On November 6, 2024 Enterome, a clinical-stage company developing first-in-class immunomodulatory drugs for cancer based on its unique Mimicry platform, reported that clinical data from the ongoing Phase 1/2 ‘SIDNEY’ trial of EO2463, an experimental treatment for indolent non-Hodgkin B-cell lymphoma (iNHL), will be presented at the 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Conference, to take place December 7-10, 2024, in San Diego, California, and online (Press release, Enterome, NOV 6, 2024, View Source [SID1234647810]).

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These presentations will disclose the first data from Phase 2 Cohort 2, evaluating EO2463 as monotherapy for newly diagnosed patients with asymptomatic follicular lymphoma, where EO2463 may offer a safe, proactive immune therapy alternative to the usual "watch-and-wait" observation strategy. The data also report initial findings on a biomarker with potential to predict long-term response to EO2463, both as monotherapy, and in combination with standard treatments, in relapsed/refractory iNHL.

Details of the poster presentations:

Abstract #1616

Title: EO2463 Peptide Immunotherapy in Patients with Indolent NHL: A Phase 1 Exploration of a Response Biomarker for EO2463 Monotherapy and EO2463 in Combination with Lenalidomide/Rituximab
Presenting Author: J.C. C. Villasboas Bisneto, M.D., Mayo Clinic
Session: 622. Lymphomas: Translational – Non-Genetic: Poster I
Session Date: Saturday, December 7, 2024
Presentation Time: 5:30 PM – 7:30 PM
Abstract #4395

Title: EO2463 Peptide Immunotherapy in Patients with Newly Diagnosed Asymptomatic Follicular Lymphoma Results in Monotherapy Objective Clinical Responses Linked with Anti-Peptide Specific CD8 Memory T Cell Responses: The EONHL1-20/SIDNEY Study
Presenting Author: Stephen Smith, M.D., Associate Professor, UW Medicine & Fred Hutchinson Cancer Center
Session: 623. Mantle Cell, Follicular, Waldenstrom’s, and Other Indolent B Cell Lymphomas: Clinical and Epidemiological: Poster III
Session Date: Monday, December 9, 2024
Presentation Time: 6:00 PM – 8:00 PM
SIDNEY (EONHL1-20) is a Phase 1/2 multicenter, open-label, first-in-human study of EO2463 as a monotherapy and in combination with lenalidomide and/or rituximab for the treatment of patients with iNHL. The study aims to assess the safety, tolerability, immunogenicity, and preliminary efficacy of EO2463 monotherapy and combination therapy in approximately 60 patients with follicular lymphoma (FL) and marginal zone lymphoma (MZL).

For more information on the study, visit www.Clinicaltrials.gov, reference: NCT04669171.

About EO2463:

EO2463 is an innovative, off-the-shelf immunotherapy candidate that combines four synthetic OncoMimic peptides. These non-self, microbial-derived peptides correspond to CD8 HLA-A2 epitopes that exhibit molecular mimicry with the B lymphocyte-specific lineage markers CD20, CD22, CD37, and CD268 (BAFF receptor). EO2463 also includes the helper peptide (CD4+ epitope) universal cancer peptide 2 (UCP2).

The unique ability of EO2463 immunotherapy to selectively target multiple B cell markers enables the destruction of malignant B lymphocytes that are abundant in iNHL. By ensuring broad target coverage across malignant B cells, this novel approach aims to simultaneously improve safety and maximize efficacy, reducing the tumor cells’ capacity to develop immune-resistance mechanisms.

On November 6, 2024 Elevation Oncology, Inc. (Nasdaq: ELEV), an innovative oncology company focused on the discovery and development of selective cancer therapies to treat patients across a range of solid tumors with significant unmet medical needs, reported financial results for the third quarter ended September 30, 2024, and highlighted recent business achievements (Press release, Elevation Oncology, NOV 6, 2024, View Source;utm_medium=rss&utm_campaign=elevation-oncology-reports-third-quarter-2024-financial-results-and-highlights-recent-business-achievements [SID1234647809]).

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"We continue to make significant progress with EO-3021, our potentially best-in-class Claudin 18.2 antibody-drug conjugate (ADC). Based on the favorable initial clinical data reported in August, we are advancing EO-3021 in both the monotherapy and combination settings across early and later lines of therapy for patients with Claudin 18.2-expressing gastric or GEJ cancer," said Joseph Ferra, President and Chief Executive Officer of Elevation Oncology. "In the past quarter, we initiated the dose expansion portion of the Phase 1 trial of monotherapy EO-3021 and we look forward to reporting additional data in the first half of 2025."

Mr. Ferra continued, "We are encouraged by the promising preliminary efficacy and differentiated safety profile seen in the dose escalation portion of our Phase 1 trial. The favorable initial data highlights EO-3021’s unique potential as a more combinable Claudin 18.2 ADC with competitive anti-tumor activity. We are well-positioned to explore the full promise of EO-3021 including its better combinability, and are initiating the combination portion of our Phase 1 trial in Q4 2024. Additionally, we look forward to sharing preclinical data at ESMO (Free ESMO Whitepaper)-IO 2024 in December that further reinforce our combination strategy with VEGFR2 or PD-1 inhibitors. Together with our ongoing monotherapy efforts, this reflects a robust, broad clinical development plan that will allow us to evaluate EO-3021 across the first, second and later lines of therapy. We remain focused on generating meaningful data and executing toward our goal of bringing important treatment options to patients with significant unmet medical needs."

Recent Business Achievements

In September 2024, Elevation Oncology announced that the U.S. Food and Drug Administration (FDA) granted Fast Track designation (FTD) to EO-3021 for the treatment of patients with advanced or metastatic gastric and gastroesophageal junction (GC/GEJ) cancer expressing Claudin 18.2 that has progressed on or after prior therapy. Fast Track is a process designed by the FDA to facilitate the development and expedite the review of therapeutic candidates intended to treat serious or life-threatening conditions, for which nonclinical or clinical data demonstrate the potential to address unmet medical needs. Therapeutic candidates that receive FTD may be eligible for more frequent interactions with the FDA to discuss the candidate’s development plan. Therapeutic candidates with FTD may also be eligible for priority review and accelerated approval if supported by clinical data.
In August 2024, Elevation Oncology announced promising initial clinical data from the dose escalation portion of the ongoing Phase 1 clinical trial of EO-3021 in patients with advanced, unresectable or metastatic solid tumors likely to express Claudin 18.2, including gastric, GEJ, pancreatic or esophageal cancers. As of the data cutoff date of June 10, 2024:
In seven patients with Claudin 18.2 in ≥20% of tumor cells at IHC 2+/3+:
Objective response rate (ORR) was 42.8% (three confirmed partial responses, one of which was confirmed following the June 10, 2024 data cutoff).
Disease control rate (DCR) was 71.4%, including two patients with stable disease.
EO-3021 was observed to be generally well-tolerated:
Minimal hematological toxicity or hepatotoxicity, and no peripheral neuropathy/hypoesthesia was observed in the safety population of 32 patients treated with EO-3021.
Initial safety data suggests minimal payload-associated toxicity and limited overlapping toxicity with standard-of-care agents including PD-1 inhibitors and chemotherapies.
Expected Upcoming Milestones

EO-3021:

Present preclinical data on the combination potential of EO-3021 with VEGFR2 or PD-1 inhibitors at ESMO (Free ESMO Whitepaper)-IO 2024 in December 2024.
Initiate dosing in combination portion of the ongoing Phase 1 clinical trial of EO-3021 in the fourth quarter of 2024; combination cohorts will explore EO-3021 in combination with ramucirumab, a VEGFR2 inhibitor, in the second-line setting and in combination with dostarlimab, a PD-1 inhibitor, in the front-line setting.
Report additional data from the ongoing Phase 1 clinical trial of monotherapy EO-3021, including from the dose expansion cohort, in the first half of 2025.
HER3-ADC:

Nominate development candidate for HER3-ADC program in the fourth quarter of 2024.
Third Quarter 2024 Financial Results

As of September 30, 2024, Elevation Oncology had cash, cash equivalents and marketable securities totaling $103.1 million, compared to $83.1 million as of December 31, 2023. The increase in cash reflects net proceeds of $44.2 million, which Elevation Oncology raised through its at-the-market (ATM) facility in the first half of 2024, partially offset by cash used to fund operating activities.

Research and development (R&D) expenses for the third quarter of 2024 were $9.4 million, compared to $7.4 million for the third quarter of 2023. The increase in R&D expenses was driven by continuous investment in the Company’s lead and pipeline programs.

General and administrative (G&A) expenses for the third quarter of 2024 were $3.8 million, compared to $3.5 million for the third quarter of 2023. The increase in G&A expenses in the third quarter of 2024 was primarily due to increased personnel costs, including stock-based compensation.

Net loss for the third quarter of 2024 was $12.9 million, compared to $10.6 million for the third quarter of 2023.

Financial Outlook

Elevation Oncology expects its existing cash, cash equivalents and marketable securities as of September 30, 2024 to be sufficient to fund its current operations into 2026.

About EO-3021

EO-3021 is a differentiated, clinical-stage, potentially best-in-class, antibody-drug conjugate (ADC) comprised of an immunoglobulin G1 (IgG1) monoclonal antibody (mAb) that targets Claudin 18.2 and a monomethyl auristatin E (MMAE) payload with a cleavable linker that is site-specifically conjugated to Glutamine 295 providing a drug-to-antibody ratio (DAR) of 2. Claudin 18.2 is a specific isoform of Claudin 18 that is normally expressed in gastric epithelial cells. During malignant transformation, the tight junctions may become disrupted, exposing Claudin 18.2 and allowing them to be accessible by Claudin 18.2 targeting agents. Elevation Oncology is evaluating EO-3021 in the dose expansion portion of a Phase 1 trial (NCT05980416) in patients with advanced, unresectable or metastatic gastric/gastroesophageal adenocarcinoma that express Claudin 18.2. Following recently signed clinical supply agreements with Lilly and GSK, respectively, Elevation Oncology will evaluate EO-3021 in combination with ramucirumab, a VEGFR2 inhibitor, in second-line patients and in combination with dostarlimab, a PD-1 inhibitor, in the front-line setting.

In September 2024, EO-3021 was granted Fast Track designation by the FDA for the treatment of patients with advanced or metastatic gastric and gastroesophageal junction (GC/GEJ) cancer expressing Claudin 18.2 that has progressed on or after prior therapy. EO-3021 was granted orphan drug designation by the FDA for the treatment of gastric cancer (including cancer of gastroesophageal junction) in November 2020 and for the treatment of pancreatic cancer in May 2021.

Elevation Oncology has the exclusive rights to develop and commercialize EO-3021 in all global territories outside Greater China.

On November 6, 2024 Coherus BioSciences, Inc. (Coherus or the Company, Nasdaq: CHRS), reported financial results for the quarter ended September 30, 2024 and recent business highlights (Press release, Coherus Biosciences, NOV 6, 2024, View Source [SID1234647808]):

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"Revenue growth was strong in the third quarter, with the UDENYCA franchise increasing 30% compared to the second quarter, and 100% over Q3 2023. LOQTORZI sales grew more than 50% compared to the second quarter of 2024," said Denny Lanfear, Coherus Chairman and Chief Executive Officer. "Our sharpened focus on oncology is delivering results. Third quarter 2024 revenues are now comparable to Q3 2023, despite our divestitures, with higher gross profit, lower operating expenses and lower interest expense."

"We continue to make progress towards our long-term vision of bringing innovative, next-generation therapies to extend cancer patient survival. Our competitively positioned pipeline, in combination with LOQTORZI, is advancing to plan in tumor types with high unmet medical need and with robust supportive biology," continued Mr. Lanfear.

RECENT BUSINESS HIGHLIGHTS

UDENYCA RESULTS

● UDENYCA net product sales were $66.1 million in Q3 2024, an increase of 30% compared to $50.9 million in Q2 2024 and a 100% increase compared to $33.0 million in Q3 2023.
● Q3 revenue was driven by a 54% increase in demand for ONBODY and a higher overall net selling price.
● In Q3, UDENYCA maintained its #2 position in the pegfilgrastim class with 28% market share.

UDENYCA SUPPLY UPDATE

● Coherus’ third-party labeling and packaging contract manufacturing organization (CMO) for UDENYCA has informed the Company that production will resume this week, a few weeks later than previously targeted and disclosed. Based on the production schedule, the backlog of UDENYCA lots of approximately 120,000 units will be completed without further interruption or delay by the end of the year.
● The Company has also made significant progress in its previously announced efforts to diversify its labeling and packaging resources. An additional final packaging and labeling CMO has already started production testing and is expected to start manufacturing saleable product by the end of 2024. Commercial supply from that CMO is expected to commence in the first quarter of 2025, subject to U.S. Food and Drug Administration (FDA) authorization. Once the second facility is commercially operational, the Company projects that its labeling and packaging capacity will have doubled to over one million UDENYCA units annually, consistent with the rest of its supply chain.

LOQTORZI LAUNCH UPDATE

● LOQTORZI, the first and only FDA-approved treatment for recurrent, locally advanced or metastatic nasopharyngeal carcinoma (NPC), commercially launched across all lines of therapy on January 2, 2024.
1

● LOQTORZI net product sales were $5.8 million in Q3 2024, an increase of 54% compared to $3.8 million in Q2 2024.
● The number of LOQTORZI treated patients grew by more than 60% in Q3, with new patient uptake primarily in relapsed locally advanced and 1L metastatic disease, the key driver of long-term revenue growth.
● Since launch, nearly 80% of all National Comprehensive Cancer Network (NCCN) institutions have written prescriptions for at least one new patient.

ADVANCEMENT OF PROMISING IMMUNO-ONCOLOGY PIPELINE

● This quarter, the Company expects to open a Phase 2 randomized study evaluating casdozokitug, an immune regulatory IL-27 antagonist in combination with toripalimab and bevacizumab for the treatment of unresectable locally advanced or metastatic hepatocellular carcinoma (HCC) in treatment-naive patients.
● The Company also anticipates final data from its Phase 2 trial of casdozokitug combined with atezolizumab and bevacizumab in first-line HCC in the first quarter of 2025. Coherus has received FDA orphan drug status and fast track designation for casdozokitug in HCC.
● A Phase 1 study evaluating CHS-114, a highly selective cytolytic anti-CCR8 antibody, is ongoing. In the first half of 2025, Coherus expects to report Phase 1 data from expansion cohorts evaluating CHS-114 as monotherapy and in combination with toripalimab in patients with advanced/metastatic head and neck squamous cell carcinoma (HNSCC).
● Coherus plans to initiate Phase 1b dose optimization studies of CHS-114 in combination with toripalimab in patients with HNSCC and gastric cancer in the first quarter of 2025, with initial data for both studies expected in the first half of 2026.

THIRD QUARTER 2024 FINANCIAL RESULTS

Net revenue was $70.8 million during the three months ended September 30, 2024, and included $66.1 million of net sales of UDENYCA and $5.8 million of net sales of LOQTORZI. Net revenue was $74.6 million during the three months ended September 30, 2023 and included $33.0 million in net sales of UDENYCA and $41.4 million attributable to the Company’s divested products, CIMERLI and YUSIMRY.

Net revenue was $212.8 million and $165.7 million for the nine months ended September 30, 2024 and 2023, respectively. Total net revenue attributable to the Company’s divested products, CIMERLI and YUSIMRY, during the first nine months of 2024 and 2023 was $34.5 million and $74.3 million, respectively. In addition, the first nine months of 2024 included other revenue of $7.0 million mainly comprising the $6.3 million up-front cash payment received for the outlicense to Apotex, Inc. of the Canadian rights to LOQTORZI on June 27, 2024.

Cost of goods sold (COGS) was $20.7 million and $32.7 million during the three months ended September 30, 2024 and 2023, respectively, and $83.7 million and $74.4 million during the nine months ended September 30, 2024 and 2023, respectively. The decrease in COGS for the third quarter of 2024 compared to the same period in the prior year was primarily due to $24.1 million of COGS in the third quarter of 2023 related to CIMERLI and YUSIMRY, which were divested during the first half of 2024, partially offset by a $9.7 million increase in product costs driven by increased UDENYCA volume.

The increase in COGS for the nine months ended September 30, 2024 compared to the same period in the prior year was primarily due to a $27.8 million increase related to volumes driven by UDENYCA and LOQTORZI, $4.5 million in connection with a CMO contract change, and $2.5 million in LOQTORZI royalties. These increases were partially offset by non-recurring COGS related to products divested during the first half of 2024 mentioned above.

Research and development (R&D) expenses were $21.7 million and $25.6 million for the three months ended September 30, 2024 and 2023, respectively, and $72.1 million and $83.1 million for the nine months ended September 30, 2024 and 2023, respectively. The decreases were primarily due to savings from reduced headcount and lower costs related to biosimilar product divestitures, partially offset by costs for development of casdozokitug and CHS-114.

Selling, general and administrative (SG&A) expenses were $34.7 million and $48.2 million during the three months ended September 30, 2024 and 2023, respectively, and $126.4 million and $142.5 million during the nine months ended September 30, 2024 and 2023, respectively. The declines in SG&A compared to the prior year periods were driven primarily by lower headcount. The decrease for the nine-month period was partially offset by the net $6.8 million charge in the first quarter of 2024 associated with the full write-off of the outlicense intangible asset and associated release of the CVR liability related to NZV930, obtained in the Surface Oncology, Inc. acquisition.

Interest expense was $5.4 million and $10.3 million during the three months ended September 30, 2024 and 2023, respectively, and $21.8 million and $29.9 million during the nine months ended September 30, 2024 and 2023, respectively. The declines in both periods were primarily due to prepaying $175.0 million of the principal amount due under the 2027 Term Loans on April 1, 2024 and the remaining $75.0 million principal amount on May 8, 2024, partially offset by interest on the senior secured term loan facility of up to $38.7 million and the revenue participation right purchase and sale agreement, both commencing May 8, 2024.

Gain on sale transactions, net was $176.6 million for the nine months ended September 30, 2024 and included a $153.8 million gain on the divestiture of our CIMERLI ophthalmology franchise, which closed during the first quarter of 2024, and a $22.9 million gain on the divestiture of our YUSIMRY immunology franchise, which closed during the second quarter of 2024. There was no gain on sale transactions in the nine months ended September 30, 2023.

Net loss for the third quarter of 2024 was $10.8 million, or $(0.09) per share on a diluted basis, compared to a net loss of $39.6 million, or $(0.41) per share on a diluted basis for the same period in 2023. Net income for the nine months ended September 30, 2024 was $79.2 million, or $0.65 per share on a diluted basis, compared to a net loss of $158.2 million, or $(1.79) per share on a diluted basis for nine months ended September 30, 2023.

On November 6, 2024 Charles River Laboratories International, Inc. (NYSE: CRL) reported its results for the third quarter of 2024. For the quarter, revenue was $1.01 billion, a decrease of 1.6% from $1.03 billion in the third quarter of 2023 (Press release, Charles River Laboratories, NOV 6, 2024, View Source [SID1234647807]).

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The impact of foreign currency translation benefited reported revenue by 0.4%, and an acquisition contributed 0.9% to consolidated third-quarter revenue. A divestiture of a small Safety Assessment site reduced reported revenue by 0.2%. Excluding the effect of these items, revenue declined 2.7% on an organic basis. On a segment basis, organic revenue growth in the Manufacturing Solutions (Manufacturing) and Research Models and Services (RMS) segments were more than offset by lower revenue in the Discovery and Safety Assessment (DSA) segment.
In the third quarter of 2024, the GAAP operating margin decreased to 11.6% from 14.8% in the third quarter of 2023. This GAAP decrease was primarily driven by costs associated with the Company’s restructuring initiatives. On a non-GAAP basis, the operating margin improved in all three segments; however, the improvements were more than offset by higher unallocated corporate costs, which resulted in the third-quarter operating margin decreasing to 19.9% from 20.5%.

On a GAAP basis, third-quarter net income attributable to common shareholders was $68.7 million, a decrease of 21.4% from $87.4 million for the same period in 2023. Third-quarter diluted earnings per share on a GAAP basis were $1.33, a decrease of 21.3% from $1.69 for the third quarter of 2023. The GAAP net income and earnings per share decreases were driven primarily by lower revenue and operating income, which included higher costs associated with the Company’s restructuring initiatives. On a non-GAAP basis, net income was $133.7 million for the third quarter of 2024, a decrease of 4.8% from $140.5 million for the same period in 2023. Third-quarter diluted earnings per share on a non-GAAP basis were $2.59, a decrease of 4.8% from $2.72 per share for the third quarter of 2023. The decreases in non-GAAP net income and earnings per share were driven primarily by lower revenue and operating income.

James C. Foster, Chair, President and Chief Executive Officer, said, "Forward-looking demand indicators were relatively stable in the third quarter, contributing to third-quarter financial performance which exceeded our prior outlook. We are continuing to navigate through a challenging period as global biopharmaceutical clients reduce spending in conjunction with major restructuring and pipeline reprioritization activities, but overall demand trends do not appear to have deteriorated further. In addition, biotech funding has improved in 2024, and demand appears to be demonstrating early signs of stabilization. These factors resulted in a slight, sequential improvement in net book-to-bill and the cancellation rate in the Safety Assessment business."

"We remain laser focused during this period on our strategy, which includes aggressively managing our cost structure, enhancing our clients’ experiences to gain additional share, and protecting shareholder value. We will continue to distinguish ourselves through our exceptional science and preclinical focus, in order to extend our leading position as our clients’ preferred, global, non-clinical drug development partner. We expect to emerge from this period as a stronger, leaner, and more profitable company, and an even more responsive partner for our clients," Mr. Foster concluded.
Third-Quarter Segment Results

Research Models and Services (RMS)

Revenue for the RMS segment was $197.8 million in the third quarter of 2024, an increase of 5.9% from $186.8 million in the third quarter of 2023. The Noveprim acquisition in November 2023 contributed 4.9% to third-quarter RMS reported revenue, and the impact of foreign currency translation increased revenue by 0.4%. Organic revenue increased by 0.6%, due primarily to higher sales of small research models in all geographic regions, principally driven by higher pricing. This was largely offset by a revenue decline for research model services, particularly in the Insourcing Solutions business.

In the third quarter of 2024, the RMS segment’s GAAP operating margin decreased to 13.9% from 15.2% in the third quarter of 2023. The GAAP operating margin decline was driven primarily by higher amortization expense related to the Noveprim acquisition coupled with higher costs associated with the Company’s restructuring initiatives, including severance and site consolidation costs. On a non-GAAP basis, the operating margin increased to 21.0% from 18.9%. The non-GAAP operating margin increase was primarily driven by higher pricing for small research models, a favorable revenue mix related to the Noveprim acquisition, and the benefit of cost savings associated with the Company’s restructuring initiatives.

Discovery and Safety Assessment (DSA)

Revenue for the DSA segment was $615.1 million in the third quarter of 2024, a decrease of 7.4% from $664.0 million in the third quarter of 2023. The divestiture of a small Safety Assessment site reduced reported revenue by 0.3% and the impact of foreign currency translation increased DSA revenue by 0.3%. Organic revenue decreased by 7.4%, driven primarily by lower sales volume in both the Discovery Services and Safety Assessment businesses.

In the third quarter of 2024, the DSA segment’s GAAP operating margin decreased to 20.6% from 22.1% in the third quarter of 2023 primarily driven by lower revenue and higher severance costs related to restructuring initiatives. On a non-GAAP basis, the operating margin increased to 27.4% from 27.2% in the third quarter of 2023. The non-GAAP operating margin increase was primarily driven by the benefit of cost savings associated with restructuring initiatives.
Manufacturing Solutions (Manufacturing)
Revenue for the Manufacturing segment was $196.9 million in the third quarter of 2024, an increase of 12.0% from $175.7 million in the third quarter of 2023. The impact of foreign currency translation increased Manufacturing revenue by 0.2%. Organic revenue growth of 11.8% reflected higher revenue across each of the segment’s businesses.
In the third quarter of 2024, the Manufacturing segment’s GAAP operating margin increased to 20.4% from 15.0% in the third quarter of 2023, and on a non-GAAP basis, the operating margin increased to 28.7%, from 24.5% in the third quarter of 2023. The GAAP and non-GAAP operating margin increases were driven primarily by improved operating leverage from higher revenue in each of segment’s businesses, as well as the benefit of cost savings associated with restructuring initiatives.
Stock Repurchase Update
On August 2, 2024, the Company’s Board of Directors approved a new stock repurchase authorization of $1.0 billion. Following the new authorization, the Company repurchased 500,000 shares during the third quarter of 2024 for a total of $100.7 million. As of September 28, 2024, the Company has $899.3 million remaining on its $1.0 billion stock repurchase authorization.
Updates 2024 Guidance
The Company is updating its financial guidance for 2024, which was previously revised on August 7, 2024. Revenue and non-GAAP earnings per share guidance have been narrowed and slightly raised from the midpoint of the previous ranges to principally reflect the third-quarter financial performance, which exceeded the Company’s prior outlook. In addition, GAAP earnings per share guidance has been reduced due primarily to increased charges related to the Company’s additional restructuring actions.

On November 6, 2024 Celldex Therapeutics, Inc. (NASDAQ:CLDX) reported financial results for the third quarter ended September 30, 2024 and provided a corporate update (Press release, Celldex Therapeutics, NOV 6, 2024, View Source [SID1234647805]).

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"Celldex recently presented best-in-disease data across both our Phase 2 studies of barzolvolimab in CSU and CIndU," said Anthony Marucci, Co-founder, President and Chief Executive Officer of Celldex Therapeutics. "The data demonstrated barzolvolimab’s unique potential to provide a rapid, durable treatment option and complete disease control for patients suffering from these severe, debilitating diseases. These are transformative results for patients with CSU, many whom do not see meaningful benefit from the current standard of care, and CIndU, where there are currently no approved therapies other than antihistamines. We continue to make strong progress across our entire pipeline, with enrollment ongoing in global Phase 3 CSU trials and our Phase 2 PN and EOE studies. As we look to the end of this year, we remain excited for our Phase 2 study in AD to initiate and our first bispecific for inflammatory diseases, CDX-622, to enter the clinic."

Recent Program Highlights

Barzolvolimab – KIT Inhibitor Program

Barzolvolimab is a humanized monoclonal antibody developed by Celldex that binds the KIT receptor with high specificity and potently inhibits its activity. The KIT receptor tyrosine kinase is expressed in a variety of cells, including mast cells, which mediate inflammatory responses such as hypersensitivity and allergic reactions. KIT signaling controls the differentiation, tissue recruitment, survival and activity of mast cells.

Chronic Urticarias

Phase 3 Development

A global Phase 3 program in chronic spontaneous urticaria (CSU) was initiated in July, consisting of two Phase 3 trials (EMBARQ-CSU1 and EMBARQ-CSU2) designed to establish the efficacy and safety of barzolvolimab in adult patients with CSU who remain symptomatic despite H1 antihistamine treatment. The studies also include patients who remain symptomatic after treatment with biologics. The studies will enroll approximately 915 patients each across 40 countries and 500 sites and are actively enrolling patients.
The Company is currently planning a global Phase 3 program in chronic inducible urticaria (CIndU), which is expected to initiate in 2025.
Phase 2 Development

Barzolvolimab met all primary and secondary endpoints at 12 weeks across the Company’s Phase 2 studies in CSU and CIndU. Results were highly statistically significant and clinically meaningful. Patients continue to be followed on both studies.

52 week long term follow up data from the Phase 2 study in CSU (n=208) were presented in a late breaking oral presentation at the EADV Congress 2024 in September. A deepening of response was observed over the 52 week treatment period and barzolvolimab demonstrated the highest rate of complete response observed in a well controlled study in CSU with 71% of patients (150 mg Q4W) achieving a complete response at Week 52. Importantly, barzolvolimab was also well tolerated through 52 weeks.

12 week primary endpoint data from the Phase 2 study in CIndU (n=196) were presented in a late breaking oral presentation at ACAAI 2024 in October. Barzolvolimab is the first drug to demonstrate clinical benefit in patients with cold urticaria (ColdU) in a large, randomized, placebo-controlled study. Per provocation test, up to 53.1% of patients with ColdU and 57.6% of patients with symptomatic dermographism (SD) treated with barzolvolimab experienced a complete response compared to placebo rates of only 12.5% (p=0.0011) in ColdU and 3.2% (p<0.0001) in SD—the primary endpoint of the study. Secondary and exploratory endpoints were highly supportive of the primary endpoint. Patients on study continued to receive barzolvolimab or placebo for up 20 weeks and are being followed for an additional 24 weeks. The study also includes an Open Label Extension that allows patients with symptoms during the follow-up phase (including patients who were on placebo) to receive active study drug.
Additional Indications

A Phase 2 study in eosinophilic esophagitis (EoE) was initiated in July 2023 and enrollment is ongoing. This randomized, double-blind, placebo-controlled study is evaluating the efficacy and safety profile of barzolvolimab in approximately 75 patients with active EoE. Data from this study is expected in the second half of 2025.
A Phase 2 study in prurigo nodularis (PN) was initiated in early 2024 and enrollment is ongoing. This randomized, double-blind, placebo-controlled, parallel group study is evaluating the efficacy and safety profile of barzolvolimab in approximately 120 patients with moderate to severe PN who had inadequate response to prescription topical medications, or for whom topical medications are medically inadvisable, including patients who received prior biologics.
In May 2024, Celldex announced that atopic dermatitis (AD) has been selected as the fifth indication for the development of barzolvolimab. Barzolvolimab’s novel mast cell depleting mechanism could play an important role in addressing patients with moderate to severe AD who do not achieve complete disease control on currently available systemic therapies. Celldex plans to initiate a Phase 2 study in AD by year end.
Bispecific Antibody Platform

CDX-622 – Bispecific SCF & TSLP

CDX-622 targets two complementary pathways that drive chronic inflammation, potently neutralizing the alarmin thymic stromal lymphopoietin (TSLP) and depleting mast cells via stem cell factor (SCF) starvation. Combined neutralization of SCF and TSLP with CDX-622 is expected to simultaneously reduce tissue mast cells and inhibit Type 2 inflammatory responses to potentially offer enhanced therapeutic benefit in inflammatory and fibrotic disorders.

Celldex has completed preclinical, manufacturing and IND-enabling activities for CDX-622 and plans to initiate a Phase 1 study in healthy volunteers by the end of 2024. In preclinical studies, CDX-622 inhibits TSLP and SCF with similar potency to both its respective parental mAbs and comparator mAbs in vitro. CDX-622 was well tolerated in a multi-dose 8 week toxicology study in non-human primates and the No Adverse Event Level (NOAEL) was established to be 75 mg/kg, the highest dose level tested. In inflammatory and fibrotic disorders, TSLP is often upregulated and associated with disease severity. Similarly, mast cells drive or contribute to the pathophysiology of many of these disorders and CDX-622 contains a unique SCF neutralizing function that is expected to inhibit and deplete mast cells.
CDX-585 – Bispecific ILT4 & PD-1

The dose-escalation portion of this open-label, multi-center Phase 1 study of CDX-585 in patients with advanced or metastatic solid tumors that have progressed during or after standard of care therapy has been completed. We are prioritizing our expanding clinical development program in the inflammatory space and will not advance CDX-585.
Third Quarter 2024 Financial Highlights and 2024 Guidance

Cash Position: Cash, cash equivalents and marketable securities as of September 30, 2024 were $756.0 million compared to $802.3 million as of June 30, 2024. The decrease was primarily driven by third quarter cash used in operating activities of $55.3 million. From June 30, 2024 to September 30, 2024, prepaid and other current assets increased $13.9 million and other assets increased $9.6 million as a result of non-recurring advance payments related to our Phase 3 studies in CSU and late-stage barzolvolimab commercial manufacturing batches. At September 30, 2024, Celldex had 66.3 million shares outstanding.

Revenues: Total revenue was $3.2 million in the third quarter of 2024 and $5.8 million for the nine months ended September 30, 2024, compared to $1.5 million and $2.8 million for the comparable periods in 2023. The increase in revenue was primarily due to an increase in services performed under our manufacturing and research and development agreements with Rockefeller University.

R&D Expenses: Research and development (R&D) expenses were $45.3 million in the third quarter of 2024 and $116.6 million for the nine months ended September 30, 2024, compared to $34.5 million and $87.6 million for the comparable periods in 2023. The increase in R&D expenses was primarily due to an increase in barzolvolimab clinical trial and personnel expenses, partially offset by a decrease in barzolvolimab contract manufacturing expenses.

G&A Expenses: General and administrative (G&A) expenses were $10.1 million in the third quarter of 2024 and $28.3 million for the nine months ended September 30, 2024, compared to $8.2 million and $22.1 million for the comparable periods in 2023. The increase in G&A expenses was primarily due to an increase in stock-based compensation and barzolvolimab commercial planning expenses.

Net Loss: Net loss was $42.1 million, or ($0.64) per share, for the third quarter of 2024, and $110.8 million, or ($1.74) per share, for the nine months ended September 30, 2024, compared to a net loss of $38.3 million, or ($0.81) per share, for the third quarter of 2023, and $98.1 million, or ($2.08) per share, for the nine months ended September 30, 2023.

Financial Guidance: Celldex believes that the cash, cash equivalents and marketable securities at September 30, 2024 are sufficient to meet estimated working capital requirements and fund current planned operations through 2027.