On October 29, 2024 Incyte (Nasdaq:INCY) reported 2024 third quarter financial results, and provides a status update on the Company’s clinical development portfolio (Press release, Incyte, OCT 29, 2024, View Source [SID1234647483]).

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"In the third quarter of 2024, we delivered significant achievements, including strong revenue growth for both Jakafi (ruxolitinib) and Opzelura (ruxolitinib) cream, and the advancement of our clinical pipeline highlighted by the submission to the FDA of the supplemental New Drug Application (sNDA) for ruxolitinib cream in pediatric atopic dermatitis and several key data readouts including CDK2i, retifanlimab, tafasitamab, povorcitinib and ruxolitinib cream, which all hold near to mid-term launch potential. Additionally, in August, the FDA approved Niktimvo (axatilimab-csfr) for patients with chronic graft-versus-host disease, after failure of two prior lines of therapy, making it the first anti-CSF-1R antibody approved to target the inflammation and fibrosis associated with chronic GVHD," said Hervé Hoppenot, Chief Executive Officer, Incyte. "We are on track to achieve over ten impactful launches by 2030."

Key Recent Company Updates

•In October, the sNDA submission for ruxolitinib cream in pediatric atopic dermatitis was filed with the FDA with approval anticipated in the second half of 2025.

•In October, Opzelura was granted a Notice of Compliance by Health Canada for the topical treatment of both mild to moderate atopic dermatitis and nonsegmental vitiligo in patients 12 years of age and older.

•In September, Incyte presented late-breaking Phase 3 results for retifanlimab (Zynyz) and initial data from the Phase 1 CDK2 inhibitor program at the 2024 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress.

1

◦Featured during the Presidential Symposium, the Phase 3 POD1UM-303/InterAACT2 trial for retifanlimab met the primary endpoint of progression free survival (PFS) and demonstrated improvement across secondary endpoints in patients with squamous cell anal carcinoma (SCAC) receiving retifanlimab in combination with platinum-based chemotherapy (carboplatin-paclitaxel). Incyte plans to file a supplemental Biologics License Application (sBLA) for retifanlimab in SCAC by the end of 2024. A potential approval in 2025 could represent the first PD-(L)1 antibody for patients with SCAC.

◦Phase 1 data of INCB123667, a highly selective and potentially first-in-class CDK2 inhibitor, were presented demonstrating single-agent antitumor activity across a range of doses and regimens, notably in patients with ovarian cancer and endometrial cancer whose tumors overexpress Cyclin E1. The Phase 1 trial of INCB123667 in combination with other agents is ongoing. Incyte plans to initiate a pivotal trial in ovarian cancer in 2025.

•In August, Incyte and its partner Syndax announced the U.S. Food and Drug Administration (FDA) approval of Niktimvo (axatilimab-csfr), an anti-CSF-1R antibody, for the treatment of chronic graft-versus-host disease (GVHD) after failure of at least two prior lines of systemic therapy in adult and pediatric patients. Niktimvo is the first approved anti-CSF-1R antibody targeting the drivers of inflammation and fibrosis seen in chronic GVHD. In September, Incyte and Syndax announced the New England Journal of Medicine publication of data from the pivotal AGAVE-201 trial of Niktimvo in chronic GVHD and the addition of Niktimvo to the NCCN Clinical Practice Guidelines in Oncology for the treatment of chronic GVHD.

•In August, Incyte announced positive topline results from the Phase 3 clinical study evaluating tafasitamab (Monjuvi) in relapsed or refractory follicular lymphoma (FL). The pivotal Phase 3 inMIND trial met the primary endpoint of PFS by investigator assessment in FL. The trial also met key secondary endpoints. No new safety signals with tafasitamab were observed. The full dataset is anticipated to be presented at an upcoming medical meeting in 2024 and Incyte expects to file an sBLA for tafasitamab in combination with lenalidomide and rituximab in FL by the end of 2024.
Jakafi:
Net product revenues for the third quarter 2024 of $741 million (+16% Y/Y):
▪Net product revenues were primarily driven by patient demand, which increased 10% in the third quarter of 2024 versus the same quarter in the prior year, with growth across all indications.
Opzelura:
Net product revenues for the third quarter 2024 of $139 million (+52% Y/Y):
▪Net product revenues of $119 million in the third quarter of 2024 in the U.S. were primarily driven by patient demand and refills in both atopic dermatitis (AD) and vitiligo.
▪Net product revenues of $20 million in the third quarter of 2024 ex-U.S. were primarily driven by sales in Germany and France.
Additional Pipeline Updates
Myeloproliferative Neoplasms (MPNs) and Graft-Versus-Host Disease (GVHD) – key highlights
▪A bioequivalence study of ruxolitinib extended-release (XR) is enrolling. The data are anticipated in the first half of 2025.
▪A Phase 2 trial evaluating the safety and efficacy of axatilimab in combination with ruxolitinib in patients with newly diagnosed chronic GVHD is enrolling.
▪Trials of ruxolitinib twice daily (BID) with BETi and zilurgisertib are ongoing. Additional data for BETi and zilurgisertib are anticipated in the fourth quarter of 2024.

▪The Phase 1 studies evaluating mCALR and JAK2V617Fi are ongoing and enrolling patients. Initial data for both studies are anticipated in 2025.
MPN and GVHD Programs Indication and status
Ruxolitinib XR (QD)
(JAK1/JAK2) Myelofibrosis, polycythemia vera and GVHD
Ruxolitinib + zilurgisertib
(JAK1/JAK2 + ALK2i) Myelofibrosis: Phase 2
Ruxolitinib + INCB57643
(JAK1/JAK2 + BETi) Myelofibrosis: Phase 2
Ruxolitinib + axatilimab1
(JAK1/JAK2 + anti-CSF-1R)
Chronic GVHD: Phase 2
Steroids + axatilimab1
(Steroids + anti-CSF-1R)
Chronic GVHD: Phase 3 in preparation
INCA33989
(mCALR) Myelofibrosis, essential thrombocythemia: Phase 1
INCB160058
(JAK2V617Fi) Myelofibrosis: Phase 1

1 Clinical development of axatilimab in GVHD conducted in collaboration with Syndax Pharmaceuticals.
Other Hematology/Oncology – key highlights
▪Following the announcement of the positive topline results from the Phase 3 study evaluating retifanlimab, a humanized monoclonal antibody targeting programmed cell death receptor-1 (PD-1), in non-small cell lung cancer (NSCLC), Incyte anticipates sharing the full dataset at an upcoming medical meeting in the fourth quarter of 2024.
▪The Phase 3 study evaluating tafasitamab in first-line diffuse large B-cell lymphoma (DLBCL) is ongoing. The Phase 3 data are anticipated in the first half of 2025.
▪The Phase 1 studies evaluating KRASG12D and TGFßR2×PD-1 are ongoing and enrolling patients. Initial data for both studies are anticipated in 2025.
Heme/Oncology Programs Indication and status
Tafasitamab (Monjuvi/Minjuvi)
(CD19)
Relapsed or refractory diffuse large B-cell lymphoma (DLBCL): Phase 3 (B-MIND)
First-line DLBCL: Phase 3 (frontMIND)
Relapsed or refractory follicular lymphoma (FL): Phase 3 (inMIND)
Retifanlimab (Zynyz)1
(PD-1)
Squamous cell anal cancer (SCAC): Phase 3 (POD1UM-303)
Non-small cell lung cancer (NSCLC): Phase 3 (POD1UM-304)
MSI-high endometrial cancer: Phase 2 (POD1UM-101, POD1UM-204)
INCB123667
(CDK2i) Solid tumors with Amplification/ Overexpression of CCNE1: Phase 1
INCB161734
(KRASG12D) Advanced metastatic solid tumors with a KRASG12D mutation: Phase 1
INCA33890
(TGFßR2×PD-1)2
Advanced or metastatic solid tumors: Phase 1

1 Retifanlimab licensed from MacroGenics.
2 Development in collaboration with Merus.
3

Inflammation and Autoimmunity (IAI) – key highlights
Ruxolitinib Cream
▪In September 2024, Incyte presented multiple datasets for ruxolitinib cream at the 2024 European Academy of Dermatology and Venereology (EADV) Congress including late-breaking oral presentations for vitiligo, atopic dermatitis, hidradenitis suppurativa (HS) and lichen planus.
▪Two Phase 3 trials (TRuE-PN1 and TRuE-PN2) evaluating ruxolitinib cream in prurigo nodularis (PN) are ongoing. The Phase 3 data are anticipated in the first half of 2025.
▪The Phase 3 trial for ruxolitinib cream in mild to moderate HS is on track to initiate in the first half of 2025 following achieving alignment on the study design with FDA. Ruxolitinib cream has the potential to provide a new therapeutic option for the approximately 150,000 mild to moderate HS patients in the U.S.
Povorcitinib (INCB54707)
▪In September 2024, Incyte presented long-term extension data at the 2024 EADV Congress from the Phase 2 randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of povorcitinib in patients with PN. In October 2024, two Phase 3 studies (STOP-PN1 and STOP-PN2) evaluating povorcitinib versus placebo were initiated and are enrolling.
▪The Phase 3 studies of povorcitinib in patients with hidradenitis suppurativa (STOP-HS1 and STOP-HS2) are enrolling well with data anticipated in the first quarter of 2025.
▪Two Phase 2 trials evaluating povorcitinib in asthma and chronic spontaneous urticaria (CSU) are enrolling. Data for CSU are anticipated in the first half of 2025 and data in asthma are anticipated in the second half of 2025.
INCB000262 (MRGPRX2)
▪Three clinical studies evaluating INCB000262 in CSU (Phase 2), chronic inducible urticaria (CIndu) (Phase 1b) and atopic dermatitis (AD) (Phase 2a) are ongoing. Data for all three studies are anticipated in the first quarter of 2025.
INCB000547 (MRGPRX4)
•The phase 2 clinical study evaluating MRGPRX4 in cholestatic pruritus is ongoing with data expected in the first quarter of 2025.
4

IAI and Dermatology Programs Indication and status
Ruxolitinib cream (Opzelura)1
(JAK1/JAK2)
Atopic dermatitis: Phase 3 pediatric study (TRuE-AD3)
Hidradenitis suppurativa: Phase 2; Phase 3 expected to initiate in 2025
Prurigo nodularis: Phase 3 (TRuE-PN1, TRuE-PN2)
Povorcitinib
(JAK1) Hidradenitis suppurativa: Phase 3 (STOP-HS1, STOP-HS2)
Vitiligo: Phase 3 (STOP-V1, STOP-V2)
Prurigo nodularis: Phase 3 (STOP-PN1, STOP-PN2)
Asthma: Phase 2
Chronic spontaneous urticaria: Phase 2
INCB000262
(MRGPRX2) Chronic spontaneous urticaria: Phase 2
Chronic inducible urticaria: Phase 1b
Atopic dermatitis: Phase 2a
INCB000547
(MRGPRX4) Cholestatic pruritus: Phase 2a
INCA034460
(anti-CD122) Vitiligo: Phase 1

1 Novartis’ rights to ruxolitinib outside of the United States under our Collaboration and License Agreement with Novartis do not include topical administration.
Other
Other Program Indication and Phase
Zilurgisertib
(ALK2) Fibrodysplasia ossificans progressiva: Pivotal Phase 2

2024 Third Quarter Financial Results

The financial measures presented in this press release for the three and nine months ended September 30, 2024 and 2023 have been prepared by the Company in accordance with U.S. Generally Accepted Accounting Principles ("GAAP"), unless otherwise identified as a Non-GAAP financial measure. Management believes that Non-GAAP information is useful for investors, when considered in conjunction with Incyte’s GAAP disclosures. Management uses such information internally and externally for establishing budgets, operating goals and financial planning purposes. These metrics are also used to manage the Company’s business and monitor performance. The Company adjusts, where appropriate, for expenses in order to reflect the Company’s core operations. The Company believes these adjustments are useful to investors by providing an enhanced understanding of the financial performance of the Company’s core operations. The metrics have been adopted to align the Company with disclosures provided by industry peers.

Non-GAAP information is not prepared under a comprehensive set of accounting rules and should only be used in conjunction with and to supplement Incyte’s operating results as reported under GAAP. Non-GAAP measures may be defined and calculated differently by other companies in our industry.

As changes in exchange rates are an important factor in understanding period-to-period comparisons, Management believes the presentation of certain revenue results on a constant currency basis in addition to reported results helps improve investors’ ability to understand its operating results and evaluate its performance in comparison to prior periods. Constant currency information compares results between periods as if exchange rates had remained constant period over period. The Company calculates constant currency by calculating current year results using prior year foreign currency exchange rates and generally refers to such amounts calculated on a constant currency basis as excluding the impact of foreign exchange or being on a constant currency basis. These results should be considered in addition to, not as a substitute for, results reported in accordance with GAAP. Results on a constant currency basis, as the Company presents them, may not be comparable to similarly titled measures used by other companies and are not measures of performance presented in accordance with GAAP.

On October 29, 2024 GlycoMimetics, Inc. (NASDAQ: GLYC) reported it has entered into an acquisition agreement with Crescent Biopharma, Inc. ("Crescent"), a privately held biotechnology company advancing a pipeline of oncology therapeutics designed to treat solid tumors (Press release, GlycoMimetics, OCT 29, 2024, View Source [SID1234647482]). Upon completion of the transaction, the Company plans to operate under the name Crescent Biopharma, Inc.

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In support of the acquisition, a syndicate of investors led by Fairmount, Venrock Healthcare Capital Partners, BVF Partners, and a large investment management firm, with participation from Paradigm BioCapital, RTW Investments, Blackstone Multi-Asset Investing, Frazier Life Sciences, Commodore Capital, Perceptive Advisers, Deep Track Capital, Boxer Capital Management, Soleus, Logos Capital, Driehaus Capital Management, Braidwell LP, and Wellington Management, has committed $200 million to purchase GlycoMimetics common stock and GlycoMimetics pre-funded warrants to purchase its common stock. The transaction is expected to close in the second quarter of 2025. The financing is expected to close immediately following the completion of the transaction. The Company’s cash balance at closing is anticipated to fund operations through 2027, including advancement of the Company’s lead program CR-001, a tetravalent PD-1 x VEGF bispecific antibody, through preliminary proof of concept clinical data in solid tumor patients expected in the second half of 2026.

"Crescent was founded to harness recent breakthroughs in immuno-oncology and antibody-drug conjugates that pave the way for a next generation of therapies for patients with solid tumors," said Jonathan Violin, interim CEO at Crescent and Venture Partner at Fairmount. "Our lead program CR-001 was precision engineered to impart a cooperative binding pharmacology for VEGF x PD-1 bispecific blockade; this mechanism recently demonstrated superior efficacy to the anti-PD1 antibody pembrolizumab in a third party head-to-head Phase 3 clinical trial. The specific level of cooperativity engineered into CR-001 reflects a delicate mechanistic balance, which is essential to our confidence in this program. This transaction and financing enable a potentially rapid development path for CR-001, and for the antibody drug conjugate programs CR-002 and CR-003."

Crescent is the fifth company to launch with assets discovered and developed by Paragon Therapeutics. CR-001, a tetravalent PD-1 x VEGF bispecific antibody, matches the format and pharmacology of ivonescimab, which delivered superior efficacy compared to the current market leader pembrolizumab in a large third party Phase 3 trial. In addition to CR-001, Crescent is developing CR-002 and CR-003, antibody-drug conjugates (ADCs) against undisclosed targets using topoisomerase inhibitor payloads; ADCs with topoisomerase inhibitor payloads have shown improved efficacy and safety compared to ADCs with alternative payloads.

The Company anticipates that the IND for CR-001 will be filed in 4Q25 or 1Q26, and interim Phase 1 data from patients is expected in 2H26. CR-002, Crescent’s first ADC program, is designed to be best-in-class and is expected to initiate Phase 1 in 2026; the Company plans to disclose the target for CR-002 as the program approaches the clinic.

The Company intends to determine potential paths forward for its late stage clinical candidate, Uproleselan, including by supporting continued data analyses of Uproleselan from NCI, its corporate partner for China, Apollomics, and investigator initiated studies.

"We are confident that our transaction with Crescent represents a significant opportunity for GlycoMimetics and its stockholders," said Harout Semerjian, CEO of GlycoMimetics. "This transaction is the result of a comprehensive strategic review, and with additional funding for Crescent’s portfolio of novel biologics, we believe the company is well-positioned to carry forward the mission of seeking to improve the lives of patients."

About the Proposed Transactions

Under the terms of the acquisition agreement, the pre-acquisition GlycoMimetics stockholders are expected to own approximately 3.1% of the combined Company and the pre-acquisition Crescent stockholders (inclusive of those investors participating in the pre-closing financing) are expected to own approximately 96.9% of the company. The percentage of the company that GlycoMimetics’s stockholders will own as of the closing of the acquisition is subject to adjustment based on the amount of GlycoMimetics’s net cash at the closing date.

The transaction has received approval by the Board of Directors of both companies and is expected to close in the second quarter of 2025, subject to certain closing conditions, including, among other things, approval by the stockholders of each company and the satisfaction of customary closing conditions.

The company will be named Crescent Biopharma, Inc. and be led by Jonathan Violin, Ph.D., Crescent’s interim Chief Executive Officer, who will be joined on Crescent’s Board of Directors by Peter Harwin, Managing Member of Fairmount. Wedbush PacGrow is serving as strategic advisor and Gibson, Dunn & Crutcher LLP is serving as legal counsel to Crescent. Jefferies, TD Cowen, Stifel, and LifeSci Capital are serving as the placement agents to Crescent. Covington is serving as legal counsel to the placement agents. Lucid Capital Markets is serving as financial advisor and Sidley Austin is serving as legal counsel to GlycoMimetics.

Conference Call Details

The companies plan to hold a joint conference call on October 29, 2024 at 8:00 AM EDT to discuss the merger details.

To access the call by phone, please go to this registration link and you will be provided with dial in details. Participants are encouraged to connect 15 minutes in advance of the scheduled start time.

A live webcast of the call will be available on the "Investors" tab on the GlycoMimetics website. A webcast replay will be available for 30 days following the call.

On October 29, 2024 Exelixis, Inc. (Nasdaq: EXEL) reported financial results for the third quarter of 2024, provided an update on progress toward achieving key corporate objectives, and detailed its recent and anticipated commercial, clinical and pipeline development milestones (Press release, Exelixis, OCT 29, 2024, View Source [SID1234647479]).

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"The favorable ruling on our cabozantinib intellectual property estate and recently announced zanzalintinib development collaboration with Merck have generated important momentum to drive future growth across all components of our business," said Michael M. Morrissey, Ph.D., President and CEO, Exelixis. "We are increasing 2024 full year guidance for total and net product U.S. revenues based on the strong commercial performance of the cabozantinib franchise in the third quarter. We continue to execute on our plans for potential cabozantinib label expansions in neuroendocrine tumors and prostate cancer, with the final results from CABINET published in The New England Journal of Medicine in September and our partner Ipsen’s regulatory submission in Europe."

Dr. Morrissey continued: "Importantly, the zanzalintinib development program, which is now the subject of six ongoing or planned phase 3 pivotal trials, including two new renal cell carcinoma studies as part of our collaboration with Merck, headlines our emerging pipeline of novel agents with the potential to improve standards of care for patients with cancer. At the same time, we are accelerating our early-stage clinical pipeline with XL309, XB010 and XL495 in phase 1 development. I want to thank everyone at Exelixis for their hard work and dedication as we continue driving value for shareholders and innovating on behalf of the patients we serve."

Third Quarter 2024 Financial Results

Total revenues for the quarter ended September 30, 2024 were $539.5 million, as compared to $471.9 million for the comparable period in 2023.

Total revenues for the quarter ended September 30, 2024 included net product revenues of $478.1 million, as compared to $426.5 million for the comparable period in 2023. The increase in net product revenues was primarily due to an increase in sales volume and average net selling price.

Collaboration revenues, composed of license revenues and collaboration services revenues, were $61.5 million for the quarter ended September 30, 2024, as compared to $45.4 million for the comparable period in 2023. The increase in collaboration revenues was primarily related to an increase in milestone-related revenues recognized in the quarter and higher royalty revenues for the sales of cabozantinib outside of the U.S. generated by Exelixis’ collaboration partners, Ipsen Pharma SAS (Ipsen) and Takeda Pharmaceutical Company Limited, partially offset by a decrease in development cost reimbursements earned.

Research and development expenses for the quarter ended September 30, 2024 were $222.6 million, as compared to $332.6 million for the comparable period in 2023. The decrease in research and development expenses was primarily related to decreases in license and other collaboration costs.

Selling, general and administrative expenses for the quarter ended September 30, 2024 were $111.8 million, as compared to $138.1 million for the comparable period in 2023. The decrease in selling, general and administrative expenses was primarily related to decreases in corporate giving, stock-based compensation expenses and legal and advisory fees.

Impairment of long-lived assets for the quarter ended September 30, 2024 of $51.7 million was related to the non-cash asset impairment charge to certain of Exelixis’ leased facilities which are currently not in use and may be subleased.

Provision for income taxes for the quarter ended September 30, 2024 was $36.8 million, as compared to $4.8 million for the comparable period in 2023.

GAAP net income for the quarter ended September 30, 2024 was $118.0 million, or $0.41 per share, basic and $0.40 per share, diluted, as compared to GAAP net income of $1.0 million, or $0.00 per share, basic and diluted, for the comparable period in 2023. GAAP net income per share for the quarter ended September 30, 2024 was favorably impacted by lower weighted-average common shares outstanding for the quarter ended September 30, 2024, as compared to the comparable period in 2023, as a result of the stock repurchase programs.

Non-GAAP net income for the quarter ended September 30, 2024 was $135.7 million, or $0.47 per share, basic and diluted, as compared to non-GAAP net income of $32.1 million, or $0.10 per share, basic and diluted, for the comparable period in 2023.

Non-GAAP Financial Measures

To supplement Exelixis’ financial results presented in accordance with U.S. Generally Accepted Accounting Principles (GAAP), Exelixis presents non-GAAP net income (and the related per share measures), which excludes from GAAP net income (and the related per share measures) stock-based compensation expense, adjusted for the related income tax effect for all periods presented.

Exelixis believes that the presentation of these non-GAAP financial measures provides useful supplementary information to, and facilitates additional analysis by, investors. In particular, Exelixis believes that these non-GAAP financial measures, when considered together with its financial information prepared in accordance with GAAP, can enhance investors’ and analysts’ ability to meaningfully compare Exelixis’ results from period to period, and to identify operating trends in Exelixis’ business. Exelixis has excluded stock-based compensation expense, adjusted for the related income tax effect, because it is a non-cash item that may vary significantly from period to period as a result of changes not directly or immediately related to the operational performance for the periods presented. Exelixis also regularly uses these non-GAAP financial measures internally to understand, manage and evaluate its business and to make operating decisions.

These non-GAAP financial measures are in addition to, not a substitute for, or superior to, measures of financial performance prepared in accordance with GAAP. Exelixis encourages investors to carefully consider its results under GAAP, as well as its supplemental non-GAAP financial information and the reconciliation between these presentations, to more fully understand Exelixis’ business. Reconciliations between GAAP and non-GAAP results are presented in the tables of this release.

2024 Financial Guidance

Exelixis is providing the following updated financial guidance for fiscal year 2024(1):

Current Guidance
(provided on October 29, 2024)
Previous Guidance
(provided on August 6, 2024)
Total revenues
$2.150 billion – $2.200 billion
$1.975 billion – $2.075 billion
Net product revenues(2)
$1.775 billion – $1.825 billion
$1.650 billion – $1.750 billion
Cost of goods sold ~4.5% of net product revenues 4% – 5% of net product revenues
Research and development expenses
$925 million – $950 million(3)
$925 million – $975 million(4)
Selling, general and administrative expenses(5)
$475 million – $500 million
$450 million – $500 million
Effective tax rate
21% – 22%
20% – 22%

____________________
(1) 2024 financial guidance excludes expenses related to the restructuring plan announced in January 2024 and impairment of long-lived assets announced in October 2024.
(2) Exelixis’ 2024 net product revenues guidance range includes the impact of a U.S. wholesale acquisition cost increase of 2.2% for both CABOMETYX and COMETRIQ effective on January 1, 2024.
(3) Includes $30 million of non-cash stock-based compensation expense.
(4) Includes $40 million of non-cash stock-based compensation expense.
(5) Includes $60 million of non-cash stock-based compensation expense.

Corporate Highlights

Favorable Ruling in Second Cabozantinib Abbreviated New Drug Application (ANDA) Litigation Against MSN Pharmaceuticals, Inc. (MSN). In October, the U.S. District Court for the District of Delaware (the District Court) ruled in Exelixis’ favor, rejecting MSN’s challenge to three Orange Book-listed patents related to cabozantinib (U.S. Patents No. 11,091,439 (crystalline salt forms), 11,091,440 (pharmaceutical composition) and 11,098,015 (methods of treatment)), which expire January 15, 2030. The District Court’s decision follows an earlier stipulation that MSN’s proposed generic cabozantinib product (ANDA No. 213878) infringes the ’439, ’440, and ’015 patents. The District Court also ruled that Exelixis’ U.S. Patent No. 11,298,349 (pharmaceutical composition) is not invalid and not infringed by MSN’s proposed ANDA product. To Exelixis’ knowledge, the U.S. Food and Drug Administration (FDA) has not yet granted tentative approval of MSN’s proposed ANDA product. On October 23, 2024, the District Court entered final judgment reflecting the opinion. Based on the District Court’s final judgment, should the FDA ultimately approve MSN’s ANDA, the effective date of any such approval and commercial launch in the U.S. of MSN’s proposed ANDA product shall not be a date earlier than January 15, 2030, subject to Exelixis’ potential additional regulatory exclusivity. The District Court’s judgment is also subject to appeal by either party.

New Clinical Development Collaboration with Merck to Evaluate Zanzalintinib in Combination with KEYTRUDA (pembrolizumab) in Head and Neck Cancer and with WELIREG (belzutifan) in Renal Cell Carcinoma (RCC). In October, Exelixis and Merck (known as MSD outside of the U.S. and Canada) announced a clinical development collaboration to evaluate zanzalintinib in combination with KEYTRUDA in head and neck squamous cell carcinoma (HNSCC), and zanzalintinib with WELIREG in RCC. Under the terms of the collaboration, Merck will supply KEYTRUDA, its anti-PD-1 therapy, for the ongoing, Exelixis-sponsored phase 3 STELLAR-305 pivotal trial in previously untreated PD-L1 positive recurrent or metastatic HNSCC. In addition, Merck will sponsor a phase 1/2 trial and two phase 3 pivotal trials evaluating zanzalintinib in combination with WELIREG, its oral hypoxia-inducible factor-2 alpha (HIF-2α) inhibitor, in RCC. Merck will fund one of these phase 3 studies, and Exelixis will co-fund the phase 1/2 trial and the other phase 3 study, as well as supply zanzalintinib and cabozantinib. Exelixis maintains all global commercial and marketing rights to zanzalintinib.

Stock Repurchase Program. In August, Exelixis announced that the company’s Board of Directors authorized the repurchase of up to $500 million of the company’s common stock through the end of 2025, the third stock repurchase program undertaken by Exelixis since March 2023. Under this program, as of September 30, 2024, Exelixis has repurchased $12.4 million of the company’s common stock, at an average price of $25.61 per share.

Cabozantinib Highlights

Cabozantinib Franchise Net Product Revenues and Royalties. Net product revenues generated by the cabozantinib franchise in the U.S. were $478.1 million during the third quarter of 2024, with net product revenues of $475.7 million from CABOMETYX (cabozantinib) and $2.4 million from COMETRIQ (cabozantinib). Based upon cabozantinib-related net product revenues generated by Exelixis’ collaboration partners during the quarter ended September 30, 2024, Exelixis earned $41.8 million in royalty revenues.

Exelixis’ Partner Ipsen Opted into Phase 3 CABINET Pivotal Trial in Advanced Neuroendocrine Tumors (NET) and Submitted an Extension of Indication Marketing Authorization to the European Medicines Agency (EMA). In July, Ipsen announced it opted into the phase 3 CABINET pivotal trial, expanding the existing collaboration and license agreement with Exelixis and permitting Ipsen to seek potential marketing authorizations for CABOMETYX in advanced pancreatic NET (pNET) and extra-pancreatic NET (epNET) from regulatory authorities outside of the U.S. and Japan. As part of the agreement, Exelixis is eligible to receive reimbursement of a portion of costs related to the trial, as well as milestone payments for potential future regulatory action by the EMA. In September, Ipsen announced it submitted an extension of indication Marketing Authorization to the EMA for CABOMETYX in advanced NET. These announcements were based on detailed results from CABINET, which evaluated cabozantinib compared with placebo in patients with previously treated advanced pNET and advanced epNET. CABINET is sponsored by the National Cancer Institute (NCI), part of the National Institutes of Health, and led by the NCI-funded Alliance for Clinical Trials in Oncology.

FDA Accepted Supplemental New Drug Application (sNDA) for Cabozantinib for Patients with Advanced NET. In August, Exelixis announced that the FDA accepted its sNDA for cabozantinib for patients with previously treated advanced pNET and for patients with previously treated advanced epNET. The FDA assigned a standard review with a Prescription Drug User Fee Act (PDUFA) target action date of April 3, 2025. The FDA also granted orphan drug designation to cabozantinib for the treatment of pNET. The sNDA was based on results from the CABINET trial.

Final Results from Phase 3 CABINET Pivotal Trial Evaluating Cabozantinib in Advanced NET Presented at the 2024 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress and Published in The New England Journal of Medicine (NEJM). In September, detailed final results from CABINET were presented at the 2024 ESMO (Free ESMO Whitepaper) Congress and published in NEJM. The results demonstrated continued improvement with cabozantinib in the primary endpoint of progression-free survival by blinded independent central review, and additional analyses suggest benefits with cabozantinib across all clinical subgroups examined, including primary tumor site, grade and prior systemic anti-cancer therapy.

Final Overall Survival (OS) Results from Phase 3 CONTACT-02 Pivotal Trial Evaluating Cabozantinib in Combination with Atezolizumab in Metastatic Castration-Resistant Prostate Cancer (mCRPC) Presented at the 2024 ESMO (Free ESMO Whitepaper) Congress. In September, the final analysis of OS from the phase 3 CONTACT-02 pivotal study was presented at the 2024 ESMO (Free ESMO Whitepaper) Congress. The results of the final OS analysis showed a trend that favored the combination of cabozantinib and atezolizumab but was not statistically significant. The trend in OS benefit was consistently observed in key subgroups, including in patients with liver metastases, a subgroup of mCRPC patients with the poorest prognosis in need of new treatment options, which Exelixis anticipates will grow in the coming years. CONTACT-02 evaluated cabozantinib in combination with atezolizumab compared with a second novel hormonal therapy (NHT) in patients with measurable, extra-pelvic mCRPC who have progressed after treatment with one prior NHT. Exelixis intends to submit an sNDA to the FDA for cabozantinib in combination with atezolizumab for mCRPC in the fourth quarter of 2024.

Pipeline Highlights

Enrollment Completion for Zanzalintinib Phase 3 STELLAR-303 Study in Metastatic Colorectal Cancer (CRC) and Announcement of STELLAR-311 Pivotal Trial Evaluating Zanzalintinib in NET. In August, Exelixis announced that enrollment was completed in the STELLAR-303 phase 3 pivotal study. STELLAR-303 is evaluating zanzalintinib in combination with atezolizumab compared with regorafenib in patients with metastatic refractory CRC that is not microsatellite instability-high or mismatch repair-deficient. The primary endpoint in the study is OS in the patients without liver metastases. Exelixis anticipates preliminary results from the study in 2025. Additionally, Exelixis announced plans to initiate STELLAR-311, a new phase 3 pivotal trial evaluating zanzalintinib compared with everolimus as a first oral therapy in patients with advanced NET, regardless of site of origin, in the first half of 2025.

Initiation of Phase 1 Clinical Trial Evaluating XB010 in Patients with Advanced Solid Tumors. In August, Exelixis announced the initiation of the dose-escalation stage of the first-in-human phase 1 clinical trial of XB010 in patients with locally advanced or metastatic solid tumors. XB010, an antibody-drug conjugate (ADC) consisting of a monomethyl auristatin E payload conjugated to a monoclonal antibody targeting the tumor antigen 5T4, is the first custom ADC generated through Exelixis’ biotherapeutics collaboration network. The dose-escalation stage of this global phase 1 study is evaluating XB010 as a single agent and in combination with pembrolizumab to inform the cohort-expansion stage. The expansion cohorts are designed to further assess the tolerability and activity of monotherapy and of the combination in specific indications.

Initiation of Phase 1 Clinical Trial Evaluating XL495 in Patients with Advanced Solid Tumors. Today, Exelixis announced the initiation of the dose-escalation stage of the first-in-human phase 1 clinical trial of XL495 in patients with advanced solid tumors. XL495 is a novel, potent, small molecule inhibitor of PKMYT1. The dose-escalation stage of this phase 1 study is designed to determine the maximum tolerated dose of XL495. The expansion cohorts are designed to further assess the tolerability and activity of XL495 both as monotherapy and in combination with select cytotoxic agents in tumor-specific indications.

Basis of Presentation

Exelixis has adopted a 52- or 53-week fiscal year that generally ends on the Friday closest to December 31. For convenience, references in this press release as of and for the fiscal periods ended September 27, 2024 and September 29, 2023, are indicated as being as of and for the periods ended September 30, 2024 and September 30, 2023.

Conference Call and Webcast

Exelixis management will discuss the company’s financial results for the third quarter of 2024 and provide a general business update during a conference call beginning at 5:00 p.m. ET / 2:00 p.m. PT today, Tuesday, October 29, 2024.

To access the conference call, please register using this link. Upon registration, a dial-in number and unique PIN will be provided to join the call. To access the live webcast link, log onto www.exelixis.com and proceed to the Event Calendar page under the Investors & News heading. A webcast replay of the conference call will also be archived on www.exelixis.com for one year.

On October 29, 2024 GSK plc (LSE/NYSE: GSK) and Chimagen Biosciences (Chimagen), a privately held biotechnology company, reported an agreement for GSK to acquire CMG1A46, a clinical-stage dual CD19 and CD20-targeted T cell-engager (TCE), from Chimagen for $300 million upfront (Press release, GlaxoSmithKline, OCT 29, 2024, View Source [SID1234647480]). GSK plans to develop and commercialise CMG1A46 with a focus on B cell-driven autoimmune diseases, such as systemic lupus erythematosus (SLE) and lupus nephritis (LN), with potential to expand into related autoimmune diseases.

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For over a decade, GSK has been a pioneer in the treatment of lupus. This agreement underscores the importance of novel therapeutic approaches to address the heterogeneity of lupus manifestations and the continued burden, particularly in patients who suffer from severe disease and are refractory to current standard of care.1

Tony Wood, Chief Scientific Officer, GSK, said: "Through our work in systemic lupus erythematosus and lupus nephritis, we increasingly understand the underlying drivers of B cell-driven diseases. As a novel therapeutic option directed at deep B cell depletion, CMG1A46 offers exciting potential which we are pleased to take forward to address unmet need in lupus and related autoimmune conditions."

CD20 is an established target in the treatment of autoimmune diseases and there is growing clinical evidence that CD19 shows promise as a differentiated therapeutic approach given its presence on more B cell types.2 In preclinical studies, CMG1A46, designed to target both CD19 and CD20, has shown rapid, deep B cell depletion both in the bloodstream and in tissues which could lead to more durable responses in patients.

Zhenhao Zhou, Chief Executive Officer, Chimagen, said: "We are excited by the potential of CMG1A46 to improve the lives of patients suffering from autoimmune conditions and grateful to have GSK accelerate that vision. This agreement provides further validation of our proprietary T cell-engager platform, and we are eager to continue our mission of developing novel multi-specific antibody therapeutics."

CMG1A46 is currently in phase I clinical trials in leukaemia and lymphoma in both the US and China. GSK aims to begin a phase I trial in lupus in 2025.

Terms of the agreement
Under the terms of this agreement, GSK will pay $300 million upfront to acquire full global rights to CMG1A46. In addition, Chimagen will be eligible to receive success-based development and commercial milestone payments for CMG1A46 totalling $550 million.

This agreement is subject to customary conditions, including applicable regulatory agency clearances under the Hart-Scott-Rodino Act in the US.

About CMG1A46
CMG1A46, a dual CD19 and CD20-targeted T cell-engager (TCE), is an IgG-like molecule with high affinity for CD19 and CD20 positive B cells and low affinity for CD3, which could lower toxicities typically associated with TCEs.

On October 29, 2024 Curis, Inc. ("Curis") (NASDAQ: CRIS), a biotechnology company focused on the development of emavusertib (CA-4948), an orally available, small molecule IRAK4 inhibitor, reported that it has entered into a definitive agreement with a combination of existing and new investors for the purchase of 2,398,414 shares of its common stock in a registered direct offering priced at-the-market under Nasdaq rules (Press release, Curis, OCT 29, 2024, View Source [SID1234647478]). In a concurrent private placement, Curis also agreed to issue to the investors in the registered direct offering unregistered warrants to purchase up to an aggregate of 2,398,414 shares of common stock. The unregistered warrants to be issued in the concurrent private placement will have an exercise price of $4.92 per share of common stock, will be exercisable immediately and will expire five years following the issuance date. The combined purchase price for one share of common stock and the associated unregistered warrant is $5.045.

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Gross proceeds to Curis from the offering are expected to be approximately $12.1 million, before deducting the placement agents’ fees and other offering expenses payable by Curis. Curis intends to use the net proceeds from the offering on research, development, working capital, and other general corporate purposes. The registered direct offering and concurrent private placement are each expected to close on or about October 30, 2024, subject to the satisfaction of customary closing conditions.

Truist Securities and Laidlaw & Company (U.K.) Ltd. are acting as placement agents for the registered direct offering and the concurrent private placement.

The shares of common stock offered in the registered direct offering (but excluding the unregistered warrants to be issued in the concurrent private placement and shares of common stock underlying the unregistered warrants) are being offered by Curis pursuant to a shelf registration statement on Form S-3 (File No. 333-276950) that was filed with the U.S. Securities and Exchange Commission ("SEC") on February 8, 2024 and declared effective by the SEC on April 12, 2024. A prospectus supplement relating to and describing the terms of the registered direct offering will be filed with the SEC and will be available on the SEC’s website at www.sec.gov. The registered direct offering is being made only by means of a prospectus and related prospectus supplement. When available, electronic copies of the prospectus supplement and the accompanying prospectus may also be obtained from Truist Securities, Inc., Attention: Prospectus Department, 3333 Peachtree Road NE, 9th floor, Atlanta, Georgia 30326, by telephone at (800) 685-4786, or by email at [email protected]; and Laidlaw & Company (U.K.) Ltd., Attention: [email protected].

The unregistered warrants are being offered in the concurrent private placement pursuant to an exemption from the registration requirements of the Securities Act of 1933, as amended (the "Securities Act"), provided in Section 4(a)(2) of the Securities Act and/or Regulation D promulgated thereunder and, along with the shares of common stock underlying such unregistered warrants, have not been registered under the Securities Act or applicable state securities laws. Curis has agreed to file a resale registration statement with the SEC covering the resale of the shares of common stock underlying the unregistered warrants.

This press release shall not constitute an offer to sell or the solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any state or other jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or other jurisdiction.