Merus Announces U.S. FDA Acceptance and Priority Review of Biologics License Application for Zeno for the Treatment of NRG1+ NSCLC and PDAC

On May 6, 2024 Merus N.V. (Nasdaq: MRUS) (Merus, the Company, we, or our), a clinical-stage oncology company developing innovative, full-length multispecific antibodies (Biclonics and Triclonics), reported that the U.S. Food and Drug Administration (FDA) has accepted for priority review a Biologics License Application (BLA) for the bispecific antibody zenocutuzumab (Zeno) in patients with neuregulin 1 fusion (NRG1+) non-small cell lung (NSCLC) and NRG1+ pancreatic (PDAC) cancer (Press release, Merus, MAY 6, 2024, View Source [SID1234642696]).

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"FDA acceptance of our first BLA represents an important achievement for Merus and an important potential treatment opportunity for patients with NRG1+ cancer, a disease with poor prognosis and high unmet need," said Dr. Andrew Joe, Chief Medical Officer at Merus. "Zenocutuzumab has the potential to be the first and only targeted therapy for patients with NRG1+ lung and pancreatic cancer, and may offer a substantial improvement over currently available therapies."

The BLA includes a comprehensive clinical data package, including data from the phase 1/2 eNRGy trial, which is investigating the safety and anti-tumor activity of Zeno monotherapy in NRG1+ NSCLC, PDAC and other solid tumors. Data from the open-label trial were presented previously at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2021 Annual Meeting, and subsequently updated at ASCO (Free ASCO Whitepaper) 2022 and the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2023.

The FDA has granted Breakthrough Therapy Designation (BTD) to Zeno for the treatment of patients with advanced unresectable or metastatic NRG1+ pancreatic cancer following progression with prior systemic therapy or who have no satisfactory alternative treatment options. Additionally, the FDA has granted BTD to Zeno for the treatment of patients with advanced unresectable or metastatic NRG1+ NSCLC, following progression with prior systemic therapy.

Zeno is currently under clinical development, and its safety and efficacy have not been fully evaluated by any regulatory authority.

About Zeno

Zeno is a Biclonics that utilizes the Merus Dock & Block mechanism to inhibit the neuregulin/HER3 tumor-signaling pathway in solid tumors with NRG1 fusions (NRG1+ cancer). Through its unique mechanism of binding to HER2 and potently blocking the interaction of HER3 with its ligand NRG1 or NRG1-fusion proteins, Zeno has the potential to be particularly effective against NRG1+ cancer. In preclinical studies, Zeno potently inhibits HER2/HER3 heterodimer formation thereby inhibiting oncogenic signaling pathways, leading to inhibition of tumor cell proliferation and blocking tumor cell survival. In clinical studies, Zeno has demonstrated anti-tumor activity in multiple types of NRG1+ cancer, including NRG1+ NSCLC and NRG1+ PDAC.

About NRG1 Fusions

The NRG1 gene encodes neuregulin (also known as heregulin), the ligand for HER3. Fusions between NRG1 and partner genes are rare, tumorigenic genomic events occurring in certain cancer types including NSCLC and PDAC.

Plus Therapeutics Announces Private Placement Financing of up to $18 Million

On May 6, 2024 Plus Therapeutics, Inc. (Nasdaq: PSTV) (the "Company"), a clinical-stage pharmaceutical company developing targeted radiotherapeutics with advanced platform technologies for central nervous system (CNS) cancers, reported that it has entered into a securities purchase agreement with new institutional investors and Company insiders to raise up to approximately $18 million in gross proceeds, including initial upfront funding of approximately $6.5 million, and up to an additional approximately $11.5 million upon cash exercise of accompanying warrants at the election of the investors (Press release, Plus Therapeutics, MAY 6, 2024, View Source [SID1234642695]).

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The financing includes participation from AIGH Capital Management LLC with additional participation from new healthcare-focused institutional investors as well as certain Company insiders.

"The capital from this transaction, funded by experienced institutional investors and insiders, in conjunction with existing cash and grant support, provides the company with up to approximately $34 million in cash runway, assuming full exercise of the warrants, to support achievement of our corporate objectives," said Marc Hedrick, M.D. President and CEO.

Pursuant to terms of the securities purchase agreement, the Company will issue up to an aggregate of 3,238,627 shares of its common stock (or pre-funded warrants in lieu thereof) and accompanying warrants to purchase up to an aggregate of 6,477,254 shares of its common stock at a combined purchase price of $2.022 per share and accompanying warrants, in accordance with the "Minimum Price" requirement as defined in the Nasdaq rules. The accompanying warrants will consist of two series:

Series A warrants to purchase up to an aggregate of 3,238,627 shares of common stock at an exercise price of $1.772 per share for an aggregate of up to approximately $5.7 million and will be exercisable until the five-year anniversary of closing of the financing.
Series B warrants to purchase up to 3,238,627 shares of common stock at an exercise price of $1.772 per share for an aggregate of up to approximately $5.7 million. The Series B warrants will be exercisable until the one-year anniversary of the effectiveness of a registration statement covering the resale of shares of common stock underlying the Series B warrants.
In lieu of shares of common stock, certain investors are purchasing pre-funded warrants at a combined purchase price of $2.021 per pre-funded warrant and accompanying warrants, which equals the purchase price per share of common stock and accompanying warrant, less the $0.001 per share exercise price of each pre-funded warrant. The private placement is expected to close on or about May 8, 2024, subject to satisfaction of customary closing conditions.

The Company intends to use the upfront net proceeds from the private placement for general corporate purposes and to fund the Re-SPECT LM clinical development program.

This offer and sale of the foregoing securities are being made in a transaction not involving a public offering, and the securities have not been registered under the Securities Act of 1933, as amended (the "Securities Act"), or applicable state securities laws. Accordingly, the securities may not be reoffered or resold in the United States except pursuant to an effective registration statement or an applicable exemption from the registration requirements of the Securities Act and such applicable state securities laws. The Company has agreed to file a registration statement with the SEC registering the resale of the shares of common stock purchased in the financing and shares of common stock underlying the warrants.

This press release does not constitute an offer to sell or the solicitation of an offer to buy the securities, nor shall there be any sale of the securities in any state in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of such state. Any offering of the securities under the resale registration statement will only be made by means of a prospectus.

Sandoz reports first quarter 2024 sales

On May 6, 2024 Sandoz (SIX:SDZ/OTCQX:SDZNY), the global leader in generic and biosimilar medicines, reported net sales for the first quarter 2024 (Press release, Sandoz, MAY 6, 2024, View Source [SID1234642694]). Net sales were USD 2.5 billion, an increase of 6% in constant currencies compared to the same quarter of the prior year. Biosimilars saw another quarter of double-digit net sales growth, an increase of 21% in constant currencies. Generics sales remained in line with prior year levels.

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Richard Saynor, Chief Executive Officer of Sandoz, said: "We saw a strong start to the year as we report our 10th consecutive quarter of topline growth. The momentum in our business continues as demonstrated by double-digit growth in biosimilars and a positive contribution by all regions."

Mr. Saynor continued: "Biosimilars are a key element of performance, driven by strong results in our existing portfolio, demand for our recently launched product Hyrimoz (adalimumab-adaz) in the US and the recent acquisition of CIMERLI (ranibizumab-eqrn), which closed in early March. Generics remained in line with the strong prior year sales. Looking forward, we are confident in our ability to continue to grow our top line and meet our full-year net sales guidance of mid-single digits in constant currencies."

FIRST QUARTER NET SALES RESULTS
Net sales for the first quarter were USD 2.5 billion, up 6% in constant currencies, compared to the first quarter of 2023. Volume contributed 10 percentage points of growth, partially offset by price erosion of 4 percentage points. Biosimilars were a key driver of growth in the quarter, while generics remained in line with the strong prior year sales.

Net sales by business

Three months ended March 31 Change %
USD millions unless indicated otherwise 2024 2023 USD cc*
Generics 1869 1868 0 1
Biosimilars 623 516 21 21
Net sales to third parties 2492 2384 5 6
*Constant currencies

Generics overview
Net sales for the first quarter were USD 1.9 billion, up 1% in constant currencies, compared to the first quarter of 2023. Solid volume demand was partly offset by the impact from the withdrawal of apixaban in the Netherlands following a court decision in August 2023, an exceptional cough and cold season in the first half of 2023 and the timing of new launches in the US.

Biosimilars overview
Net sales for the first quarter were USD 623 million, up 21% in constant currencies, compared to the first quarter of 2023. This strong double-digit biosimilar growth reflects the ongoing launch of Hyrimoz high-concentration formulation, the acquisition of CIMERLI as well as continued strong demand for our first-ever biosimilar, Omnitrope.

Net sales by region

Three months ended March 31 Change %
USD millions unless indicated otherwise 2024 2023 USD cc
Europe 1326 1270 4 2
North America 524 496 6 6
International 642 618 4 12
Net sales to third parties 2492 2384 5 6
Europe overview
Net sales for the first quarter were USD 1.3 billion, up 2% in constant currencies, compared to the first quarter of 2023. Generic volume growth remained positive despite a strong prior year comparison from peak sales of apixaban and an exceptional cough and cold season. Biosimilars showed strong sales growth, led by demand for Omnitrope and contribution from the recent launch of Tyruko (natalizumab) in several key countries.

North America overview
Net sales for the first quarter were USD 524 million, up 6% in constant currencies, compared to the first quarter of 2023. Growth was driven by the ongoing launch of Hyrimoz in the US, continued demand for Omnitrope, the acquisition of CIMERLI which closed in early March, and the transfer of mature brands from our former parent in the fourth quarter of 2023. This was partly offset by a decline in generics sales due to the timing of new launches in the US.

International overview
Net sales for the first quarter were USD 642 million, up 12% in constant currencies, compared to the first quarter of 2023. This was primarily a result of strong volume growth across both generics and biosimilars, the acquisition of Mycamine in the prior year and favorable price dynamics.

GUIDANCE 2024
The company reiterates its full-year 2024 guidance, expecting net sales to grow mid-single digit in constant currencies versus prior year and core EBITDA margin around 20%.

FIRST QUARTER STRATEGIC MILESTONES
On January 31, we announced the launch of Tyruko in Germany. Developed by Polpharma Biologics, Tyruko is the first and only biosimilar to treat relapsing remitting multiple sclerosis. The availability of Tyruko is a crucial milestone in improving access to effective and safe therapies for those in Europe that need them most.

On March 4, we announced the completion of the US biosimilar CIMERLI acquisition from Coherus BioSciences, Inc, ahead of anticipated timelines. The acquisition builds on the leading Sandoz ophthalmic platform in the US and lays an even stronger foundation for future product launches.

On March 5, we announced that Remco Steenbergen, currently a Sandoz Board member, will become a member of the Executive Committee and take on the responsibility of Sandoz CFO as of July 1, 2024. Remco will succeed Colin Bond who will step down from his position as of June 30, 2024, and retire in January 2025 per Swiss employment practice. Colin will be available for transition as a senior advisor through the end of 2024.

On March 5, we also announced that the US Food and Drug Administration (FDA) approved Wyost (denosumab-bbdz) and Jubbonti (denosumab-bbdz), the first and only FDA-approved denosumab biosimilars, to treat all indications of the reference medicines including osteoporosis and cancer-related skeletal events.

KEY LINKS
Webcast – Live at 9am CET
Analyst Call Presentation
Analyst Consensus

NON-IFRS MEASURES IN THIS DOCUMENT AS DEFINED BY SANDOZ
Sandoz uses certain non-IFRS metrics when measuring performance, especially when measuring current period results against prior periods, including core results, constant currencies and free cash flow. Despite the use of these measures by management in setting goals and measuring Sandoz performance, these are non-IFRS measures that have no standardized meaning prescribed by IFRS Accounting Standards. As a result, such measures have limits in their usefulness to investors. Because of their non-standardized definitions, the non-IFRS measures (unlike IFRS measures) may not be comparable to the calculation of similar measures of other companies. These non-IFRS measures are presented solely to permit investors to more fully understand how Sandoz management assesses underlying performance. These non-IFRS measures are not, and should not be viewed as, a substitute for IFRS measures, and should be viewed in conjunction with IFRS financials. As an internal measure of Group performance, these non-IFRS measures have limitations, and Sandoz performance management process is not solely restricted to these metrics.

The definitions of the non-IFRS financial metrics as used by Sandoz are as follows:

Core results
Sandoz core results – including core EBITDA, core operating income, core net income and core earnings per share – exclude fully:

The amortization and impairment charges of intangible assets other than software;
Net gains and losses on fund investments and equity securities valued at fair value through profit and loss;
Certain acquisition and divestment- related items;
Tax liabilities for uncertain tax positions.
The following items that exceed a threshold of USD 25 million are also excluded:

Integration- and divestment- related income and expenses;
Divestment gains and losses;
Restructuring charges/releases and related items;
Legal related items;
Impairments of property, plant and equipment, software and financial assets;
And income and expense items that management deems exceptional and that are or are expected to accumulate within the year to be over a USD 25 million threshold. Income tax impacts of such items are also excluded from core measures.
Sandoz believes that investor understanding of its performance is enhanced by disclosing core measures of performance because, since core measures exclude items that can vary significantly from year to year, they enable a better comparison of business performance across years. For this same reason, Sandoz uses these core measures in addition to IFRS and other measures as important factors in assessing its performance.

The following are examples of how these core measures are utilized:

In addition to monthly reports containing financial information prepared under IFRS, senior management receives a monthly analysis incorporating these core measures;
Annual budgets are prepared for both IFRS and core measures.
As an internal measure of Sandoz performance, the core results measures have limitations, and the Sandoz performance management process is not solely restricted to these metrics.

A limitation of the core results measures is that they provide a view of the Sandoz operations without including all events during a period, such as the effects of an acquisition, divestment, or amortization/impairments of purchased intangible assets, impairments to property, plant and equipment and restructurings and related items.

Constant currencies
Changes in the relative values of non-US currencies to the US dollar can affect Sandoz financial results and financial position. To provide additional information that may be useful to investors, including changes in sales volume, Sandoz presents information about its net sales and various values relating to operating and net income that are adjusted for such foreign currency effects. Constant currency calculations have the goal of eliminating two exchange rate effects so that an estimate can be made of underlying changes in the consolidated income statement excluding the impact of fluctuations in exchanges rates:

The impact of translating the income statements of consolidated entities from their non-USD functional currencies to USD;
The impact of exchange rate movements on the major transactions of consolidated entities performed in currencies other than their functional currency.
Sandoz calculates constant currency measures by translating the current year’s foreign currency values for sales and other income statement items into USD (excluding the IAS 29 "Financial Reporting in Hyperinflationary Economies" adjustments to the local currency income statements of subsidiaries operating in hyperinflationary economies), using the average exchange rates from the prior year and comparing them to the prior year values in USD. Sandoz uses these constant currency measures in evaluating its performance, since they may assist the Group in evaluating its ongoing performance from year to year. However, in performing its evaluation, Sandoz also considers equivalent measures of performance that are not affected by changes in the relative value of currencies.

EBITDA
Sandoz defines earnings before interest, tax, depreciation, and amortization (EBITDA) as operating income, excluding depreciation of property, plant and equipment and right-of-use assets, amortization of intangible assets, impairments of property, plant and equipment, right-of-use assets, and intangible assets.

Core EBITDA margin
Sandoz defines core EBITDA margin as the percentage of core EBITDA over net sales to third parties. It is an indicator to measure the profitability of the Group.

Currencies
References to "USD" or "U.S. dollars" are to the lawful currency of the United States of America.

Rounding
Certain figures contained in the media release, including financial information presented in millions or thousands, certain operating data and percentages describing financial information or market shares, have been subject to rounding. Accordingly, in certain instances, the amounts shown as totals in tables or elsewhere may not conform exactly to the arithmetic total of the figures that precede them. In addition, certain percentages reflect calculations based upon the underlying information prior to rounding and, accordingly, may not conform exactly to the percentages that would be derived if the relevant calculations were based upon the rounded numbers.

Regeneron Announces Investor Conference Presentations

On May 6, 2024 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported that it will webcast management participation as follows (Press release, Regeneron, MAY 6, 2024, View Source [SID1234642692]):

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RBC Capital Markets Global Healthcare Conference at 9:00 a.m. ET on Tuesday, May 14, 2024
Jefferies Global Healthcare Conference at 8:30 a.m. ET on Wednesday, June 5, 2024
Goldman Sachs 45th Annual Global Healthcare Conference at 8:00 a.m. ET on Tuesday, June 11, 2024

The sessions may be accessed from the "Investors & Media" page of Regeneron’s website at View Source Replays and transcripts of the webcasts will be archived on the Company’s website for at least 30 days.

Day One Reports First Quarter 2024 Financial Results and Corporate Progress

On May 6, 2024 Day One Biopharmaceuticals (Nasdaq: DAWN) ("Day One" or the "Company"), a commercial-stage biopharmaceutical company dedicated to developing and commercializing targeted therapies for people of all ages with life-threatening diseases, reported its first quarter 2024 financial results and highlighted recent corporate achievements (Press release, Day One, MAY 6, 2024, View Source [SID1234642691]).

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"We are excited that OJEMDA is now approved and available here in the U.S., and we are grateful to the members of the pediatric brain tumor community whose support of the program has been invaluable," said Jeremy Bender, Ph.D., chief executive officer of Day One. "Our team is focused on executing our U.S. launch, on advancing our other programs, and on exploring opportunities to expand our pipeline."

Program Highlights


In April 2024, the Company received U.S. Food and Drug Administration (FDA) accelerated approval of OJEMDA (tovorafenib), the first and only FDA approved therapy for the treatment of pediatric patients 6 months of age and older with relapsed or refractory pediatric low-grade glioma (pLGG) harboring a BRAF fusion or rearrangement, or BRAF V600 mutation.


With OJEMDA now available and the first prescriptions written, patients have begun enrolling in EveryDay Support From Day OneTM, a comprehensive program that offers personalized services for OJEMDA patients and their care teams, including insurance coverage support, financial assistance options and educational resources throughout the treatment journey.


The pivotal Phase 3 FIREFLY-2/LOGGIC clinical trial evaluating tovorafenib as a front-line therapy in patients aged 6 months to 25 years with pLGG continues to enroll in the United States, Canada, Europe, Australia and Asia, with more than 90 sites activated.


Patient enrollment continues in the Phase 1b/2 substudy (102b) of the FIRELIGHT-1 trial evaluating the combination of tovorafenib with the Company’s investigational MEK inhibitor, pimasertib.

Corporate Highlights and Upcoming Milestones


The Company received a rare pediatric disease priority review voucher from the FDA upon OJEMDA’s approval.


Results from the FIRELIGHT-1 Phase 1b and next steps are expected in the second half of 2024.

First Quarter 2024 Financial Highlights


Cash Position: Cash, cash equivalents and short-term investments totaled $317.9 million on March 31, 2024. Based on Day One’s current operating plan, management believes it has sufficient capital resources to fund anticipated operations into 2026.


R&D Expenses: Research and development expenses were $40.2 million for the first quarter of 2024 compared to $27.8 million for the first quarter of 2023. The increase was primarily due to additional employee compensation costs, a payment for the buyback of priority review voucher obligation, and increased clinical trial and manufacturing activities related to Day One’s lead product, OJEMDA.


G&A Expenses: General and administrative expenses were $26.6 million for the first quarter of 2024 compared to $18.0 million for the first quarter of 2023. The increase was primarily due to additional employee compensation costs, ongoing commercial buildout, and increased professional service expenses to support company growth.


Net Loss: Net loss totaled $62.4 million for the first quarter of 2024 with non-cash stock compensation expense of $12.6 million, compared to $42.4 million for the first quarter of 2023 with non-cash stock compensation expense of $9.4 million.

Upcoming Events


2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, May 31-June 4, 2024
o
Abstract #10036 titled "Type II RAF inhibitor tovorafenib in relapsed/refractory pediatric low-grade glioma (pLGG): Reversible decreases in growth velocity in the phase 2 FIREFLY-1 trial" will be presented in a poster session on Saturday, June 1 from 1:30-4:30 pm CDT in Hall A


Goldman Sachs 45th Annual Global Healthcare Conference, June 10-13, 2024


21st International Symposium on Pediatric Neuro-Oncology (ISPNO), June 28-29, 2024

About OJEMDA

OJEMDA (tovorafenib) is a Type II RAF kinase inhibitor of mutant BRAF V600, wild-type BRAF, and wild-type CRAF kinases.

OJEMDA is indicated for the treatment of patients 6 months of age and older with relapsed or refractory pediatric low-grade glioma (LGG) harboring a BRAF fusion or rearrangement, or BRAF V600 mutation. This indication is approved under accelerated approval based on response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

Tovorafenib is under evaluation as a therapy for patients with pLGG requiring front-line treatment (Phase 3 FIREFLY-2/LOGGIC). It is also being studied in combination with the MEK inhibitor pimasertib for adolescent and adult patient populations with recurrent or progressive solid tumors with MAPK pathway alterations (FIRELIGHT-1).

Tovorafenib was granted Breakthrough Therapy and Rare Pediatric Disease designations by the FDA for the treatment of patients with pLGG harboring an activating RAF alteration, and it was evaluated by the FDA under priority review. Tovorafenib has also received Orphan Drug designation from the FDA for the treatment of malignant glioma and from the European Commission for the treatment of glioma.

For more information, please visit www.ojemda.com.