarter and overcome the traditional Q1 reimbursement headwinds. With outstanding reimbursement in place, patients continuing to enjoy an excellent experience on ORLADEYO and the expansion of both our new and existing prescriber bases, we expect steady growth throughout the remainder of 2022 as we achieve no less than $250 million in ORLADEYO net revenues for the year," said Charlie Gayer, chief commercial officer of BioCryst.

ORLADEYO: Global Updates

ORLADEYO has been launched in Denmark, France, Germany, Japan, Norway, Sweden, the United Arab Emirates and the United Kingdom. The company expects launches in additional countries throughout the year.
Complement Oral Factor D Inhibitor Program – BCX9930

On April 8, 2022, BioCryst announced that the company was voluntarily pausing enrollment in BCX9930 clinical trials while it investigated observed elevations in serum creatinine seen in some patients.

Patients in the REDEEM-1, REDEEM-2 and RENEW clinical trials randomized to BCX9930 began those trials by starting immediately at a dose of 500 mg twice-daily. Patients receiving BCX9930 in the long-term extension trial started at lower doses as part of the proof-of-concept dose escalation regimen and were ultimately moved up to 500 mg twice-daily.

Preliminary evidence from the investigation points to both the 500 mg twice-daily dosing level and the immediate start of that dose, without a period at a lower dose first, as plausible contributory factors for the observed increases in serum creatinine.

Based on the initial results of the investigation, and the safety and efficacy data observed in the BCX9930 clinical program at 400 mg twice-daily, the company plans to discuss with regulators whether clinical trials with amended protocols could resume using stepped dosing to 400 mg twice-daily. The company expects to have discussions with regulators by the end of the third quarter.

During the ongoing investigation the company has observed the following:

Three patients with PNH receiving BCX9930 in the REDEEM trials had early onset, and moderate or severe, elevations in their serum creatinine (2-4 xULN) after several weeks of dosing with 500 mg twice-daily. Two of these patients have been discontinued from therapy and one patient (who had the smallest increase in serum creatinine) continues on BCX9930 at this time.
The company estimates that one-third of subjects randomized to BCX9930 in the REDEEM studies have had early increases in serum creatinine.
The company also found a different pattern of slowly evolving, late onset, mild to moderate increases in serum creatinine in approximately 40 percent of patients in the long-term extension of the proof-of-concept trial, after those patients switched to the 500 mg twice-daily dose. This pattern was not observed during treatment with doses lower than 500 mg.
Subsequent to BioCryst voluntarily pausing trial enrollments, the U.S. Food and Drug Administration (FDA) informed the company that it has placed the clinical program for BCX9930 on a partial clinical hold. Consistent with BioCryst’s voluntary action, the company may not enroll new patients in its BCX9930 clinical trials, however patients already enrolled who are receiving clinical benefit from BCX9930 treatment, and have no other available treatment options, can continue to be dosed and remain in the trials.

"As we complete our investigation, we will continue to be comprehensive and deliberate, with a primary focus on patient safety. After consultation with regulators, we will determine the next step for the BCX9930 program," said Dr. William Sheridan, Chief Medical Officer of BioCryst.

The company does not plan to provide additional updates on the BCX9930 program until it completes additional regulatory discussions and has more clarity on the next steps for the program.

Additional Updates

On February 8, 2022, the company announced the appointment of Machelle Sanders to its board of directors.
First Quarter 2022 Financial Results

For the three months ended March 31, 2022, total revenues were $49.9 million, compared to $19.1 million in the first quarter of 2021 (+161.3 percent year-over-year (y-o-y)). The increase was primarily due to $49.7 million in ORLADEYO net revenue in the first quarter of 2022, compared to $10.9 million in ORLADEYO net revenue in the first quarter of 2021 (+356.0 percent y-o-y).

Research and development (R&D) expenses for the first quarter of 2022 increased to $65.4 million from $42.4 million in the first quarter of 2021 (+54.2 percent y-o-y), primarily due to increased investment in the development of our Factor D program, including BCX9930, as well as other research, preclinical and development costs.

Selling, general and administrative (SG&A) expenses for the first quarter of 2022 increased to $34.3 million, compared to $22.1 million in the first quarter of 2021 (+55.2 percent y-o-y). The increase was primarily due to increased investment to support the commercial launch of ORLADEYO and expanded international operations.

Interest expense was $23.8 million in the first quarter of 2022, compared to $12.9 million in the first quarter of 2021 (+84.5 percent y-o-y). The increase was due to service on the royalty financings, which were completed in November 2021.

Net loss for the first quarter of 2022 was $74.2 million, or $0.40 per share, compared to a net loss of $64.3 million, or $0.36 per share, for the first quarter of 2021.

Cash, cash equivalents, restricted cash and investments totaled $446.8 million at March 31, 2022, compared to $244.4 million at March 31, 2021. Operating cash use for the first quarter of 2022 was $71.0 million.

Financial Outlook for 2022

Based on the strength of the ORLADEYO launch, and continued steady growth from new patient demand anticipated throughout the year, the company expects full year 2022 net ORLADEYO revenue to be no less than $250 million.

The company had previously expected operating expenses for full year 2022, not including non-cash stock compensation, to be between $440 million to $480 million. Once the company completes its investigation into BCX9930 and has clarity on the next step for the program it expects to provide an updated outlook on full year 2022 operating expenses. If BCX9930 program enrollment resumes, then operating expenses are likely to be at the lower end of the previously provided range. If we discontinue the BCX9930 program, then operating expenses for the year would be lower than that.

Conference Call and Webcast

BioCryst management will host a conference call and webcast at 8:30 a.m. ET today to discuss the financial results and provide a corporate update. The live call may be accessed by dialing 877-303-8027 for domestic callers and 760-536-5165 for international callers and using conference ID # 9498023. A live webcast of the call and any slides will be available online at the investors section of the company website at www.biocryst.com. A telephone replay of the call will be available by dialing 855-859-2056 for domestic callers or 404-537-3406 for international callers and entering the conference ID # 9498023.

On May 5, 2022 Bicycle Therapeutics plc (NASDAQ: BCYC), a biotechnology company pioneering a new and differentiated class of therapeutics based on its proprietary bicyclic peptide (Bicycle) technology, reported financial results for the first quarter ended March 31, 2022 and provided recent corporate updates (Press release, Bicycle Therapeutics, MAY 5, 2022, View Source [SID1234613610]).

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"We have made significant progress recently across our oncology pipeline," said Kevin Lee, Ph.D., Chief Executive Officer of Bicycle Therapeutics. "We reported interim data for the Phase I portion of the Phase I/II trial in BT8009, showing an overall response rate, or ORR, of 50% in the 5mg/m2 weekly cohort in patients with urothelial cancer and an encouraging tolerability profile. We believe BT8009 has the potential to offer clinically meaningful differentiation compared to currently available therapies and we look forward to advancing the program once the dose escalation phase is complete. We also look forward to initiating the BT5528 Phase II expansion cohorts soon."

Dr. Lee continued: "Beyond our Bicycle Toxin Conjugates, or BTCs, we continue to be encouraged as we progress our Bicycle TICA programs forward, including BT7480, which is advancing in the dose escalation portion of the Phase I clinical trial. Underscoring our efforts is a strong balance sheet and we anticipate our cash and cash equivalents will provide financial runway through 2024."

First Quarter 2022 and Recent Highlights

Announced Interim BT8009 Phase I Clinical Trial Results at the 2022 American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting. In April 2022, Bicycle announced interim Phase I results from the Phase I/II trial of BT8009, a second-generation BTC targeting Nectin-4. As of March 7, 2022, thirty-seven patients have been dosed in the Phase I/II trial of BT8009. A total of twelve response evaluable urothelial cancer (UC) patients have been dosed in monotherapy cohorts of 2.5mg/m2 and 5.0mg/m2 weekly in the ongoing trial. Four response evaluable UC patients were dosed at 2.5mg/m2 weekly, with one patient observed to have tumor reductions constituting a confirmed partial response (PR) and two patients observed to have stable disease (SD). Eight response evaluable UC patients were dosed at 5.0mg/m2 weekly, with four patients observed to have a confirmed complete response (CR) or PR, including one patient with a CR and three patients with a PR, and two patients with SD, reflecting a 50% ORR and 75% disease control rate. The median duration of response has not yet been reached in either the 2.5 mg/m2 or 5.0mg/m2 cohort, with four of the five responders in these cohorts still on therapy after at least 24 weeks, and a tolerability profile that remains consistent with earlier results from this trial.

Exploration of additional doses and frequencies continues, and Bicycle intends to provide further updates this year.
Announced Updated Preclinical Data on SARS-CoV-2 Antivirals at the 2022 Microbiology Society Annual Meeting. Bicycle created a wide range of <10kDa molecules with high binding affinity to the SARS-CoV-2 spike protein and then tested them in partnership with researchers at the Medical Research Council Laboratory of Molecular Biology. They were shown to be highly active in vitro at preventing SARS-CoV-2 infection of human cells. These compounds were further tested in partnership with experts at the University of Liverpool and shown to be highly potent when administered in vivo to rodent models of SARS-CoV-2 infection. These molecules have also been shown to be active in vitro across many of the SARS-CoV-2 variant strains, including Alpha, Beta, Delta and Omicron.
Financial Results

Cash and cash equivalents were $407.4 million as of March 31, 2022, compared to $438.7 million as of December 31, 2021. The decrease in cash is primarily due to cash used in operating activities.
Research and development expenses were $14.3 million for the three months ended March 31, 2022, compared to $9.7 million for the three months ended March 31, 2021. The increase in expense of $4.6 million was primarily due to increased discovery and platform-related expenses, as well as increased personnel-related expenses, including $1.2 million of incremental non-cash share-based compensation expense.
General and administrative expenses were $17.0 million for the three months ended March 31, 2022, compared to $8.1 million for the three months ended March 31, 2021. The increase of $8.9 million for the three months ended March 31, 2022 as compared to the same period in the prior year was primarily due to $5.2 million incremental non-cash share-based compensation expense, personnel-related costs and increased professional and consulting costs.
Net loss was $27.6 million, or $(0.93) basic and diluted net loss per share, for the three months ended March 31, 2022, compared to net loss of $16.2 million, or $(0.73) basic and diluted net loss per share, for three months ended March 31, 2021.

On May 5, 2022 Aulos Bioscience, an immuno-oncology company working to revolutionize cancer care through the development of potentially best-in-class IL-2 therapeutics, reported it has dosed the first patient in a Phase 1/2 clinical trial of AU-007 for the treatment of solid tumors (Press release, Aulos Bioscience, MAY 5, 2022, View Source [SID1234613609]). AU-007 is a human monoclonal antibody computationally designed by Biolojic Design, with a highly differentiated approach to harnessing the power of interleukin-2 (IL-2) to eradicate solid tumors.

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"We are very pleased to begin patient dosing in our Phase 1/2 trial of AU-007, as it marks a significant milestone in our advancement to a clinical-stage company," said Aron Knickerbocker, Aulos Bioscience’s chief executive officer. "This rapid progress speaks to the strength of our team at Aulos to collaborate efficiently and successfully move our first investigational therapy into the clinic. AU-007 has a mechanism of action completely distinct from anything ever tested in a human clinical trial, and we believe it addresses the key challenges associated with the therapeutic application of IL-2."

Currently approved therapy requires high doses of IL-2 that is associated with frequent and dangerous toxicities, including increased risk of pulmonary edema and capillary leakage. In preclinical studies, AU-007 has been shown to block IL-2 from binding to CD25 in trimeric receptors while preserving IL-2’s binding to dimeric CD122/CD132 receptors. This unique mechanism of action allows for anti-cancer activity from immune effector activation while preventing immunosuppressive T regulatory (Treg) cell expansion and vascular leakage driven by IL-2. Recently released preclinical data demonstrate significant tumor growth inhibition in murine models with AU-007, and complete MC38 colorectal tumor elimination when AU-007 is dosed in combination with checkpoint inhibitors.

The Phase 1/2 trial is a two-part, open label, first-in-human study currently enrolling patients in Australia. The study evaluates the safety, tolerability and immunogenicity of AU-007 in patients with unresectable locally advanced or metastatic cancer. Phase 1 consists of three dose escalation arms that evaluate AU-007 either as a monotherapy, in combination with a single loading dose of aldesleukin, or with both AU-007 and aldesleukin administered once every two weeks. The Phase 2 portion of the trial evaluates a dosing regimen selected from dose escalation for expansion in specified tumor types to further define the safety and initial efficacy of AU-007. Initial data from the Phase 1 portion of the clinical trial is anticipated in late 2022.

To learn more about the clinical trial program, please visit ClinicalTrials.gov, using the identifier NCT05267626.

About AU-007

AU-007 is a computationally designed, human IgG1 monoclonal antibody that is highly selective to the CD25-binding portion of IL-2. With a mechanism of action unlike any other IL-2 therapeutic in development, AU-007 leverages IL-2 to reinforce anti-tumor immune effects. This is achieved by preventing IL-2, either exogenous or secreted by T effector cells, from binding to trimeric receptors on T regulatory cells while still allowing IL-2 to bind and expand T effector and NK cells. This prevents the negative feedback loop caused by other IL-2-based treatments and biases the immune system toward activation over suppression. AU-007 also prevents IL-2 from binding to trimeric receptors on vasculature and pulmonary endothelium, which may significantly reduce the vascular leak syndrome and pulmonary edema associated with high-dose IL-2 therapy.

On May 5, 2022 AstraZeneca and Daiichi Sankyo’s Enhertu (trastuzumab deruxtecan) reported that it has been approved in the US for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received a prior anti-HER2-based regimen either in the metastatic setting, or in the neoadjuvant or adjuvant setting and have developed disease recurrence during or within six months of completing therapy (Press release, AstraZeneca, MAY 5, 2022, View Source [SID1234613608]).

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Enhertu is a specifically engineered HER2-directed antibody drug conjugate (ADC) being jointly developed and commercialised by AstraZeneca and Daiichi Sankyo.

The approval by the Food and Drug Administration (FDA) was based on positive results from the DESTINY-Breast03 Phase III trial that showed Enhertu reduced the risk of disease progression or death by 72% versus trastuzumab emtansine (T-DM1) (hazard ratio [HR] 0.28; 95% confidence interval [CI]: 0.22-0.37; p<0.0001) in patients with HER2-positive unresectable and/or metastatic breast cancer previously treated with trastuzumab and a taxane.

The approval was granted under the FDA’s Real-Time Oncology Review (RTOR) programme and converts the accelerated approval of Enhertu in later line HER2-positive metastatic breast cancer to standard approval, broadening Enhertu’s breast cancer indication in the US to earlier lines of use in patients with HER2-positive metastatic breast cancer.

Erika Hamilton, MD, Director of the Breast Cancer and Gynecological Cancer Research Program for Sarah Cannon Research Institute, Nashville, Tennessee, US, said: "Enhertu has demonstrated significant progression-free survival in the earlier metastatic setting, potentially establishing it as a new standard of care in previously treated patients with HER2-positive metastatic breast cancer. Today’s approval is an important milestone for the clinical community as we will now be able to offer Enhertu to these patients earlier in their treatment."

Catherine Ormerod, Executive Vice President, Strategy and Mission, Living Beyond Breast Cancer, said: "This is an important day for the breast cancer community. With this approval, Enhertu now provides a new treatment option for patients with HER2-positive metastatic breast cancer which can be used earlier in treatment to potentially delay progression of disease."

Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, said: "Enhertu is already established in the later-line treatment of patients with HER2-positive metastatic breast cancer, and we are thrilled that with this approval, patients in the US will now be able to access the transformative potential of Enhertu earlier in their treatment. We look forward to bringing this important, potentially paradigm-shifting medicine to even more patients across the globe in an earlier setting as quickly as possible."

Ken Keller, Global Head, Oncology Business and President and CEO, Daiichi Sankyo, Inc, said: "Today’s FDA approval, which converts the accelerated approval of Enhertu to regular approval, highlights the importance of the FDA’s accelerated pathway that allows for earlier approval of medicines to treat serious medical conditions such as breast cancer. Data from DESTINY-Breast03 not only confirmed the results of DESTINY-Breast01, but also demonstrated the superiority of Enhertu in prolonging progression-free survival compared to T-DM1 in an earlier setting of HER2-positive metastatic breast cancer."

The DESTINY-Breast03 Phase III trial results were recently published online in The New England Journal of Medicine.1 In the trial, the safety profile of Enhertu was consistent with previous clinical trials, with no new safety concerns identified and no Grade 4 or 5 treatment-related interstitial lung disease events.

Based on the DESTINY-Breast03 data, fam-trastuzumab deruxtecan-nxki (Enhertu) recently was added to the NCCN Clinical Practical Guidelines in Oncology (NCCN Guidelines) as the Category 1 preferred regimen as second-line therapy for recurrent unresectable (local or regional) or Stage IV HER2-positive disease.2

The US regulatory submission was reviewed under Project Orbis, which provides a framework for concurrent submission and review of oncology medicines among participating international partners. Five national health authorities collaborated with the FDA on this review, including the Australian Therapeutic Goods Administration, the Brazilian Health Regulatory Agency (ANVISA), Health Canada, Israel’s Ministry of Health Pharmaceutical Administration and Switzerland’s Swissmedic.

This approval follows the recent Priority Review and Breakthrough Therapy Designation of Enhertu in the US in this earlier setting.

Regulatory applications for Enhertu are currently under review in Europe, Japan and several other countries for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received a prior anti-HER2-based regimen based on the results from the DESTINY-Breast03 trial.

Notes

Financial considerations
Following this approval for Enhertu in the US, an amount of $100m is due from AstraZeneca to Daiichi Sankyo as a 2nd-line milestone payment in HER2-positive metastatic breast cancer. In AstraZeneca, the milestones paid will be capitalised as an addition to the upfront payment made in 2019 and subsequent capitalised milestones and amortised through the profit and loss.

Sales of Enhertu in the US are recognised by Daiichi Sankyo. AstraZeneca reports its share of gross profit margin from Enhertu sales in the US as collaboration revenue in the Company’s financial statements. For further details on the financial arrangements, please consult the collaboration agreement from March 2019.

HER2-positive breast cancer
Breast cancer is the most common cancer and is one of the leading causes of cancer-related deaths worldwide and in the US.3,4 More than two million patients with breast cancer were diagnosed in 2020, with nearly 685,000 deaths globally.3 More than 290,000 new cases are expected in the US in 2022, with more than 43,000 deaths.5 Approximately one in five cases of breast cancer are considered HER2-positive.6

HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumours including breast, gastric, lung and colorectal cancers.7 HER2 protein overexpression may occur as a result of HER2 gene amplification and is often associated with aggressive disease and poor prognosis in breast cancer.8

Despite initial treatment with trastuzumab and a taxane, patients with HER2-positive metastatic breast cancer will often experience disease progression.9 More treatment options are needed to further delay progression and extend survival.9-11

DESTINY-Breast03
DESTINY-Breast03 is a global, head-to-head, randomised, open-label, registrational Phase III trial evaluating the efficacy and safety of Enhertu (5.4mg/kg) versus T-DM1 in patients with HER2-positive unresectable and/or metastatic breast cancer previously treated with trastuzumab and a taxane.

The primary efficacy endpoint of DESTINY-Breast03 is progression-free survival (PFS) based on blinded independent central review. Secondary efficacy endpoints include overall survival, objective response rate (ORR), duration of response, PFS based on investigator assessment and safety.

DESTINY-Breast03 enrolled approximately 500 patients at multiple sites in Asia, Europe, North America, Oceania and South America. For more information about the trial, visit ClinicalTrials.gov.

Enhertu
Enhertu is a HER2-directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, Enhertu is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced programme in AstraZeneca’s ADC scientific platform. Enhertu consists of a HER2 monoclonal antibody attached to a topoisomerase I inhibitor payload, an exatecan derivative, via a stable tetrapeptide-based cleavable linker.

Enhertu (5.4mg/kg) is approved in the US for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received a prior anti-HER2-based regimen either in the metastatic setting, or in the neoadjuvant or adjuvant setting and have developed disease recurrence during or within six months of completing therapy, based on results from the DESTINY-Breast03 trial.

Enhertu (5.4mg/kg) is also approved in approximately 40 countries for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens based on the results from the DESTINY-Breast01 trial.

Enhertu (6.4mg/kg) is approved in several countries for the treatment of adult patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01 trial.

Enhertu development programme
A comprehensive development programme is underway globally, evaluating the efficacy and safety of Enhertu monotherapy across multiple HER2-targetable cancers, including breast, gastric, lung and colorectal cancers. Trials in combination with other anticancer treatments, such as immunotherapy, are also underway.

Regulatory applications for Enhertu are currently under review in Europe, Japan and several other countries for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received a prior anti-HER2 based regimen based on the results from the DESTINY-Breast03 trial.

Enhertu was granted Breakthrough Therapy Designation in the US for the treatment of adult patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-negative) breast cancer who have received a prior systemic therapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy, based on the results of the DESTINY-Breast04 trial. Patients with hormone receptor (HR) positive breast cancer should additionally have received or be ineligible for endocrine therapy.

Enhertu is also currently under review in the US for the treatment of adult patients with unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumours have a HER2 (ERBB2) mutation and who have received a prior systemic therapy, based on the DESTINY-Lung01 trial, and in Europe for the treatment of adult patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma who have received a prior anti-HER2-based regimen based on the DESTINY-Gastric01 and DESTINY-Gastric02 trials.

Daiichi Sankyo collaboration
Daiichi Sankyo Company, Limited (TSE:4568) [referred to as Daiichi Sankyo] and AstraZeneca entered into a global collaboration to jointly develop and commercialise Enhertu (a HER2-directed ADC) in March 2019, and datopotamab deruxtecan (DS-1062; a TROP2-directed ADC) in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights. Daiichi Sankyo is responsible for manufacturing and supply of Enhertu and datopotamab deruxtecan.

AstraZeneca in breast cancer
Driven by a growing understanding of breast cancer biology, AstraZeneca is starting to challenge, and redefine, the current clinical paradigm for how breast cancer is classified and treated to deliver even more effective treatments to patients in need – with the bold ambition to one day eliminate breast cancer as a cause of death.

AstraZeneca has a comprehensive portfolio of approved and promising compounds in development that leverage different mechanisms of action to address the biologically diverse breast cancer tumour environment. AstraZeneca aims to continue to transform outcomes for HR-positive breast cancer with foundational medicines Faslodex (fulvestrant) and Zoladex (goserelin) and the next-generation oral selective oestrogen receptor degrader (SERD) and potential new medicine camizestrant.

PARP inhibitor Lynparza (olaparib) is a targeted treatment option that has been studied in HER2-negative early and metastatic breast cancer patients with an inherited BRCA mutation. AstraZeneca with MSD (Merck & Co., Inc. in the US and Canada) continue to research Lynparza in metastatic breast cancer patients with an inherited BRCA mutation and are exploring new opportunities to treat these patients earlier in their disease.

Building on the first approval of Enhertu, a HER2-directed ADC, in previously treated HER2-positive metastatic breast cancer, AstraZeneca and Daiichi Sankyo are exploring its potential in earlier lines of treatment and in new breast cancer settings.

To bring much needed treatment options to patients with triple-negative breast cancer, an aggressive form of breast cancer, AstraZeneca is testing immunotherapy Imfinzi (durvalumab) in combination with other oncology medicines, including Lynparza and Enhertu, evaluating the potential of AKT kinase inhibitor, capivasertib, in combination with chemotherapy, and collaborating with Daiichi Sankyo to explore the potential of TROP2-directed ADC, datopotamab deruxtecan.

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 5, 2022 argenx SE (Euronext & Nasdaq: ARGX), a global immunology company committed to improving the lives of people suffering from severe autoimmune diseases, reported financial results for the first quarter 2022 and provided a business update (Press release, argenx, MAY 5, 2022, View Source [SID1234613607]).

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In a separate press release issued today, argenx also announced positive results from the Phase 3 ADVANCE trial evaluating VYVGART for the treatment of adult patients with ITP. The primary endpoint, demonstrating a significantly higher proportion of VYVGART-treated patients achieved a sustained platelet response than patients receiving placebo, and additional key secondary endpoints were met.

"Our VYVGART commercial launch is off to a strong start, underscoring the significant unmet need for a new treatment option in gMG. We are very encouraged by the early demand from patients and physicians and our team continues to meet the challenge with outstanding execution and deep engagement with our key stakeholders. We look forward to our imminent commercial launch in Japan and an upcoming regulatory decision in Europe, which support our goal to make VYVGART available worldwide. We are confident that the relationships we are building today with the gMG community will establish a strong foundation to continue to deliver on behalf of patients," commented Tim Van Hauwermeiren, Chief Executive Officer of argenx.

"The positive readout from our first registrational ITP trial highlights the promise of efgartigimod as a pipeline-in-a-product with the potential to reach a variety of IgG-mediated autoimmune diseases, even beyond the ten indications we are currently evaluating. We are on track to achieve our argenx 2025 goal to build the next great immunology company while bringing breakthrough innovations to patients and creating long-term value for our stakeholders."

FIRST QUARTER 2022 AND RECENT BUSINESS UPDATE

VYVGART Launch Progress

VYVGART is the first-approved neonatal Fc receptor (FcRn) blocker in the U.S. and Japan. VYVGART is approved in the U.S. for the treatment of adult generalized myasthenia gravis (gMG) patients who are anti-acetylcholine receptor (AChR) antibody positive and in Japan for adult gMG patients. The global launch strategy is on track to make VYVGART available in Europe, China and Canada, as well as select additional regions.

Generated net product revenues of $21.2 million for first full quarter of VYVGART commercial launch in U.S.
Japan commercial launch to start this month following addition of VYVGART to National Health Insurance (NHI) drug price list on April 20, 2022
Decision from European Medicines Agency on Marketing Authorization Application expected in second half of 2022
Zai Lab to file for approval in China in mid-2022 and Medison in Israel in second quarter of 2022
Efgartigimod Research and Development

argenx is positioned to expand its leadership position in FcRn blockade to include ten total autoimmune indications by the end of 2022. Six registrational trials are ongoing with four new proof-of-concept trials to start this year across multiple therapeutic franchises.

Neuromuscular franchise
Biologics License Application (BLA) on track to be filed by end of year for subcutaneous (SC) efgartigimod for gMG, following positive topline results from Phase 3 ADAPT-SC trial
Topline data from registrational ADHERE trial of SC efgartigimod for chronic inflammatory demyelinating polyneuropathy (CIDP) expected in first quarter of 2023
Registrational ALKIVIA trial on track to start this quarter for three subtypes of idiopathic inflammatory myopathies (myositis), including immune-mediated necrotizing myopathy, anti-synthetase syndrome and dermatomyositis; interim analysis planned of first 30 patients of each subtype
Hematology franchise
Positive topline data of VYVGART for primary ITP reported today
Primary endpoint was met; significantly higher proportion of patients receiving VYVGART achieved a sustained platelet response than patients receiving placebo
Statistically significant separation from placebo in key platelet-derived secondary endpoints
Safety and tolerability profile confirmed in second indication
Topline data from second registrational ADVANCE-SC trial of SC efgartigimod for primary ITP expected in first quarter of 2023
Dermatology franchise
Enrollment expanded in registrational ADDRESS trial of SC efgartigimod for pemphigus vulgaris and foliaceus in order to manage ongoing impact of war in Ukraine; topline data now expected in second half of 2023
Registrational BALLAD trial ongoing of SC efgartigimod for bullous pemphigoid with interim analysis planned of first 40 patients
Proof-of-concept trials to be launched in collaboration with Zai Lab and IQVIA
Zai Lab to launch Phase 2 trials in lupus nephritis and membranous nephropathy in 2022 with argenx to lead global registrational programs for each potential indication
IQVIA to launch Phase 2 trials in primary Sjogren’s syndrome in second half of 2022 and COVID-19-mediated postural orthostatic tachycardia syndrome (POTS) in mid-2022
Pipeline Progress

argenx is developing ARGX-117 and ARGX-119, which both have pipeline-in-a-product potential for multiple autoimmune indications.

ARGX-117 (C2 inhibitor)
Proof-of-concept ARDA trial ongoing to evaluate safety, tolerability, and potential dosing regimen in multifocal motor neuropathy (MMN)
Phase 2 proof-of-concept trial expected to start in 2022 for prevention of delayed graft function and/or allograft failure after kidney transplantation
ARGX-119 (muscle-specific kinase (MuSK) agonist)
Phase 1 dose-escalation trial in healthy volunteers expected to start after Clinical Trial Application filing in fourth quarter of 2022
A subsequent Phase 1b trial will assess early signal detection in patients with congenital myasthenic syndrome and MuSK-associated myasthenia gravis
Upcoming Medical Meeting Presentations

14th Myasthenia Gravis Foundation of America International Conference on Myasthenia and Related Disorders (May 10-12, Miami, FL)
Society for Investigative Dermatology Annual Meeting (May 18-21, Portland, Oregon)
Annual Meeting of the Japanese Society of Neurology (May 18-22, Tokyo, Japan)
8th Congress of the European Academy of Neurology (June 25-28, Vienna, Austria)
17th International Congress on Neuromuscular Diseases (July 5-9, Brussels, Belgium)
DETAILS OF THE FINANCIAL RESULTS

Total operating income for the three months ended March 31, 2022 was $31.5 million, compared to $178.6 million for the three months ended March 31, 2021, and consists of:

Product net sales from sales of VYVGART in the U.S. for the three months ended March 31, 2022 were $21.2 million, following the approval of VYVGART by the U.S. Food and Drug Administration (FDA) on December 17, 2021. No product sales were recognized during the comparable prior period.
Collaboration revenue for the three months ended March 31, 2022 was $2.2 million, compared to $158.2 million for three months ended March 31, 2021, resulting in a decrease of $155.9 million. The collaboration revenue for the three months ended March 31, 2021 was primarily attributable to the closing of the strategic collaboration for efgartigimod with Zai Lab, resulting in the recognition of $151.9 million in collaboration revenue.
Other operating income for the three months ended March 31, 2022 was $8.1 million, compared to $20.4 million for three months ended March 31, 2021, resulting in a decrease of $12.3 million. During the three months ended March 31, 2021, the fair value of the argenx profit share in AgomAb Therapeutics NV increased by $11.2 million. There was no change in the fair value during the three months ended March 31, 2022.
Total operating expenses for the three months ended March 31, 2022 were $254.2 million, compared to $178.6 million for the three months ended March 31, 2021, and consists of:

Cost of sales for the three months ended March 31, 2022 amounted to $1.4 million. The cost of sales was recognized with respect to the sale of VYVGART in the U.S. during the first quarter of 2022. There was no cost of sales recognized in the comparable prior period.
Research and development expenses increased by $29.6 million for the three months ended March 31, 2022 to $152.0 million, compared to $122.3 million for the three months ended March 31, 2021. The increase resulted primarily from higher external research and development expenses, mainly related to the efgartigimod program in various indications and other clinical and preclinical programs.
Selling, general and administrative expenses totaled $100.9 million for the three months ended March 31, 2022, compared to $56.3 million for the three months ended March 31, 2021. The increase resulted primarily from higher professional and marketing fees linked to the commercialization of VYVGART in the U.S. and Japan and higher personnel expenses increased due to a planned increase in headcount.
Exchange losses totaled $7.2 million for the three months ended March 31, 2022, compared to $28.9 million for the three months ended March 31, 2021 and are mainly attributable to unrealized exchange rate losses on cash, cash equivalents and current financial assets position in Euro.

Income tax totaled $2.9 million of tax income for the three months ended March 31, 2022, compared to $11.2 million of tax expense for the comparable prior period. Tax income for the three months ended March 31, 2022 consists of $5.0 million of income tax expense and $7.9 million of deferred tax income, compared to $6.2 million of income tax expense and $5 million of deferred tax expense for the comparable prior period.

Net loss for the three months ended March 31, 2022 was $227.2 million compared to $40.4 million for the comparable prior year period. On a per weighted average share basis, the net loss was $4.36 and $0.81 for the three months ended March 31, 2022 and 2021, respectively.

Cash, cash equivalents and current financial assets totaled $2,855.4 million as of March 31, 2022, compared to $2,336.7 million as of December 31, 2021. The increase in cash and cash equivalents and current financial assets resulted primarily from the closing of a global offering of shares, including a U.S. offering and a European private placement, which resulted in the receipt of $761.0 million in net proceeds in March 2022, partially offset by the net cash flows used in operating activities, primarily towards the commercial launch of VYVGART in the U.S. and Japan and continued investment in pipeline expansion.

FINANCIAL GUIDANCE

As of March 31, 2022, argenx had $2.9 billion in cash, cash equivalents and current financial assets. Based on current plans to fund anticipated operating expenses and capital expenditures, argenx expects to utilize approximately $1 billion of its available cash in 2022. The increased spend will support the global VYVGART launches, clinical development of efgartigimod in 10 indications and ARGX-117 in two indications, investment in the global supply chain, and continued focus on pipeline expansion through the Immunology Innovation Program.

EXPECTED 2022 FINANCIAL CALENDAR

July 28, 2022: HY 2022 financial results and business update
October 27, 2022: Q3 2022 financial results and business update
CONFERENCE CALL DETAILS

The first quarter 2022 business update will be discussed during a conference call and webcast presentation today at 2:30 pm CEST/8:30 am ET. A webcast of the live call may be accessed on the Investors section of the argenx website at argenx.com/investors. A replay of the webcast will be available on the argenx website.