On August 4, 2023 Galapagos NV (Euronext & NASDAQ: GLPG) reported its first half-year 2023 financial results, a year-to-date business update and its outlook for the remainder of 2023 (Press release, Galapagos, AUG 4, 2023, View Source [SID1234633822]). The results are further detailed in the H1 2023 financial report available on the financial reports section of the corporate website.

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"The market and competitive landscape for the JAK class in Europe has changed significantly over the past six months, negatively impacting net sales of Jyseleca and leading us to revise our 2023 net sales guidance for Jyseleca in rheumatoid arthritis and ulcerative colitis from €140-€160 million to €100-€120 million. In response to that, we are in the process of evaluating various strategic options for Jyseleca. We have a strong cash position of €3.9 billion and we will continue to deploy our resources in our strategic areas of immunology and oncology, including externally sourced innovative product candidates, to further build and expand our portfolio. Despite lower than anticipated net sales for Jyseleca, we reiterate our cash burn guidance of €380-€420 million," said Thad Huston, CFO and COO of Galapagos.

Dr. Paul Stoffels1, CEO and Chairman of Galapagos added: "Our commitment to providing transformational medicines to patients worldwide remains our core focus. We have successfully implemented our R&D strategy focused on best-in-class medicines to accelerate innovation, aiming to generate short and long-term value for all our stakeholders. We are actively building a differentiated discovery pipeline of best-in-class small molecules, CAR-T cell therapies and biologicals in our core areas of immunology and oncology. In addition, our ongoing clinical programs across our therapeutic areas are progressing well, and we are optimistic about the global potential of our point-of-care CAR-T cell therapy portfolio in hematological malignancies. Furthermore, in immunology, we have continued to expand our clinical pipeline of small molecules, while leveraging our CAR-T capabilities to start clinical development in refractory systemic lupus erythematosus with a CD19 CAR-T candidate."

Half-Year 2023 operational performance

Immunology portfolio

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Jyseleca (filgotinib) (JAK1)

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Jyseleca is reimbursed for rheumatoid arthritis (RA) and ulcerative colitis (UC) in 19 and 18 countries respectively. Sobi2, our distribution and commercialization partner in Eastern and

1
Throughout this press release, ‘Dr. Paul Stoffels’ should be read as ‘Dr. Paul Stoffels, acting via Stoffels IMC BV’

2
Swedish Orphan Biovitrum AB

LOGO

Central Europe, Portugal, Greece, and the Baltic countries, launched Jyseleca in Czech Republic and Poland in UC and in Croatia in RA. The commercial launch of Jyseleca in Poland resulted in a €1 million milestone in the first half of 2023.

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The European Commission endorsed the recommendation of the Pharmaceutical Risk Assessment Committee (PRAC) to add measures to minimize risks of serious side effects with the JAK inhibitor class of medicines used for chronic inflammatory disorders. The product information for all JAK inhibitors has been updated accordingly to include these recommendations and warnings.

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We dosed the first patients in the pivotal Phase 3 OLINGUITO study in axial spondyloarthritis (AxSpA).

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Based on the topline results from the Phase 3 DIVERSITY study in Crohn’s disease (CD), we decided not to submit a Marketing Authorization Application (MAA) in Europe in this indication and not to proceed with the MAA for filgotinib in UC in Switzerland.

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We presented various data abstracts at the annual ECCO and EULAR congresses in Europe.

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Our pipeline assets

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First patients dosed in the Phase 2 GALARISSO study with oral, selective tyrosine kinase 2 (TYK2) inhibitor, GLPG3667, in dermatomyositis (DM).

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Clinical trial application (CTA) filed to start clinical development of a CD19 CAR-T candidate in patients with refractory systemic lupus erythematosus (rSLE).

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Multiple small molecules programs initiated to further build our research pipeline.

Oncology portfolio

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We are encouraged by the initial safety, efficacy and point-of-care feasibility results we have observed in the Phase 1/2 studies with our CD19 CAR-T candidates, GLPG5101 and GLPG5201, which underscore the potential global transformational impact our differentiated approach to CAR-T cell therapy could have on patients.

GLPG5101 in relapsed/refractory non-Hodgkin’s lymphoma (rrNHL)

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We are in the final stages of the Phase 1 part of the ongoing Phase 1/2 ATALANTA-1 study, which enrolled patients with diffuse large B cell lymphoma, mantle cell lymphoma and indolent lymphoma. To generate a robust data package that is informative for further development, we have decided to include more patients of certain subpopulations in the Phase 1 dose-escalation cohort of ATALANTA-1.

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The first patients with indolent lymphoma and mantle cell lymphoma in the Phase 2 dose- expansion part of ATALANTA-1 have been dosed.

GLPG5201 in relapsed/refractory chronic lymphocytic leukemia (rrCLL), with or without Richter’s transformation (RT)

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We presented promising interim safety, efficacy and point-of-care manufacturing data from 7 eligible patients3 of the ongoing Phase 1/2 EUPLAGIA-1 study at two major scientific meetings in Europe: objective response rate of 100%; no cytokine release syndrome higher than grade 2, or immune effector cell-associated neurotoxicity syndrome observed.4

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We are recruiting the last patients in the Phase 1 dose-escalation part of EUPLAGIA-1 and preparations to start the Phase 2 dose-expansion cohort of the study are ongoing.

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We initiated multiple programs spanning various drug modalities, including biologicals, CAR-T cell therapies and small molecules, to further build our research pipeline.

Corporate update

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At the Annual General Meeting held on 25 April 2023, all proposed resolutions were approved.

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The Board of Directors created 1,975,000 subscriptions rights under new subscription right plans.

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Thad Huston was appointed as Chief Financial Officer (CFO) and Chief Operating Officer (COO), succeeding Bart Filius, per 1 July 2023.

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The Board of Directors appointed Dr. Susanne Schaffert as non-executive independent Director by way of co-optation on 12 June 2023, replacing Dr. Rajesh Parekh who stepped down on 10 June 2023.

3
Cut-off date for efficacy and safety analysis: 9 January 2023

4
4 As published in the press release of February 9, 2023: Galapagos presented encouraging initial safety and efficacy data at 2023 EBMT-EHA for point-of-care manufactured CAR-T candidate, GLPG5201, in rrCLL

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We completed the integrated drug discovery collaboration transaction with NovAliX on 30 June 2023, effective as from 1 July 2023. Under the terms of the agreement, Galapagos’ drug discovery and research activities conducted in Romainville, France, and Galapagos’ employees in Romainville, which are exclusively dedicated to the operation of these activities, are transferred to NovAliX who will assume all ongoing research and discovery activities in Romainville. In return, Galapagos is committed to utilizing the research capabilities and expertise of NovAliX through a five year-collaboration and within the context of the company’s R&D portfolio.

First half-year 2023 financial highlights (unaudited)

(€ millions, except basic & diluted income/loss (-) per share)

Six months ended
30 June Change
2023 2022
Product net sales

54.3 35.4 +54 %
Collaboration revenues

274.5 238.6 +15 %

Total net revenues

328.8 274.0 +20 %

Cost of sales

(7.8 ) (5.5 ) +41 %
R&D expenditure

(211.9 ) (249.5 ) -15 %
G&Aii and S&Miii expenses

(121.6 ) (134.0 ) -9 %
Other operating income

23.8 17.6 +35 %


Operating profit/loss (-)

11.3 (97.5 )


Fair value adjustments and net currency exchange differences

0.2 71.9
Net other financial result

30.4 (4.3 )
Income taxes

(13.6 ) (2.5 )

Net profit/loss (-) of the period

28.3 (32.3 )

Basic and diluted income/loss (-) per share (€)

0.43 (0.49 )

Current financial investments and cash and cash equivalents

3,874.9 4,429.0

Details of the first half-year 2023 financial results

Total net revenues for the six months ended 30 June 2023 was €328.8 million, compared to €274.0 million for the six months ended 30 June 2022, and consisted of:

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Product net sales of Jyseleca in Europe for the first six months of 2023 amounting to €54.3 million (€35.4 million in the first half-year of 2022).

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Collaboration revenues of €274.5 million for the first six months of 2023, compared to €238.6 million for the first six months of 2022.

Collaboration revenues increased mainly due to revenue recognition related to the collaboration agreement with Gilead for the filgotinib development amounting to €154.9 million in the first six months of 2023 compared to €115.3 million for the same period last year. This increase is primarily driven by a positive catch up of revenue explained by a decrease in the total estimated remaining costs to complete the filgotinib development. This was a consequence of the topline results from Phase 3 DIVERSITY trial of filgotinib in CD and our decision not to submit a Marketing Authorization Application in Europe.

Our deferred income balance on 30 June 2023 includes €1.4 billion allocated to our drug discovery platform that is recognized linearly over the remaining period of our 10-year collaboration, and €0.3 billion allocated to the filgotinib development that is recognized over time until the end of the development period.

Total operating profit for the six months ended 30 June 2023 was €11.3 million, compared to total operating loss of €97.5 million for the first six months ended 30 June 2022.

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Cost of sales related to Jyseleca net sales in the first six months of 2023 amounted to €7.8 million (€5.5 million in the first half-year of 2022).

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R&D expenditure in the first six months of 2023 amounted to €211.9 million, compared to €249.5 million for the first six months of 2022. This decrease was primarily explained by an impairment recorded in the first six months of 2022 of €26.7 million of previously capitalized upfront fees related to our collaboration with Molecure on the dual chitinase inhibitor OATD-01 (GLPG4716), as well as by decreased personnel and subcontracting costs.

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S&M and G&A expenses amounted to €121.6 million in the first six months of 2023, compared to €134.0 million in the first six months of 2022. This decrease was primarily due to a decrease in personnel costs and agency deliverables.

•
Other operating income amounted to €23.8 million in the first six months of 2023, compared to €17.6 million for the same period last year.

Net financial income in the first six months of 2023 amounted to €30.6 million, compared to net financial income of €67.7 million for the first six months of 2022.

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Fair value adjustments and net currency exchange differences in the first six months of 2023 amounted to €0.2 million, compared to fair value adjustments and net currency exchange gains of €71.9 million for the first six months of 2022, and were primarily attributable to €11.4 million of unrealized currency exchange losses on our cash and cash equivalents and current financial investments at amortized cost in U.S. dollars, offset by €12.7 million of positive changes in (fair) value of current financial investments.

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Net other financial income in the first six months of 2023 amounted to €30.4 million, compared to net other financial expenses of €4.3 million for the first six months of 2022, and was primarily attributable to €33.4 million of interest income, which increased significantly due to the increase in interest rates.

We reported a group net profit for the first six months of 2023 of €28.3 million, compared to a group net loss of €32.3 million for the first six months of 2022.

Cash position

Current financial investments and cash and cash equivalents totaled €3,874.9 million on 30 June 2023, as compared to €4,094.1 million on 31 December 2022.

Total net decrease in cash and cash equivalents and current financial investments amounted to €219.1 million during the first six months of 2023, compared to a net decrease of €274.2 million during the first six months of 2022. This net decrease was composed of (i) €224.3 million of operational cash burn, (ii) €9.3 million of mainly negative exchange rate differences, offset by (iii) €1.8 million of cash proceeds from capital and share premium increase from exercise of subscription rights in the first six months of 2023, and (iv) €12.7 million positive changes in (fair) value of current financial investments.

Outlook 2023

Financial outlook

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In response to the changing market dynamics and the competitive landscape for the JAK class in Europe, we are in the process of evaluating various strategic options for Jyseleca and have lowered our net 2023 sales guidance for Jyseleca in RA and UC to €100-€120 million, compared to €140-160 million initially guided in our full year 2022 results in February.

•
Despite the lower than anticipated net sales for Jyseleca, we reiterate our full year 2023 cash burn guidance in the range of €380-€420 million. We will continue to focus on expanding our portfolio and will deploy our resources in our strategic core areas of immunology and oncology.

R&D outlook

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Immunology portfolio

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We expect to announce Phase 4 results from the FILOSOPHY real-world evidence study of filgotinib in patients with RA at a future scientific conference (subject to abstract acceptance) and to initiate the Phase 2 pediatric study in patients with juvenile arthritis later this year.

•
We aim to start dosing patients with SLE in the Phase 2 GALACELA study of oral, selective TYK2 inhibitor, GLPG3667.

•
Following the potential approval of the CTA submitted in Europe for CD19 CAR-T candidate, GLPG5101, in patients with rSLE, we expect to open the clinical centers in the coming months.

•
Oncology portfolio

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As we continue to build a solid data package, we aim to release an update on the ATALANTA-1 and EUPLAGIA-1 Phase 1 studies with GLPG5101 and GLPG5201 in rrNHL and rrCLL respectively later this year. We intend to present detailed data at a forthcoming hematology scientific conference (subject to abstract acceptance) before year-end.

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The Phase 1 part of EUPLAGIA-1 study with GLPG5201 is close to completion and we aim to initiate the Phase 2 dose-expansion cohort in the first half of 2024.

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In the first half of 2024, we anticipate submitting an investigational new drug application (IND) in the US to start clinical development with our CD19 CAR-T program.

•
We expect to start the Phase 1/2 PAPILIO-1 study with BCMA CAR-T candidate, GLPG5301, in relapsed/refractory multiple myeloma (rrMM) after summer5.

Business development

•
We continue to explore additional business development opportunities to further leverage our internal capabilities and expand our portfolio in our core areas of growth and value creation.

First half-year 2023 financial report

Galapagos’ financial report for the first six months ended 30 June 2023, including details of the unaudited consolidated results, is accessible on the financial reports section of our website.

Conference call and webcast presentation

We will host a conference call and webcast presentation tomorrow 4 August 2023, at 14:00 CET / 8:00 am ET. To participate in the conference call, please register in advance using this link, after which the dial-in numbers will be provided. The conference call can be accessed 10 minutes prior to the start by using the conference access information provided in the email after registration, or by selecting the "call me" feature.

The live webcast is available on glpg.com or via the following link. The archived webcast will be available for replay shortly after the close of the call on the investor section of the website.

Financial calendar 2023
2 November 2023 Third quarter 2023 results (webcast 3 November 2023)
22 February 2024 Full year 2023 results (webcast 23 February 2024)

On August 4, 2023 Foghorn Therapeutics Inc. (Nasdaq: FHTX), a clinical-stage biotechnology company pioneering a new class of medicines that treat serious diseases by correcting abnormal gene expression, reported a financial and corporate update in conjunction with the Company’s 10-Q filing for the quarter ended June 30, 2023 (Press release, Foghorn Therapeutics, AUG 4, 2023, View Source [SID1234633821]). With an initial focus in oncology, Foghorn’s Gene Traffic Control Platform and resulting broad pipeline have the potential to transform the lives of people suffering from a wide spectrum of diseases.

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"Foghorn made important progress across both our clinical and preclinical pipeline in the second quarter. We successfully resolved the clinical hold for FHD-286 in AML and disclosed the clinical data from the Phase 1 study which suggested that FHD-286 is a potent, broad-based differentiation agent. We are on track to initiate dosing in a combination study of FHD-286 in AML in the third quarter. We continue to advance our selective BRM, selective CBP, selective EP300, and selective ARID1B programs, demonstrating our ability to repeatedly drug important targets in oncology," said Adrian Gottschalk, President and Chief Executive Officer of Foghorn.

Key Recent Updates and Upcoming Milestones

•FHD-286. FHD-286 is a potent, selective inhibitor of the BRG1 and BRM subunits of the BAF chromatin remodeling complex where dependency on BRG1/BRM is well-established preclinically with multiple tumor types, including acute myelogenous leukemia (AML)/myelodysplastic syndrome (MDS), non–small cell lung cancer (NSCLC) and prostate cancer.
◦AML/MDS Update. Foghorn plans to commence a Phase 1 study of FHD-286 in combination with decitabine or low-dose cytarabine (LDAC) in relapsed and/or refractory AML patients. The decision to advance to the Phase 1 combination study is based on clinical data demonstrating FHD-286’s effect as a broad-based differentiation agent, its safety profile, as well as supportive preclinical combination data, including robust efficacy data in multiple CDX and PDX models.
◦mUM Update. On June 28, 2023, Foghorn announced data from the Phase 1 dose escalation safety study of FHD-286 in metastatic uveal melanoma (mUM). These data reinforced the safety and tolerability profile of FHD-286. At this time, the company does not plan to advance FHD-286 in uveal melanoma independently.

•Differentiated Pipeline Advancement. Foghorn continues to expand its platform and pipeline. The Company anticipates the potential for six new investigational new drug (IND) applications in the next four years. The Company continues to progress programs for multiple targets which include chromatin remodeling complexes, transcription factors, helicases and other chromatin related factors. These targets include Selective BRM* and wholly owned programs including CBP, EP300, and ARID1B, as well as other undisclosed targets, which combined could address more than 20 tumor types impacting more than 500,000 new patients annually.

•Strategic Collaborations. Foghorn continued to progress its strategic collaborations with world-leading pharmaceutical companies, which validate the rigor of our science, highlight the importance of the targets we are tackling, and confirm the relevance of the biology on which Foghorn is focused.
◦In December 2021, Foghorn entered into a strategic collaboration with Loxo@Lilly. In 2023, Foghorn anticipates continued progress across the collaboration including a co-development and co-commercialization agreement on the Selective BRM program*, an additional undisclosed oncology target and three additional discovery programs. The Selective BRM program is on track to transition to Loxo@Lilly in the second half of 2023.
◦In July 2020, Foghorn entered into a strategic collaboration with Merck Sharp & Dohme. Through the first two quarters of 2023, Foghorn continued to utilize its Gene Traffic Control platform to discover and develop novel therapeutics under the collaboration based on disruptors of a specified transcription factor target.

*In December 2021, Foghorn announced a strategic collaboration with Loxo@Lilly to create novel oncology medicines. The collaboration includes a co-development and co-commercialization agreement for Foghorn’s Selective BRM oncology program and an additional undisclosed oncology target. In addition, the collaboration includes three discovery programs using Foghorn’s proprietary Gene Traffic Control platform.

Second Quarter 2023 Financial Highlights

•Strong Balance Sheet and Cash Runway. As of June 30, 2023, the Company had $284.3 million in cash, cash equivalents and marketable securities, which provides a cash runway into the second half of 2025.

•Collaboration Revenues. Collaboration revenue was $5.6 million for the three months ended June 30, 2023, compared to $4.5 million for the three months ended June 30, 2022. The increase year-over-year was primarily driven by revenue recognized under the Lilly collaboration agreement.

•Research and Development Expenses. Research and development expenses were $29.2 million for the three months ended June 30, 2023, compared to $26.0 million for the three months ended June 30, 2022. This increase was primarily due to costs associated with continued investment in R&D personnel and platform and early-stage research investments, modestly offset by a decline in clinical trial spend.

•General and Administrative Expenses. General and administrative expenses were $8.4 million for the three months ended June 30, 2023, compared to $7.7 million for the three months ended June 30, 2022. This increase was primarily due to an increase in investments to support the growing business which included increases in personnel-related costs and stock-based compensation expense.

•Net Loss. Net loss was $29.5 million for the three months ended June 30, 2023, compared to a net loss of $27.3 million for the three months ended June 30, 2022.

About FHD-286
FHD-286 is a highly potent, selective, allosteric and orally available, small-molecule, enzymatic inhibitor of BRG1 (SMARCA4) and BRM (SMARCA2), two highly similar proteins that are the ATPases, or the catalytic engines of the BAF complex, one of the key regulators within the chromatin regulatory system. In preclinical studies, FHD-286 has shown anti-tumor activity across a broad range of malignancies including both hematologic and solid tumors. FHD-286 is being developed for relapsed and/or refractory AML, and the company plans to commence a Phase 1 study, in combination with decitabine or cytarabine, in the third quarter of 2023.

About AML
Adult acute myeloid leukemia (AML) is a cancer of the blood and bone marrow and the most common type of acute leukemia in adults. AML is a diverse disease associated with multiple genetic mutations. It is diagnosed in about 20,000 people every year in the United States.

On August 4, 2023 Eli Lilly and Company (NYSE: LLY) reported topline results from the LIBRETTO-431 study evaluating Retevmo versus platinum-based chemotherapy plus pemetrexed – with or without pembrolizumab – as an initial treatment for patients with rearranged during transfection (RET) fusion-positive advanced or metastatic non-small cell lung cancer (NSCLC) (Press release, Eli Lilly, AUG 4, 2023, View Source [SID1234633819]). The study met its primary endpoint, demonstrating a statistically significant and clinically meaningful improvement in progression-free survival (PFS). This result was based on a pre-specified interim efficacy analysis conducted by an independent data monitoring committee (IDMC). Adverse events observed on Retevmo were generally consistent with those identified across the previously reported Retevmo development program (LIBRETTO-001, LIBRETTO-121, LIBRETTO-321).

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The labeling for Retevmo contains warnings and precautions for hepatotoxicity (evidence of liver dysfunction), interstitial lung disease (ILD)/pneumonitis, hypertension, QT interval prolongation, hemorrhagic events, hypersensitivity, tumor lysis syndrome, risk of impaired wound healing, hypothyroidism, and embryo-fetal toxicity.

LIBRETTO-431 is a Phase 3, randomized, open-label trial evaluating Retevmo versus platinum-based chemotherapy (cisplatin or carboplatin) plus pemetrexed with or without pembrolizumab, which is a current first-line standard of care option for patients with EGFR/ALK-negative NSCLC. LIBRETTO-431 is the first randomized trial comparing the safety and effectiveness of a targeted therapy to a PD-1 inhibitor plus chemotherapy in a biomarker selected patient population.

"The LIBRETTO-431 trial aims to answer an important question about the selection of initial treatment for people with advanced RET fusion-positive NSCLC and these results suggest Retevmo should be considered a first-line standard of care," said David Hyman, M.D., chief medical officer, Loxo@Lilly. "Additionally, this clinically meaningful achievement of improved outcomes underscores the importance of timely and comprehensive genomic testing to inform initial treatment decisions for all patients with NSCLC. The results of this study provide further confirmation that RET status – like EGFR, ALK, and others in the family of lung cancer oncogenic drivers – should be known prior to initiating therapy. We look forward to sharing these data in more detail with the oncology community."

These results build on the data from LIBRETTO-001, the largest clinical trial of patients with RET-driven cancers treated with a RET inhibitor, which spans 16 countries and 85 sites, and includes a dose escalation phase (Phase 1) and a dose expansion phase (Phase 2). In this trial, Retevmo demonstrated clinically meaningful and durable responses across a variety of tumor types in patients with RET-driven cancers.

NSCLC accounts for about 85 percent of all lung cancer diagnoses in the U.S., of which approximately 50 percent have actionable biomarkers. RET fusions have been identified in approximately one to two percent of all NSCLC cases.

Full results from the LIBRETTO-431 trial will be presented at an upcoming medical meeting, submitted to a peer-reviewed journal, and discussed with health authorities.

About LIBRETTO-431
LIBRETTO-431 is a randomized Phase 3 clinical trial of patients with treatment-naïve RET fusion-positive NSCLC. The trial enrolled 261 patients with advanced or metastatic RET fusion-positive NSCLC who had received no prior systemic therapy for metastatic disease. Enrolled trial participants were randomized 2:1 to receive either selpercatinib or platinum-based (carboplatin or cisplatin) and pemetrexed therapy with or without pembrolizumab as initial treatment of their advanced or metastatic RET fusion-positive NSCLC. RET fusions may be identified using local testing. This trial’s primary endpoint is progression-free survival (PFS) and secondary endpoints include overall survival (OS), overall response rate (ORR), duration of response (DoR), and intracranial ORR. For patients randomized to the control arm, crossover was allowed at progression.

About Retevmo (selpercatinib, 40 mg & 80 mg capsules)
Retevmo (selpercatinib, formerly known as LOXO-292) (pronounced reh-TEHV-moh) is a highly selective and potent RET kinase inhibitor with central nervous system (CNS) activity. Retevmo may affect both tumor cells and healthy cells, which can result in side effects. RET-driver alterations are predominantly mutually exclusive from other oncogenic drivers. Retevmo is a U.S. FDA-approved oral prescription medicine, 120 mg or 160 mg dependent on weight (<50 kg or ≥50 kg, respectively), taken twice daily until disease progression or unacceptable toxicity.

IMPORTANT SAFETY INFORMATION FOR RETEVMO (selpercatinib)

Hepatotoxicity: Serious hepatic adverse reactions occurred in 3% of patients treated with Retevmo. Increased aspartate aminotransferase (AST) occurred in 59% of patients, including Grade 3 or 4 events in 11% and increased alanine aminotransferase (ALT) occurred in 55% of patients, including Grade 3 or 4 events in 12%. Monitor ALT and AST prior to initiating Retevmo, every 2 weeks during the first 3 months, then monthly thereafter and as clinically indicated. Withhold, reduce dose, or permanently discontinue Retevmo based on the severity.

Severe, life-threatening, and fatal interstitial lung disease (ILD)/pneumonitis can occur in patients treated with Retevmo. ILD/pneumonitis occurred in 1.8% of patients who received Retevmo, including 0.3% with Grade 3 or 4 events, and 0.3% with fatal reactions. Monitor for pulmonary symptoms indicative of ILD/pneumonitis. Withhold Retevmo and promptly investigate for ILD in any patient who presents with acute or worsening of respiratory symptoms which may be indicative of ILD (e.g., dyspnea, cough, and fever). Withhold, reduce dose, or permanently discontinue Retevmo based on severity of confirmed ILD.

Hypertension occurred in 41% of patients, including Grade 3 hypertension in 20% and Grade 4 in one (0.1%) patient. Overall, 6.3% had their dose interrupted and 1.3% had their dose reduced for hypertension. Treatment-emergent hypertension was most commonly managed with anti-hypertension medications. Do not initiate Retevmo in patients with uncontrolled hypertension. Optimize blood pressure prior to initiating Retevmo. Monitor blood pressure after 1 week, at least monthly thereafter, and as clinically indicated. Initiate or adjust anti-hypertensive therapy as appropriate. Withhold, reduce dose, or permanently discontinue Retevmo based on the severity.

Retevmo can cause concentration-dependent QT interval prolongation. An increase in QTcF interval to >500 ms was measured in 7% of patients and an increase in the QTcF interval of at least 60 ms over baseline was measured in 20% of patients. Retevmo has not been studied in patients with clinically significant active cardiovascular disease or recent myocardial infarction. Monitor patients who are at significant risk of developing QTc prolongation, including patients with known long QT syndromes, clinically significant bradyarrhythmias, and severe or uncontrolled heart failure. Assess QT interval, electrolytes, and thyroid-stimulating hormone (TSH) at baseline and periodically during treatment, adjusting frequency based upon risk factors including diarrhea. Correct hypokalemia, hypomagnesemia, and hypocalcemia prior to initiating Retevmo and during treatment. Monitor the QT interval more frequently when Retevmo is concomitantly administered with strong and moderate CYP3A inhibitors or drugs known to prolong QTc interval. Withhold and dose reduce or permanently discontinue Retevmo based on the severity.

Serious, including fatal, hemorrhagic events can occur with Retevmo. Grade ≥3 hemorrhagic events occurred in 3.1% of patients treated with Retevmo including 4 (0.5%) patients with fatal hemorrhagic events, including cerebral hemorrhage (n=2), tracheostomy site hemorrhage (n=1), and hemoptysis (n=1). Permanently discontinue Retevmo in patients with severe or life-threatening hemorrhage.

Hypersensitivity occurred in 6% of patients receiving Retevmo, including Grade 3 hypersensitivity in 1.9%. The median time to onset was 1.9 weeks (range: 5 days to 2 years). Signs and symptoms of hypersensitivity included fever, rash and arthralgias or myalgias with concurrent decreased platelets or transaminitis. If hypersensitivity occurs, withhold Retevmo and begin corticosteroids at a dose of 1 mg/kg prednisone (or equivalent). Upon resolution of the event, resume Retevmo at a reduced dose and increase the dose of Retevmo by 1 dose level each week as tolerated until reaching the dose taken prior to onset of hypersensitivity. Continue steroids until patient reaches target dose and then taper. Permanently discontinue Retevmo for recurrent hypersensitivity.

Tumor lysis syndrome (TLS) occurred in 0.6% of patients with medullary thyroid carcinoma receiving Retevmo. Patients may be at risk of TLS if they have rapidly growing tumors, a high tumor burden, renal dysfunction, or dehydration. Closely monitor patients at risk, consider appropriate prophylaxis including hydration, and treat as clinically indicated.

Impaired wound healing can occur in patients who receive drugs that inhibit the vascular endothelial growth factor (VEGF) signaling pathway. Therefore, Retevmo has the potential to adversely affect wound healing. Withhold Retevmo for at least 7 days prior to elective surgery. Do not administer for at least 2 weeks following major surgery and until adequate wound healing. The safety of resumption of Retevmo after resolution of wound healing complications has not been established.

Retevmo can cause hypothyroidism. Hypothyroidism occurred in 13% of patients treated with Retevmo; all reactions were Grade 1 or 2. Hypothyroidism occurred in 13% of patients (50/373) with thyroid cancer and 13% of patients (53/423) with other solid tumors including NSCLC. Monitor thyroid function before treatment with Retevmo and periodically during treatment. Treat with thyroid hormone replacement as clinically indicated. Withhold Retevmo until clinically stable or permanently discontinue Retevmo based on severity.

Based on data from animal reproduction studies and its mechanism of action, Retevmo can cause fetal harm when administered to a pregnant woman. Administration of selpercatinib to pregnant rats during organogenesis at maternal exposures that were approximately equal to those observed at the recommended human dose of 160 mg twice daily resulted in embryolethality and malformations. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment with Retevmo and for 1 week after the last dose. There are no data on the presence of selpercatinib or its metabolites in human milk or on their effects on the breastfed child or on milk production. Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with Retevmo and for 1 week after the last dose.

Severe adverse reactions (Grade 3-4) occurring in ≥20% of patients who received Retevmo in LIBRETTO-001, were hypertension (20%), diarrhea (5%), prolonged QT interval (4.8%), dyspnea (3.1%), fatigue (3.1%), hemorrhage (2.6%), abdominal pain (2.5%), vomiting (1.8%), headache (1.4%), nausea (1.1%), constipation (0.8%), edema (0.8%), rash (0.6%), and arthralgia (0.3%).

Serious adverse reactions occurred in 44% of patients who received Retevmo. The most frequently reported serious adverse reactions (in ≥2% of patients) were pneumonia, pleural effusion, abdominal pain, hemorrhage, hypersensitivity, dyspnea, and hyponatremia.

Fatal adverse reactions occurred in 3% of patients; fatal adverse reactions included sepsis (n=6), respiratory failure (n=5), hemorrhage (n=4), pneumonia (n=3), pneumonitis (n=2), cardiac arrest (n=2), sudden death (n=1), and cardiac failure (n=1).

Common adverse reactions (all grades) occurring in ≥20% of patients who received Retevmo in LIBRETTO-001, were edema (49%), diarrhea (47%), fatigue (46%), dry mouth (43%), hypertension (41%), abdominal pain (34%), rash (33%), constipation (33%), nausea (31%), headache (28%), cough (24%), vomiting (22%), dyspnea (22%), hemorrhage (22%), arthralgia (21%), and prolonged QT interval (21%).

Laboratory abnormalities (all grades ≥20%; Grade 3-4) worsening from baseline in patients who received Retevmo in LIBRETTO-001, were increased AST (59%; 11%), decreased calcium (59%; 5.7%), increased ALT (56%; 12%), decreased albumin (56%; 2.3%), increased glucose (53%; 2.8%), decreased lymphocytes (52%; 20%), increased creatinine (47%; 2.4%), decreased sodium (42%; 11%), increased alkaline phosphatase (40%; 3.4%), decreased platelets (37%; 3.2%), increased total cholesterol (35%; 1.7%), increased potassium (34%; 2.7%), decreased glucose (34%; 1.0%), decreased magnesium (33%; 0.6%), increased bilirubin (30%; 2.8%), decreased hemoglobin (28%; 3.5%), and decreased neutrophils (25%; 3.2%).

Concomitant use of acid-reducing agents decreases selpercatinib plasma concentrations which may reduce Retevmo anti-tumor activity. Avoid concomitant use of proton-pump inhibitors (PPIs), histamine-2 (H2) receptor antagonists, and locally-acting antacids with Retevmo. If coadministration cannot be avoided, take Retevmo with food (with a PPI) or modify its administration time (with a H2 receptor antagonist or a locally-acting antacid).

Concomitant use of strong and moderate CYP3A inhibitors increases selpercatinib plasma concentrations which may increase the risk of Retevmo adverse reactions including QTc interval prolongation. Avoid concomitant use of strong and moderate CYP3A inhibitors with Retevmo. If concomitant use of a strong or moderate CYP3A inhibitor cannot be avoided, reduce the Retevmo dosage as recommended and monitor the QT interval with ECGs more frequently.

Concomitant use of strong and moderate CYP3A inducers decreases selpercatinib plasma concentrations which may reduce Retevmo anti-tumor activity. Avoid coadministration of Retevmo with strong and moderate CYP3A inducers.

Concomitant use of Retevmo with CYP2C8 and CYP3A substrates increases their plasma concentrations which may increase the risk of adverse reactions related to these substrates. Avoid coadministration of Retevmo with CYP2C8 and CYP3A substrates where minimal concentration changes may lead to increased adverse reactions. If coadministration cannot be avoided, follow recommendations for CYP2C8 and CYP3A substrates provided in their approved product labeling.

Retevmo is a P-glycoprotein (P-gp) inhibitor. Concomitant use of Retevmo with P-gp substrates increases their plasma concentrations, which may increase the risk of adverse reactions related to these substrates. Avoid coadministration of Retevmo with P-gp substrates where minimal concentration changes may lead to increased adverse reactions. If coadministration cannot be avoided, follow recommendations for P-gp substrates provided in their approved product labeling.

No dosage modification is recommended for patients with mild to severe renal impairment (estimated Glomerular Filtration Rate [eGFR] ≥15 to 89 mL/min, estimated by Modification of Diet in Renal Disease [MDRD] equation). A recommended dosage has not been established for patients with end-stage renal disease.

Reduce the dose when administering Retevmo to patients with severe hepatic impairment (total bilirubin greater than 3 to 10 times upper limit of normal [ULN] and any AST). No dosage modification is recommended for patients with mild or moderate hepatic impairment. Monitor for Retevmo-related adverse reactions in patients with hepatic impairment.

Please see full Prescribing Information for Retevmo.

On August 4, 2023 BridgeBio Pharma, Inc. (Nasdaq: BBIO) ("BridgeBio" or the "Company"), a commercial-stage biopharmaceutical company focused on genetic diseases and cancers, reported that on August 02, 2023, the compensation committee of BridgeBio’s board of directors granted seven new employees restricted stock units for an aggregate of 26,657 shares of the Company’s common stock (Press release, BridgeBio, AUG 4, 2023, View Source [SID1234633818]). One-fourth of the shares underlying each employee’s restricted stock units will vest on August 16, 2024, with one-twelfth of the remaining shares underlying each such employee’s restricted stock units vesting on a quarterly basis thereafter, in each case, subject to each such employee’s continued employment with the Company or one of its subsidiaries on such vesting dates. All of the above-described awards were made under BridgeBio’s Amended and Restated 2019 Inducement Equity Plan (the "Plan").

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The above-described awards were each granted as an inducement material to the employees entering into employment with the Company in accordance with Nasdaq Listing Rule 5635(c)(4) and were granted pursuant to the terms of the Plan. The Plan was adopted by BridgeBio’s board of directors in November 2019 and amended and restated on February 10, 2023.

On August 4, 2023 BioCryst Pharmaceuticals, Inc. (Nasdaq: BCRX) reported that the compensation committee of BioCryst’s board of directors granted seven newly-hired employees stock options to purchase an aggregate of 38,600 shares, and restricted stock units (RSUs) covering an aggregate of 26,450 shares, of BioCryst common stock (Press release, BioCryst Pharmaceuticals, AUG 4, 2023, View Source [SID1234633817]). The options and RSUs were granted as of July 31, 2023, as inducements material to each employee entering into employment with BioCryst. The options and RSUs were granted in accordance with Nasdaq Listing Rule 5635(c)(4).

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The options have an exercise price of $7.39 per share, which is equal to the closing price of BioCryst common stock on the grant date. The options and RSUs vest in four equal annual installments beginning on the one-year anniversary of the grant date, in each case subject to the new employee’s continued service with the company. Each stock option has a 10-year term. The options and RSUs are subject to the terms and conditions of BioCryst’s Inducement Equity Incentive Plan and a stock option agreement or restricted stock unit agreement, as applicable, covering the grant.