On May 2, 2024 Ascendis Pharma A/S (Nasdaq: ASND) reported financial results for the first quarter ended March 31, 2024, and provided a business update (Press release, Ascendis Pharma, MAY 2, 2024, View Source [SID1234642575]).

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"With SKYTROFA revenue more than doubling in the U.S. compared to the first quarter of 2023, and our successful initial launch of YORVIPATH in Germany and Austria, we believe Ascendis is on the path to achieving sustainable growth and operating cash flow breakeven on a quarterly basis by the end of 2024," said Jan Mikkelsen, Ascendis Pharma’s President and Chief Executive Officer. "Our achievements this quarter give me further confidence that all elements are in place to deliver three independent Endocrinology Rare Disease blockbuster products and a strong pipeline in larger therapeutic areas such as Oncology, Ophthalmology, and Metabolic Diseases as outlined in Vision 2030."

Select Highlights & Anticipated 2024 Milestones

TransCon hGH:
(lonapegsomatropin, approved as SKYTROFA in the U.S., EU, European Economic Area (EEA) countries, and Great Britain)
First quarter 2024 SKYTROFA revenue totaled €65 million, a 106% year over year increase with a steady quarter to quarter increase in treated patients.
Full year 2024 SKYTROFA revenue expected to be €320 million to €340 million (based on average 2023 exchange rates).
Plan to submit a supplemental Biologics License Application to FDA for adult growth hormone deficiency (GHD), in the third quarter of 2024.
Topline results from Phase 2 trial in Turner syndrome expected in the fourth quarter of 2024.
TransCon PTH:
(palopegteriparatide, approved as YORVIPATH in the EU, EEA countries, and Great Britain)
Commercial rollout of YORVIPATH continues in Germany and Austria with an estimated 55 doctors writing prescriptions and ~100 patients receiving commercial product as of March 31. First quarter YORVIPATH revenue totaled €1.5 million reflecting first two months of delivery to patients.
In the U.S., Prescription Drug User Fee Act (PDUFA) date of May 14, 2024; if approved, U.S. commercial launch planned in the third quarter of 2024.
Granted marketing authorization for the treatment of adults with chronic hypoparathyroidism and orphan drug status in Great Britain.
TransCon CNP:
(navepegritide)
Topline data from pivotal ApproaCH Trial expected in the fourth quarter of 2024, and plan to submit a New Drug Application to FDA for children with achondroplasia (age 2-11 years) in the same quarter.
Expect to initiate and complete enrollment in the combination TransCon hGH and TransCon CNP COACH trial of children with achondroplasia (ages 2-11) during the second quarter of 2024; topline Week 26 data expected in the fourth quarter of 2024.
Oncology Programs
New data from the ongoing Phase 1/2 IL-Believe Trial has been accepted for a poster presentation at the American Society for Clinical Oncology (ASCO) (Free ASCO Whitepaper) May 31-June 4. The presentation will provide initial data from the combination of TransCon IL-2 β/γ and TransCon TLR7/8 Agonists in patients with melanoma who have progressed on anti-PD1 therapy.
During the fourth quarter of 2024, plan to provide a clinical update from the Phase 2 indication-specific, dose expansion cohorts from our TransCon IL-2 β/γ and TransCon TLR7/8 Agonist clinical trials.
Financial Update and Outlook Based on Current Plans
As of March 31, 2024, Ascendis Pharma had cash, cash equivalents, and marketable securities totaling €320 million compared to €399 million as of December 31, 2023.
Full year 2024 SKYTROFA revenue expected to be €320 million to €340 million (based on average 2023 exchange rates).
Expect total operating expenses (SG&A and R&D) of approximately €600 million for 2024.
Expect to be operating cash flow breakeven on a quarterly basis by the end of 2024.
First Quarter 2024 Financial Results
Total revenue for the first quarter of 2024 was €95.9 million compared to €33.6 million during the same period for 2023. The increase was primarily attributable to higher SKYTROFA revenue of €65.0 million compared to €31.6 million in the same period last year and non-cash license revenue of €24.8 million related to the license agreement with Eyconis in January 2024.

Total Revenue (In EUR’000s) Three Months Ended March 31,
2024 2023
Revenue from external customers
Commercial sale of products 66,499 31,551
Licenses 24,770 614
Other 4,625 1,424
Total revenue from external customers 95,894 33,589

Research and development (R&D) costs for the first quarter of 2024 were €70.7 million compared to €106.1 million during the same period in 2023. The 33% decline was largely tied to lower external development costs for TransCon hGH, TransCon PTH (including a reversal of prior period write-downs of pre-launch inventories) and Oncology programs, partially offset by an increase in TransCon CNP costs.

Selling, general, and administrative (SG&A) expenses for the first quarter of 2024 were €66.8 million compared to €66.5 million during the same period in 2023. Higher employee costs, including the impact from commercial expansion, partly offset by lower external pre-launch and administrative expenses.

Total operating expenses for the first quarter of 2024 were €137.5 million compared to €172.7 million during the same period in 2023.

Net finance expenses for the first quarter of 2024 were €73.6 million compared to a net finance income of €35.3 million during the same period in 2023.

For the first quarter of 2024, Ascendis Pharma reported a net loss of €131.0 million, or €2.30 per share (basic and diluted) compared to a net loss of €110.9 million, or €1.98 per share (basic and diluted) for the same period in 2023.

As of March 31, 2024, Ascendis Pharma had cash, cash equivalents, and marketable securities totaling €320.2 million compared to €399.4 million as of December 31, 2023. As of March 31, 2024, Ascendis Pharma had 58,224,419 ordinary shares outstanding, including 881,730 ordinary shares represented by ADSs held by the company.

Conference Call and Webcast Information
Ascendis Pharma will host a conference call and webcast today at 4:30 pm Eastern Time (ET) to discuss its first quarter 2024 financial results.

Those who would like to participate may access the live webcast here, or register in advance for the teleconference here. The link to the live webcast will also be available on the Investors & News section of the Ascendis Pharma website at View Source A replay of the webcast will be available on this section of the Ascendis Pharma website shortly after conclusion of the event for 30 days.

On May 2, 2024 Amgen reported financial results for the first quarter 2024 (Press release, Amgen, MAY 2, 2024, View Source [SID1234642573]).

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"With many of our innovative products delivering strong growth and promising new medicines advancing through our pipeline, we are excited about delivering attractive long-term growth," said Robert A. Bradway, chairman and chief executive officer.

Key results include:
•For the first quarter, total revenues increased 22% to $7.4 billion in comparison to the first quarter of 2023. Product sales grew 22%, driven by 25% volume growth.
◦Ten products delivered at least double-digit volume growth in the first quarter, including Repatha (evolocumab), TEZSPIRE (tezepelumab-ekko), EVENITY (romosozumab-aqqg), BLINCYTO (blinatumomab), and TAVNEOS (avacopan).
◦U.S. volume grew 29% and ex-U.S. volume grew 17%.
◦Our performance included $914 million of sales from our Horizon Therapeutics (Horizon) acquisition, driven by several first-in-class, early-in-lifecycle medicines, including TEPEZZA (teprotumumab-trbw), KRYSTEXXA (pegloticase) and UPLIZNA (inebilizumab-cdon).
◦Excluding sales from Horizon, our product sales grew 6%, driven by volume growth of 9%.
•GAAP loss per share was $0.21 for the first quarter of 2024 compared with GAAP earnings per share (EPS) of $5.28 for the first quarter of 2023, driven by a mark-to-market loss on our BeiGene, Ltd. equity investment and higher operating expenses, including higher amortization expense from Horizon-acquired assets and incremental expenses from Horizon, partially offset by higher revenues.
◦GAAP operating income decreased from $1.9 billion to $1.0 billion, and GAAP operating margin decreased 19.0 percentage points to 13.9%.
•Non-GAAP EPS decreased 1% from $3.98 to $3.96, due to higher operating and interest expenses driven by the Horizon acquisition, partially offset by higher revenues.
◦Non-GAAP operating income increased from $2.8 billion to $3.1 billion, and non-GAAP operating margin decreased 5.1 percentage points to 43.2%.
•The Company generated $0.5 billion of free cash flow for the first quarter of 2024 versus $0.7 billion in the first quarter of 2023. This decrease was driven by an $800 million tax deposit, partially offset by timing of working capital items.

On May 2, 2024 Alpha-9 Oncology (Alpha-9), a clinical stage company developing radiopharmaceuticals for the treatment of cancer patients worldwide, reported that the first participant has been dosed in the Phase 1 study evaluating 68Ga-A9-3202, a radiodiagnostic targeting melanocortin 1 receptor (MC1R) for the imaging of locally advanced or metastatic melanoma (Press release, Alpha9 Oncology, MAY 2, 2024, View Source [SID1234642574]). MC1R expression is known to be elevated in malignant melanoma and other types of skin cancers.

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The Phase 1 multi-centre study is evaluating the tumour uptake and normal tissue distribution of 68Ga-A9-3202 in participants with locally advanced or metastatic melanoma (ACTRN12624000085572). This new agent, in conjunction with current standard CT or PET/CT imaging, will be used in the future to identify patients suitable to receive a novel radiotherapeutic agent targeting MC1R also developed by Alpha-9.

"This agent is the first step in our effort to develop radiopharmaceuticals targeting MC1R for the treatment of patients with advanced or metastatic melanoma," commented Dr. Ovid Trifan, Chief Medical Officer at Alpha-9. "We’re excited to advance our portfolio of molecules further into the clinic."

On May 2, 2024 Agios Pharmaceuticals, Inc. (Nasdaq: AGIO), a leader in cellular metabolism and PK activation pioneering therapies for rare diseases, reported business highlights and financial results for the first quarter ended March 31, 2024 (Press release, Agios Pharmaceuticals, MAY 2, 2024, View Source [SID1234642572]).

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"We were delighted to report positive data from the Phase 3 ENERGIZE study of mitapivat in non-transfusion-dependent thalassemia and look forward to announcing topline data from the Phase 3 ENERGIZE-T study in transfusion-dependent thalassemia in the second quarter of this year," said Brian Goff, chief executive officer at Agios. "Mitapivat has the potential to become the first therapy approved for all thalassemia subtypes, and our commercial organization is actively preparing for a potential launch next year. Beyond thalassemia, we look forward to the RISE UP Phase 3 readout in sickle cell disease next year, with potential for approval in 2026, as we progress toward our vision of becoming a leading rare disease company with a potential multi-billion-dollar franchise in PK activation."

First Quarter 2024 and Recent Highlights

PYRUKYND Revenues: Generated $8.2 million in net revenue for the first quarter of 2024, a 15 percent sequential increase from the fourth quarter of 2023, primarily driven by increased patient demand. A total of 188 unique patients have completed prescription enrollment forms, representing an increase of 6 percent over the fourth quarter of 2023. A total of 120 patients are on PYRUKYND therapy, a 10 percent increase from the fourth quarter of 2023.
Thalassemia: Announced positive results from the Phase 3 ENERGIZE study of mitapivat in adults with non-transfusion-dependent alpha- or beta-thalassemia.
Earlier-Stage Pipeline: Dosed the first participants in the Phase 1 study of AG-181 for the treatment of phenylketonuria (PKU).
Environment, Social, and Governance (ESG): Published 2024 ESG Report, which provides corporate sustainability disclosures for the period Jan. 1, 2023 to Dec. 31, 2023.
Other: Servier announced FDA filing acceptance and priority review for a new drug application (NDA) for vorasidenib for the treatment of IDH-mutant diffuse glioma. The FDA has assigned a Prescription Drug User Fee Act (PDUFA) action date of August 20, 2024. As part of the divestiture of Agios’ oncology business to Servier, Agios retains rights to a potential $200 million milestone upon FDA approval of vorasidenib and 15% royalties on potential U.S. net sales.
Key Upcoming Milestones & Priorities

Agios expects to execute on the following additional key milestones and priorities by the end of 2024:

Thalassemia: Two key milestones for the year, including reporting topline data from the Phase 3 ENERGIZE-T study of mitapivat in transfusion-dependent thalassemia (Q2) and filing for FDA approval of mitapivat in thalassemia (year-end).
Sickle Cell Disease: Complete enrollment in the Phase 3 portion of the RISE UP study of mitapivat (year-end).
Pediatric PK Deficiency: Complete enrollment in the Phase 3 ACTIVATE-kids study of mitapivat (mid-year). Report topline data from Phase 3 ACTIVATE kids-T study (now mid-year).
Lower-risk Myelodysplastic Syndromes: Dose first patient in Phase 2b study of AG-946 (mid-year).
Other: Potential approval of Servier’s vorasidenib for the treatment of IDH-mutant diffuse glioma. The FDA has assigned a PDUFA action date of August 20, 2024. Agios retains certain economic rights, as described above.
First Quarter 2024 Financial Results

Revenue: Net product revenue from sales of PYRUKYND for the first quarter of 2024 was $8.2 million, compared to $5.6 million for the first quarter of 2023.

Cost of Sales: Cost of sales for the first quarter of 2024 was $0.6 million.

Research and Development (R&D) Expenses: R&D expenses were $68.6 million for the first quarter of 2024, compared to $67.3 million for the first quarter of 2023. The year-over-year comparison reflects an increase in process development expenses, offset by a decrease in workforce-related expenditures.

Selling, General and Administrative (SG&A) Expenses: SG&A expenses were $31.0 million for the first quarter of 2024 compared to $28.4 million for the first quarter of 2023. The year-over-year increase was primarily attributable to an increase in commercial-related activities as we prepare for the potential approval of PYRUKYND in thalassemia.

Net Loss: Net loss was $81.5 million for the first quarter of 2024 compared to $81.0 million for the first quarter of 2023.

Cash Position and Guidance: Cash, cash equivalents and marketable securities as of March 31, 2024, were $714.3 million compared to $806.4 million as of December 31, 2023. Agios expects that its cash, cash equivalents and marketable securities together with anticipated product revenue, interest income and vorasidenib milestone will enable the company to fund its operating expenses and capital expenditures at least into 2026. This does not include cash inflows, which could extend runway beyond 2026, including potential royalties or monetization of royalties from vorasidenib, commercializing mitapivat outside of the U.S. through one or more partnerships, or other potential strategic business or financial agreements.

Conference Call Information

Agios will host a conference call and live webcast with slides today at 8:00 a.m. ET to discuss first quarter 2024 financial results and recent business highlights. The live webcast can be accessed under "Events & Presentations" in the Investors section of the company’s website at www.agios.com. The archived webcast will be available on the company’s website beginning approximately two hours after the event.

On May 2, 2024 AstraZeneca reported positive high-level results from an interim analysis of the ECHO Phase III trial showed AstraZeneca’s Calquence (acalabrutinib) in combination with standard-of-care chemoimmunotherapy, bendamustine and rituximab, demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) versus standard of care in previously untreated adult patients with mantle cell lymphoma (MCL) (Press release, AstraZeneca, MAY 2, 2024, View Source [SID1234642536]).

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A trend was observed in favour of Calquence plus chemoimmunotherapy for the secondary endpoint of overall survival (OS). The OS data were not mature at the time of this analysis and the trial will continue to assess OS.

MCL is a rare and typically aggressive form of non-Hodgkin lymphoma (NHL), often diagnosed as a late-stage disease, resulting when B-lymphocytes mutate into malignant cells within a region of the lymph node known as the mantle zone.1,2 It is estimated that there are more than 27,500 patients diagnosed with MCL worldwide.3,4

Michael Wang, MD, Puddin Clarke Endowed Professor, Director of Mantle Cell Lymphoma Program of Excellence, Co-Director of Clinical Trials at MD Anderson Cancer Center in Houston, US and principal investigator in the trial, said: "These positive progression-free survival results from the ECHO Phase III trial could provide a new standard of care for patients with mantle cell lymphoma. Incorporating Calquence into the first-line mantle cell lymphoma setting would give many more patients the opportunity to benefit from the robust efficacy and strong safety profile we’ve seen with this medicine."

Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: "These impactful results in mantle cell lymphoma show that bringing Calquence to the first-line setting significantly delays disease progression and, for the first time, shows potential to extend survival. The improvement in progression-free survival together with the differentiated safety profile of Calquence are both important as we strive to transform outcomes earlier in the course of disease treatment."

The safety and tolerability of Calquence was consistent with its known safety profile, and no new safety signals were identified.

The data will be presented at a forthcoming medical meeting and shared with global regulatory authorities.

As part of an extensive clinical development programme, AstraZeneca is currently evaluating Calquence alone and in combination for the treatment of multiple B-cell blood cancers, including chronic lymphocytic leukaemia (CLL), MCL, and diffuse large B-cell lymphoma.

Calquence has been used to treat more than 80,000 patients worldwide and is approved for the treatment of CLL and small lymphocytic lymphoma (SLL) in the US, approved for CLL in the EU and many other countries worldwide and approved in Japan and China for relapsed or refractory CLL and SLL. Calquence is also approved in the US, China and several other countries for the treatment of adult patients with MCL who have received at least one prior therapy. Calquence is not currently approved for the treatment of MCL in Japan or the EU.

Notes

Mantle cell lymphoma
MCL is an uncommon subtype of B-cell non-Hodgkin lymphoma.5 MCL comprises about 3-6% of non-Hodgkin lymphomas, with an annual incidence of 0.5 per 100,000 population in Western countries; in the US, it is estimated that approximately 4,000 new cases of MCL are diagnosed each year.5,6 While MCL patients initially respond to treatment, patients do tend to relapse.5

ECHO
ECHO is a randomised, double-blind, placebo-controlled, multi-centre Phase III trial evaluating the efficacy and safety of Calquence plus bendamustine and rituximab compared to standard of care chemoimmunotherapy (bendamustine and rituximab) in adult patients at or over 65 years of age (n=598) with previously untreated MCL.7 In the experimental arms, patients were randomised 1:1 to receive either Calquence or placebo administered orally twice per day, on 28 day treatment cycles, plus bendamustine on days 1 and 2 and rituximab on day 1. After six cycles of Calquence or placebo in combination with bendamustine and rituximab, patients receive Calquence or placebo plus maintenance rituximab for two years and then either Calquence or placebo only until disease progression.7

The primary endpoint is PFS and key secondary endpoints include OS, overall response rate (ORR), duration of response (DoR) and time to response (TTR).7 The trial includes 27 countries across North and South America, Europe, Asia and Oceania.7

The ECHO trial was conducted from 2017 to 2023 continuing through the COVID-19 pandemic. Patients with blood cancer remain at a disproportionately high risk of severe outcomes from COVID-19, including hospitalisation and death compared to the general population.8

Calquence
Calquence (acalabrutinib) is a next-generation, selective inhibitor of Bruton’s tyrosine kinase (BTK). Calquence binds covalently to BTK, thereby inhibiting its activity.9 In B cells, BTK signalling results in activation of pathways necessary for B-cell proliferation, trafficking, chemotaxis and adhesion.