On October 31, 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 financial results for the third quarter and provided a business update (Press release, Merus, OCT 31, 2024, View Source [SID1234647610]).

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"I’m encouraged by our continued operational effectiveness, with phase 3 trials accelerating for petosemtamab in both 1L and 2/3L recurrent/metastatic head and neck cancer. I believe petosemtamab has the potential to offer both a first and best in class chemo-free option for these patients," said Bill Lundberg, M.D., President, Chief Executive Officer of Merus. "We look forward to providing an update on petosemtamab’s monotherapy efficacy, duration and safety in 2L+ HNSCC this December at ESMO (Free ESMO Whitepaper) Asia and, in the near future, providing more information on a number of important potential near term catalysts in 2025."

Petosemtamab (MCLA-158: EGFR x LGR5 Biclonics): Solid Tumors
LiGeR-HN1 phase 3 trial in 1L head and neck squamous cell carcinoma (HNSCC) and LiGeR-HN2 phase 3 trial in 2/3L HNSCC enrolling; phase 2 trial in 2L metastatic colorectal cancer (mCRC) enrolling; clinical data update on 2L+ HNSCC planned for ESMO (Free ESMO Whitepaper) Asia in December 2024

In the third quarter, Merus announced the first patient was dosed in LiGeR-HN1, a phase 3 trial evaluating the efficacy and safety of petosemtamab in combination with pembrolizumab in 1L HNSCC expressing PD-L1 (CPS≥1) compared to pembrolizumab. In this trial, patients will be randomized to petosemtamab plus pembrolizumab or pembrolizumab monotherapy. This was detailed in our press release, Merus Announces First Patient Dosed in LiGeR-HN1, a Phase 3 Trial Evaluating Petosemtamab in Combination with Pembrolizumab in 1L r/m HNSCC (September 30, 2024).

Merus provided an interim clinical update on petosemtamab with pembrolizumab in 1L r/m HNSCC at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting 2024, demonstrating a 67% response rate among 24 evaluable patients. The oral presentation was detailed in our press release, Merus’ Petosemtamab in Combination with Pembrolizumab Interim Data Demonstrates Robust Response Rate and Favorable Safety Profile in 1L r/m HNSCC (May 28, 2024).

Merus also provided an interim clinical update on petosemtamab monotherapy in 2L+ HNSCC at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2023, demonstrating a 37% response rate among 43 evaluable patients. The oral presentation was detailed in our press release (April 17, 2023). Merus plans to provide updated efficacy, durability and safety data of this cohort along with clinical data from the dose optimization cohort evaluating petosemtamab monotherapy 1500 or 1100 mg dose levels in 2L+HNSCC. This was detailed in our press release, Merus Announces Abstract Accepted for Presentation at the ESMO (Free ESMO Whitepaper) Asia Congress 2024 (September 17, 2024).

Merus believes a randomized registration trial in HNSCC with an overall response rate endpoint could potentially support accelerated approval and the overall survival results from the same study could potentially verify its clinical benefit to support regular approval.

In the third quarter, Merus announced the first patient was dosed in a phase 2 trial evaluating petosemtamab in combination with standard chemotherapy in 2L mCRC. This was detailed in our press release, Merus Announces First Patient Dosed in Phase 2 Trial of Petosemtamab in 2L CRC (July 8, 2024).

Zenocutuzumab (Zeno or MCLA-128: HER2 x HER3 Biclonics): NRG1 fusion-positive (NRG1+) lung, pancreatic and other solid tumors
Zeno BLA for treatment of NRG1+ non-small cell lung cancer (NSCLC) and pancreatic cancer (PDAC) accepted for priority review by the FDA

The FDA has accepted for priority review a Biologics License Application (BLA) for the bispecific antibody Zeno in patients with NRG1+ NSCLC and PDAC cancer. This acceptance was detailed in our press release Merus Announces U.S. FDA Acceptance and Priority Review of Biologics License Application for Zeno for the Treatment of NRG1+ NSCLC and PDAC (May 6, 2024).

Merus believes that obtaining a commercialization partnership agreement is an important step in bringing Zeno to patients with NRG1+ cancer, if approved.

MCLA-129 (EGFR x c-MET Biclonics): Solid Tumors
Investigation of MCLA-129 is ongoing in METex14 NSCLC; phase 2 trial in combination with chemotherapy in 2L+ EGFR mutant (EGFRm) NSCLC enrolling

In the third quarter, Merus announced the first patients were dosed in the phase 2 trial evaluating MCLA-129 in combination with chemotherapy in 2L+ EGFRm NSCLC, with a cohort receiving MCLA-129 and paclitaxel and carboplatin, and another cohort receiving MCLA-129 and docetaxel. We also remain interested in partnering MCLA-129 to sufficiently resource the development of MCLA-129 and the potential benefit it may have for patients.

MCLA-129 is subject to a collaboration and license agreement with Betta Pharmaceuticals Co. Ltd. (Betta), which permits Betta to develop MCLA-129 and potentially commercialize exclusively in China, while Merus retains global rights outside of China.

MCLA-145 (CD137 x PD-L1 Biclonics): Solid Tumors

Investigation continues of the phase 1 trial of MCLA-145 in combination with pembrolizumab

Collaborations

Incyte Corporation
Since 2017, Merus has been working with Incyte Corporation (Incyte) under a global collaboration and license agreement focused on the research, discovery and development of bispecific antibodies utilizing Merus’ proprietary Biclonics technology platform. For each program under the collaboration, Merus receives reimbursement for research activities and is eligible to receive potential development, regulatory and commercial milestones and sales royalties for any products, if approved.

Eli Lilly and Company
In January 2021, Merus and Eli Lilly and Company (Lilly) announced a research collaboration and exclusive license agreement to develop up to three CD3-engaging T-cell re-directing bispecific antibody therapies utilizing Merus’ Biclonics platform and proprietary CD3 panel along with the scientific and rational drug design expertise of Lilly. The collaboration is progressing well with three programs ongoing at various stages of preclinical development.

Gilead Sciences
In March 2024, Merus and Gilead Sciences announced a collaboration to discover novel antibody based trispecific T-cell engagers using Merus’ patented Triclonics platform. Under the terms of the agreement, Merus will lead early-stage research activities for two programs, with an option to pursue a third. Gilead will have the right to exclusively license programs developed under the collaboration after the completion of select research activities. If Gilead exercises its option to license any such program from the collaboration, Gilead will be responsible for additional research, development and commercialization activities for such program. Merus received an equity investment by Gilead of $25 million in Merus common shares and an upfront payment of $56 million.

Ono Pharmaceutical
In 2018, the Company granted Ono Pharmaceutical Co., Ltd. (Ono) an exclusive, worldwide, royalty-bearing license, with the right to sublicense, research, test, make, use and market a limited number of bispecific antibody candidates based on Merus’ Biclonics technology platform directed to an undisclosed target combination. During the third quarter of 2024, Merus achieved and received a milestone payment based on the filing of an Investigational New Drug (IND) application in Japan.

Cash Runway, existing cash, cash equivalents and marketable securities expected to fund Merus’ operations into 2028

As of September 30, 2024, Merus had $782.9 million cash, cash equivalents and marketable securities. Based on the Company’s current operating plan, the existing cash, cash equivalents and marketable securities are expected to fund Merus’ operations into 2028.

Third Quarter 2024 Financial Results

Collaboration revenue for the three months ended September 30, 2024 increased by $0.8 million as compared to the three months ended September 30, 2023, primarily as a result of increases in amortization of upfront deferred revenue. The change in exchange rates did not significantly impact collaboration revenue.

Research and development expense for the three months ended September 30, 2024 increased by $26.5 million as compared to the three months ended September 30, 2023, primarily as a result of increases in external clinical services and drug manufacturing expenses.

General and administrative expense for the three months ended September 30, 2024 increased by $8.2 million as compared to the three months ended September 30, 2023, primarily as a result of increases in personnel related expenses, facilities, depreciation expense and consulting expenses.

Collaboration revenue for the nine months ended September 30, 2024 decreased by $8.0 million as compared to the nine months ended September 30, 2023, primarily as a result of decreases in milestone revenue and amortization of deferred revenue.

Research and development expense for the nine months ended September 30, 2024 increased by $51.0 million as compared to the nine months ended September 30, 2023, primarily as a result of increases in external clinical services and drug manufacturing expenses.

General and administrative expense for the nine months ended September 30, 2024 increased by $15.5 million as compared to the nine months ended September 30, 2023, primarily as a result of increases in personnel related expenses and consulting expenses.

Other income (loss), net consists of interest earned and fees paid on our cash and cash equivalents held on account, accretion of investment earnings and net foreign exchange (losses) gains on our foreign denominated cash, cash equivalents and marketable securities. Other gains or losses relate to the issuance and settlement of financial instruments.

On October 31, 2024 HOOKIPA Pharma Inc. (NASDAQ: HOOK) ("HOOKIPA" or the "Company"), a clinical-stage biopharmaceutical company developing next generation immunotherapeutics for the treatment of cancer and serious infectious diseases, reported that updated Phase 2 data for eseba-vec (HB200) plus pembrolizumab in first-line recurrent/metastatic HPV16-positive head and neck cancer will be presented as a late-breaking poster presentation at the 39th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) (SITC 2024), taking place in Houston, Texas from November 8-10, 2024 (Press release, Hookipa Pharma, OCT 31, 2024, View Source [SID1234647609]).

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The poster will be presented by Alan Ho, MD, PhD, Chief of the Head and Neck Oncology Service at Memorial Sloan Cancer Center (MSKCC), a clinical collaborator of HOOKIPA.

Details of the poster presentation are:

Abstract Title: Eseba-vec (HB-200) plus pembrolizumab as first-line treatment of recurrent/metastatic HPV16-positive head and neck cancer: updated results in PD-L1 CPS ≥20 patients
Presenter: Dr. Alan Ho, MSKCC
Session Date: Saturday, November 9, 2024
Session Time: 9:00 AM – 8:00 PM CDT
Late Breaking Abstract Number: 1480

The poster will be available on November 9, 2024 on the HOOKIPA website on the "Scientific Publications" tab of the "Our Science" page.

About Eseba-vec
Eseba-vec (also known as HB-200) is an investigational immunotherapeutic agent being evaluated for HPV16 positive cancers. The first indication for eseba-vec is for the potential treatment of patients with HPV16+ recurrent/metastatic oropharyngeal squamous cell carcinoma (R/M OPSCC) with a PDL1 CPS of 20 or higher, in combination with pembrolizumab, in the first line (1L) setting. Eseba-vec has received Fast Track Designation from the U.S. Food and Drug Administration and PRIME designation from the European Medicines Agency for the treatment of 1L HPV16+ OPSCC. Eseba-vec was developed using HOOKIPA’s proprietary arenavirus platform.

On October 31, 2024 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported financial results for the third quarter of 2024 and provided a business update (Press release, Regeneron, OCT 31, 2024, View Source [SID1234647608]).

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"Regeneron had a strong third quarter marked by 11% revenue growth. We continued to deepen the impact of our commercialized medicines this quarter, with ongoing leadership for our retinal franchise, expanded global reach of Libtayo, and notable growth from Dupixent," said Leonard S. Schleifer, M.D., Ph.D., Board co-Chair, President and Chief Executive Officer of Regeneron. "Over one million patients around the globe are currently being treated with Dupixent, with more to come following the approvals for COPD in the U.S., Europe and China. Our remarkably diverse clinical portfolio now includes approximately 40 product candidates and many pivotal studies underway. We continue to invest in the world-class research and development engine that drives our scientific and clinical productivity, with data expected over the next twelve months in diseases as varied as non-small cell lung cancer, thrombosis, retinal vein occlusion, severe allergy, COPD, melanoma, and obesity."

Financial Highlights

($ in millions, except per share data) Q3 2024 Q3 2023 % Change
Total revenues $ 3,721 $ 3,363 11 %
GAAP net income $ 1,341 $ 1,008 33 %
GAAP net income per share – diluted $ 11.54 $ 8.89 30 %
Non-GAAP net income(a) $ 1,462 $ 1,329 10 %
Non-GAAP net income per share – diluted(a) $ 12.46 $ 11.59 8 %

"Our strong third quarter financial performance was highlighted by double-digit revenue growth and continued investment in our growing pipeline," said Christopher Fenimore, Senior Vice President, Finance and Chief Financial Officer of Regeneron. "We remain focused on translating cutting-edge science into differentiated medicines that have the greatest potential to serve patients, while deploying capital with the goal of maximizing shareholder returns, primarily through investing in innovation coupled with opportunistic share repurchases."

Business Highlights

Key Pipeline Progress
Regeneron has approximately 40 product candidates in clinical development, including a number of marketed products for which it is investigating additional indications. Updates from the clinical pipeline include:

EYLEA HD (aflibercept) 8 mg

The Company announced positive three-year (156-week) data from an extension study of the Phase 3 PHOTON trial in patients with diabetic macular edema (DME). At three years, the longer-term data showed the vast majority of EYLEA HD patients who entered the extension study sustained the visual gains and anatomic improvements achieved by the end of the second year. Of the EYLEA HD patients who completed the full 156 weeks of treatment, 48% were assigned a dosing interval of ≥20 weeks at the end of the third year. The results were presented at the American Academy of Ophthalmology (AAO) Annual Meeting.
Dupixent (dupilumab)

In September 2024, the U.S. Food and Drug Administration (FDA) approved Dupixent as an add-on maintenance treatment for adults with inadequately controlled COPD and an eosinophilic phenotype. With this approval, Dupixent is the first biologic medicine approved in the United States, European Union (EU), and China to treat these patients.
In September 2024, the FDA approved Dupixent as an add-on maintenance treatment for adolescents aged 12 to 17 years with inadequately controlled chronic rhinosinusitis with nasal polyposis (CRSwNP).
The European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion recommending expanded approval of Dupixent in the EU to treat children aged 1 to 11 years with eosinophilic esophagitis (EoE). The European Commission (EC) is expected to announce a final decision in the coming months.
The Company and Sanofi announced that a confirmatory Phase 3 trial met the primary and key secondary endpoints for the investigational treatment of patients with uncontrolled, biologic-naïve CSU receiving background therapy with antihistamines, showing treatment with Dupixent resulted in a nearly 50% reduction in itch and urticaria activity scores from baseline. This positive trial confirms results from the first Phase 3 trial of Dupixent in this setting and these data supported the recent resubmission of a supplemental Biologics License Application (sBLA) to the FDA.
The Company and Sanofi announced that a Phase 3 trial in bullous pemphigoid met the primary and all key secondary endpoints evaluating the investigational use in adults with moderate-to-severe disease. In the trial, five times more Dupixent patients achieved sustained disease remission compared to those on placebo. This trial will support global regulatory submissions, including the anticipated fourth quarter 2024 submission in the United States.
Oncology Programs

In August 2024, the EC approved Ordspono (odronextamab) to treat adult patients with relapsed or refractory (R/R) follicular lymphoma (FL) or R/R diffuse large B-cell lymphoma (DLBCL), after two or more lines of systemic therapy.
The Company announced five-year results from the final pre-specified overall survival (OS) analysis of a Phase 3 trial, which evaluated Libtayo (cemiplimab) monotherapy versus chemotherapy as a first-line treatment for certain adults with advanced non-small cell lung cancer (NSCLC) with ≥50% PD-L1 expression. The results were presented at the IASLC 2024 World Conference on Lung Cancer.
The Company submitted a regulatory application in Japan for Libtayo for first-line advanced NSCLC (monotherapy and chemotherapy combination).
A Phase 2 study for Libtayo in neoadjuvant NSCLC was initiated.
The Company presented new, two-year results at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Annual Meeting, evaluating the investigational combination of fianlimab, an antibody to LAG-3, and Libtayo in adults with advanced melanoma across three independent expansion cohorts of a first-in-human, multi-cohort trial. These longer-term results show high clinical activity, including deepening responses, per a blinded independent central review.
In August 2024, the FDA issued a Complete Response Letter (CRL) for the BLA for linvoseltamab, a bispecific antibody targeting BCMA and CD3, in R/R multiple myeloma that has progressed after at least three prior therapies. The sole approvability issue identified is related to findings from a pre-approval inspection at a third-party fill/finish manufacturer. Resolution of this issue will be required for both FDA and EC regulatory approvals.
Other Programs

A Phase 3 study was initiated for pozelimab, an antibody to C5, in combination with cemdisiran, an siRNA therapy, in geographic atrophy.
A Phase 2 study for REGN7999, an antibody to TMPRSS6, for the treatment of iron overload in patients with beta-thalassemia was initiated.
Third Quarter 2024 Financial Results

Revenues

($ in millions) Q3 2024 Q3 2023 % Change
Net product sales:
EYLEA HD – U.S. $ 392 $ 43 *
EYLEA – U.S. 1,145 1,448 (21 %)
Total EYLEA HD and EYLEA – U.S. 1,537 1,491 3 %
Libtayo – Global 289 232 25 %
Praluent – U.S. 53 40 33 %
Evkeeza – U.S. 32 19 68 %
Inmazeb – Global 35 4 *
Total net product sales 1,946 1,786 9 %

Collaboration revenue:
Sanofi 1,263 1,065 19 %
Bayer 391 377 4 %
Other 6 (3 ) *
Other revenue 114 138 (17 %)
Total revenues $ 3,720 $ 3,363 11 %

* Percentage not meaningful

Total EYLEA HD and EYLEA net product sales in the U.S. increased 3% in the third quarter of 2024 compared to the third quarter of 2023. EYLEA HD was approved by the FDA in August 2023 and net product sales in the third quarter of 2024 were driven by the transition of patients from other anti-VEGF products, including EYLEA, as well as new patients naïve to anti-VEGF therapy. Net product sales of EYLEA in the third quarter of 2024 were adversely impacted by a lower net selling price compared to the third quarter of 2023. In addition, third quarter 2024 total EYLEA HD and EYLEA net product sales were favorably impacted by approximately $40 million as a result of higher wholesaler inventory levels for EYLEA HD at the end of the third quarter of 2024 compared to the end of the second quarter of 2024, partially offset by lower wholesaler inventory levels for EYLEA.

Sanofi collaboration revenue increased in the third quarter of 2024, compared to the third quarter of 2023, due to an increase in the Company’s share of profits from commercialization of antibodies, which were $1.09 billion in the third quarter of 2024, compared to $863 million in the third quarter of 2023. The change in the Company’s share of profits from commercialization of antibodies was driven by higher profits associated with an increase in Dupixent sales. Sanofi collaboration revenue in the third quarter of 2023 was positively impacted by the recognition of the final $50 million sales-based milestone.

Refer to Table 4 for a summary of collaboration revenue.

Operating Expenses

GAAP %
Change
Non-GAAP(a) %
Change
($ in millions) Q3 2024 Q3 2023 Q3 2024 Q3 2023
Research and development (R&D) $ 1,272 $ 1,075 18 % $ 1,146 $ 954 20 %
Acquired in-process research and development (IPR&D) $ 56 $ 100 (44 %) * * n/a
Selling, general, and administrative (SG&A) $ 714 $ 641 11 % $ 613 $ 534 15 %
Cost of goods sold (COGS) $ 262 $ 225 16 % $ 217 $ 181 20 %
Cost of collaboration and contract manufacturing (COCM) $ 229 $ 212 8 % * * n/a
Other operating expense (income), net $ 8 $ (1 ) ** $ — * **

* GAAP and non-GAAP amounts are equivalent as no non-GAAP adjustments have been recorded.
** Percentage not meaningful
GAAP and non-GAAP R&D expenses increased in the third quarter of 2024, compared to the third quarter of 2023, driven by the advancement of the Company’s clinical pipeline, including late-stage oncology programs, and higher headcount and headcount-related costs.
Acquired IPR&D for the third quarter of 2024 included a $45 million development milestone in connection with the Company’s collaboration agreement with Sonoma Biotherapeutics, Inc. Acquired IPR&D expense in the third quarter of 2023 related to a $100 million development milestone in connection with the Company’s collaboration with Alnylam Pharmaceuticals, Inc.
GAAP and non-GAAP SG&A expenses increased in the third quarter of 2024, compared to the third quarter of 2023, due to higher commercialization-related expenses to support the Company’s launch of EYLEA HD and higher headcount and headcount-related costs partly related to the Company’s international commercial expansion.
GAAP and non-GAAP COGS increased in the third quarter of 2024, compared to the third quarter of 2023, primarily due to higher start-up costs for the Company’s Rensselaer, New York fill/finish facility.
Other Financial Information

GAAP other income (expense) included the recognition of net unrealized gains on equity securities of $135 million in the third quarter of 2024, compared to $100 million of net unrealized losses in the third quarter of 2023. GAAP and Non-GAAP other income (expense) also included interest income of $187 million in the third quarter of 2024, compared to $134 million in the third quarter of 2023.

In the third quarter of 2024, the Company’s GAAP effective tax rate (ETR) was 10.2%, compared to 9.3% in the third quarter of 2023. The GAAP ETR increased in the third quarter of 2024, compared to the third quarter of 2023, due to a lower benefit from income earned in foreign jurisdictions with tax rates lower than the U.S. federal statutory rate. In the third quarter of 2024, the non-GAAP ETR was 10.7%, compared to 11.9% in the third quarter of 2023.

GAAP net income per diluted share was $11.54 in the third quarter of 2024, compared to $8.89 in the third quarter of 2023. Non-GAAP net income per diluted share was $12.46 in the third quarter of 2024, compared to $11.59 in the third quarter of 2023. A reconciliation of the Company’s GAAP to non-GAAP results is included in Table 3 of this press release.

During the third quarter of 2024, the Company repurchased shares of its common stock and recorded the cost of the shares, or $738 million, as Treasury Stock. As of September 30, 2024, $2.9 billion remained available for share repurchases under the Company’s share repurchase program.

2024 Financial Guidance(c)

The Company’s full year 2024 financial guidance consists of the following components:

2024 Guidance
Prior Updated
GAAP R&D $5.020–$5.170 billion $5.055–$5.145 billion
Non-GAAP R&D(a) $4.500–$4.600 billion $4.525–$4.575 billion
GAAP SG&A $2.920–$3.060 billion $2.930–$3.020 billion
Non-GAAP SG&A(a) $2.550–$2.650 billion $2.550–$2.600 billion
GAAP gross margin on net product sales(d) Approximately 86% Unchanged
Non-GAAP gross margin on net product sales(a)(d) Approximately 89% Unchanged
COCM(e)* $850–$910 million $860–$900 million
Capital expenditures* $750–$820 million $700–$740 million
GAAP effective tax rate 8%–9% Unchanged
Non-GAAP effective tax rate(a) 10%–11% Unchanged

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

A reconciliation of full year 2024 GAAP to non-GAAP financial guidance is included below:

Projected Range
($ in millions) Low High
GAAP R&D $ 5,055 $ 5,145
Stock-based compensation expense 520 540
Acquisition and integration costs 10 30
Non-GAAP R&D $ 4,525 $ 4,575

GAAP SG&A $ 2,930 $ 3,020
Stock-based compensation expense 340 360
Acquisition, integration, and other costs 40 60
Non-GAAP SG&A $ 2,550 $ 2,600

GAAP gross margin on net product sales Approximately 86% Approximately 86%
Stock-based compensation expense 1 % 1 %
Intangible asset amortization expense 1 % 1 %
Acquisition and integration costs <1% <1%
Non-GAAP gross margin on net product sales Approximately 89% Approximately 89%

GAAP ETR 8 % 9 %
Income tax effect of GAAP to non-GAAP reconciling items 2 % 2 %
Non-GAAP ETR 10 % 11 %

(a) This press release uses non-GAAP R&D, non-GAAP SG&A, non-GAAP COGS, non-GAAP gross margin on net product sales, non-GAAP other operating (income) expense, net, non-GAAP other income (expense), net, non-GAAP ETR, non-GAAP net income, non-GAAP net income per share, total revenues excluding Ronapreve(b), and free cash flow, which are financial measures that are not calculated in accordance with U.S. Generally Accepted Accounting Principles (GAAP). These non-GAAP financial measures are computed by excluding certain non-cash and/or other items from the related GAAP financial measure. The Company also includes a non-GAAP adjustment for the estimated income tax effect of reconciling items. A reconciliation of the Company’s GAAP to non-GAAP results is included in Table 3 of this press release.

The Company makes such adjustments for items the Company does not view as useful in evaluating its operating performance. For example, adjustments may be made for items that fluctuate from period to period based on factors that are not within the Company’s control (such as the Company’s stock price on the dates share-based grants are issued or changes in the fair value of the Company’s investments in equity securities) or items that are not associated with normal, recurring operations (such as acquisition and integration costs). Management uses these non-GAAP measures for planning, budgeting, forecasting, assessing historical performance, and making financial and operational decisions, and also provides forecasts to investors on this basis. With respect to free cash flows, the Company believes that this non-GAAP measure provides a further measure of the Company’s ability to generate cash flows from its operations. Additionally, such non-GAAP measures provide investors with an enhanced understanding of the financial performance of the Company’s core business operations. However, there are limitations in the use of these and other non-GAAP financial measures as they exclude certain expenses that are recurring in nature. Furthermore, the Company’s non-GAAP financial measures may not be comparable with non-GAAP information provided by other companies. Any non-GAAP financial measure presented by the Company should be considered supplemental to, and not a substitute for, measures of financial performance prepared in accordance with GAAP.

(b) The casirivimab and imdevimab antibody cocktail for COVID-19 is known as REGEN-COV in the United States and Ronapreve in other countries. Roche records net product sales of Ronapreve outside the United States.

(c) The Company’s 2024 financial guidance does not assume the completion of any business development transactions not completed as of the date of this press release.

(d) Gross margin on net product sales represents gross profit expressed as a percentage of total net product sales recorded by the Company. Gross profit is calculated as net product sales less cost of goods sold.

(e) Corresponding reimbursements from collaborators and others for manufacturing of commercial supplies is recorded within revenues.

Conference Call Information

Regeneron will host a conference call and simultaneous webcast to discuss its third quarter 2024 financial and operating results on Thursday, October 31, 2024, at 8:30 AM Eastern Time. Participants may access the conference call live via webcast, or register in advance and participate via telephone, on the "Investors and Media" page of Regeneron’s website at www.regeneron.com. Upon registration, all telephone participants will receive a confirmation email detailing how to join the conference call, including the dial-in number along with a unique passcode and registrant ID that can be used to access the call. A replay of the conference call and webcast will be archived on the Company’s website for at least 30 days.

On October 31, 2024 NANOBIOTIX (Euronext: NANO –– NASDAQ: NBTX – the ‘‘Company’’), a late-clinical stage biotechnology company pioneering nanoparticle-based approaches to expand treatment possibilities for patients with cancer and other major diseases, reported that Company management will participate in fireside chats at following conferences (Press release, Nanobiotix, OCT 31, 2024, View Source [SID1234647607]):

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Guggenheim’s Inaugural Healthcare Innovation Conference
Date: Monday, November 11, 2024
Time: 4pm ET / 10pm CET
Location: Boston, MA
Presenters: Laurent Levy, Chief Executive Officer of Nanobiotix and Bart van Rhijn, Chief Financial & Business Officer of Nanobiotix
Webcast link: Click here

Stifel Healthcare Conference
Date: Monday, November 18, 2024
Time: 4:45pm ET / 10:45pm CET
Location: New York, NY
Presenter: Bart van Rhijn, Chief Financial & Business Officer of Nanobiotix
Webcast link: Click here

Jefferies London Healthcare Conference
Date: Wednesday, November 20, 2024
Time: 1pm GMT / 8am ET / 2pm CET
Location: London, UK
Presenters: Laurent Levy, Chief Executive Officer of Nanobiotix and Bart van Rhijn, Chief Financial & Business Officer of Nanobiotix
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The fireside chats will be webcast live from the events page of the Investors section of the Company’s website. Replay of the webcast will be available following the event.

On October 31, 2024 Molecular Partners AG (SIX: MOLN; NASDAQ: MOLN), a clinical-stage biotech company developing a new class of custom-built protein drugs known as DARPin therapeutics ("Molecular Partners" or the "Company"), reported corporate highlights and unaudited financial results for the third quarter of 2024 (Press release, Molecular Partners, OCT 31, 2024, View Source [SID1234647606]).

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"In the last quarter we continued to execute our plan to bring our first Radio-DARPin program to IND submission, and into the clinics. DLL3 remains a highly interesting target that is gaining significant attention. Our team presented additional preclinical data showing that MP0712 is safe and efficacious in a highly relevant tumor model, with DLL3 expression levels matching those in human tumors," said Patrick Amstutz, Ph.D., Molecular Partners’ Chief Executive Officer. "In addition, we strengthened our relationship with our partner Orano Med, ensuring that both parties will have the opportunity to bring two Radio-DARPin products to market, for a total of four. Lastly our recent capital raise allows us additional financial flexibility into 2027 with participation from new, specialized investors and supportive existing investors."

Financial and Business Outlook
For the full year 2024, at constant exchange rates, the Company reiterates its guidance for total expenses of CHF 65–70 million. Approximately CHF 7 million of this will be non-cash effective costs for share-based payments, pension accounting and depreciation. This guidance does not include any potential receipts from R&D collaborators.
With CHF 143.6 million in cash and short-term time deposits and no debt as of September 30, 2024, the Company expects to be funded into 2027, excluding any potential receipts from R&D collaborators.
On October 25, 2024, Molecular Partners announced the pricing of an underwritten offering in the US of 3’642’988 American Depositary Shares (ADSs) representing 3’642’988 ordinary shares at an offering price of USD 5.49 per ADS. The total gross proceeds amount to approximately USD 20 million. The offering included participation from a new investor HBM Healthcare Investments Ltd, which is a leading healthcare investor, as well as multiple existing investors. Leerink Partners and TD Cowen acted as joint bookrunning managers for the offering. LifeSci Capital acted as lead manager for the offering, and Zürcher Kantonalbank (ZKB) served as settlement agent. Molecular Partners currently intends to use the net proceeds from this offering, together with its existing cash and cash equivalents, for development and expansion of its radiopharmaceutical pipeline and platform (Radio-DARPin Therapeutics) and for working capital and other general corporate purposes. Subsequent to the offering, the Company has (proforma) cash and short-term time deposits in the amount of CHF 158 million, with 40,363,095 issued shares.

Research & Development Highlights

MP0712 and Radio-DARPin Therapy (RDT): Preparing for IND submission and clinical entry in 2025
Molecular Partners has leveraged the intrinsic properties of DARPins, such as small size, high affinity and specificity, to engineer Radio-DARPins as ideal vector candidates for radiopharmaceutical therapeutics and to create a Radio-DARPin Therapy (RDT) platform amenable to a broad range of tumor targets. Historically, small protein-based vectors faced challenges with kidney accumulation and toxicity, as well as suboptimal tumor uptake. Molecular Partners’ RDT platform addresses these limitations with its half-life extension technologies and surface engineering approaches, while preserving the advantages of the small protein format.

MP0712 is a 212Pb-based Radio-DARPin Therapeutic (RDT) candidate targeting the tumor-associated protein delta-like ligand 3 (DLL3). MP0712 is being co-developed with Orano Med, a clinical stage pioneer of targeted alpha therapies using the lead isotope 212Pb. Molecular Partners and Orano Med anticipate initiating first-in-human studies in 2025, pending regulatory clearance. Initial clinical data of MP0712 is also anticipated in 2025.

In October 2024, Molecular Partners presented new in vivo data at the EANM Congress. MP0712 demonstrated high affinity and specificity for DLL3 and a favorable safety profile. DLL3 is a highly relevant target for radiopharmaceutical therapy due to its abundant expression in tumors of patients with small cell lung cancer (present in >85% of tumors) and other aggressive neuroendocrine tumors, while expression in healthy tissues is low. MP0712 led to attractive tumor to kidney (T:K) ratios of >2 in biodistribution studies across several models, and to strong and dose-dependent efficacy in mice bearing established tumors with clinically-relevant levels of DLL3 expression and at a clinically-relevant dose.
On October 22, 2024, Molecular Partners and Orano Med signed a revised and strengthened agreement to co-develop 212Pb-based Radio-DARPin Therapeutics. This revision builds on the original agreement signed in January 2024. Under the revised agreement, both companies will co-develop four Radio-DARPin programs; each company will have the right to commercialize two programs (previously one each). Molecular Partners will hold commercialization rights to the second nominated Radio-DARPin candidate, in addition to rights to the first program MP0712.

In addition to the updates above, Molecular Partners continued to progress its RDT portfolio with projects through a partnership with Novartis, and is evaluating additional targets for RDT programs. An update on the broader RDT portfolio is expected to be shared in the first half of 2025.

MP0533 (multispecific T cell engager)

MP0533, a novel tetra-specific T cell-engaging DARPin, is currently being evaluated in a Phase 1/2a clinical trial for patients with relapsed/refractory acute myeloid leukemia (r/r AML) and myelodysplastic syndrome/AML (MDS/AML) (ClinicalTrials.gov: NCT05673057). The trial is currently enrolling patients in Cohort 8. MP0533’s mode of action is designed to preferentially kill AML cells (blasts, leukemic progenitor and stem cells) that express any combination of the three cell surface antigens CD33, CD123, and CD70, while sparing healthy cells, which tend to express only one or none of these targets. The immune activation against the malignant cells is achieved through CD3-mediated T-cell engagement.

As shared in August 2024, MP0533 showed an acceptable tolerability profile with the majority of adverse events reported being infusion-related reactions and cytokine release syndrome. Based on this observed tolerability profile and initial antitumor activity data, and following discussion with treating physicians and key opinion leaders, Molecular Partners is amending the protocol to further increase dosing and improve the exposure profile of MP0533.
Molecular Partners plans to present the next clinical update of the program at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in San Diego on December 7–10, 2024, and data following the protocol amendment are expected in 2025.

Switch-DARPin Platform (next-gen immune cell engagers)
The Switch-DARPin platform provides a logic-gated "on/off" function (the "Switch") to multi-specific DARPin candidates leading to target activation only in the presence of defined antigens. The objective is conditional activation of a targeted immune response.

MP0621 is a Switch-DARPin candidate designed to induce killing of hematopoietic stem cells as a next-generation conditioning regimen for HSCT. The in vivo proof-of-mechanism data, as presented at EHA (Free EHA Whitepaper) 2024, demonstrate that MP0621 could be an efficient next-generation conditioning regimen for autologous HSCT. At present, the non-human primate data do not indicate that MP0621 would serve as a treatment for AML. As Molecular Partners’ portfolio strategy prioritizes therapeutic candidates for oncology, MP0621 is being evaluated for partnering. The Company plans to present a preclinical update on MP0621 at ASH (Free ASH Whitepaper) 2024.

Proof-of-concept preclinical data on an additional Switch-DARPin candidate, namely a CD3 Switch-DARPin T cell engager for solid tumors, will be presented at SITC (Free SITC Whitepaper) 2024 on November 9, 2024. The CD3 Switch-DARPin targets the highly validated immunostimulatory protein CD3 to deliver a T cell-engager (TCE) mechanism with enhanced function via engagement of additional receptors on the surface of T cells. TCEs are a powerful class of immuno-oncology therapies but have faced a range of challenges such as toxicity, poor T cell fitness and immune suppression, particularly in solid tumors. By employing a multi-specific Switch approach, Molecular Partners aims to broaden the therapeutic space for T cell engagers.

MP0317 (localized agonist)

MP0317 is a CD40 agonist designed to activate immune cells specifically within the tumor microenvironment (TME) by anchoring to fibroblast activation protein (FAP) which is expressed in high amounts around tumors. This tumor-localized approach has the potential to deliver greater efficacy with fewer side effects compared to systemic CD40-targeting therapies.

In September 2024, the Company presented details of the transcriptomic analysis from its completed Phase 1 study at CICON 2024. The analysis of patient biopsies pre- and post-treatment with MP0317 showed that this molecule remodels the tumor microenvironment by inducing infiltration of B, plasma, dendritic, and T follicular helper cells.
Molecular Partners plans to share a comprehensive biomarker analysis of its completed Phase 1 study at SITC (Free SITC Whitepaper) on November 9, 2024.

The positive Phase 1 data support further clinical evaluation of MP0317 in combination with complementary anticancer therapies and demonstrated the ability of the DARPin design to deliver on a targeted, tumor-localized CD40 activation mechanism. Molecular Partners is in discussion with leading academic centers regarding potential investigator-initiated combination trials.