On January 12, 2024 Telix Pharmaceuticals Limited (ASX: TLX, Nasdaq: TLX, Telix, the Company) reported it has entered into an asset purchase agreement with antibody engineering company ImaginAb, Inc. (ImaginAb) to acquire a pipeline of next-generation therapeutic candidates, proprietary novel biologics technology platform, and a protein engineering and discovery research facility to enhance existing innovation capabilities (Press release, Telix Pharmaceuticals, JAN 12, 2025, View Source [SID1234649621]).

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This transaction adds a pipeline of early-stage drug candidates against high-value targets including DLL3[1] and integrin αvβ6[2], as well as several other novel targets in discovery stage. These next generation drug candidates fit synergistically with Telix’s therapeutics pipeline, enabling expansion to future therapy areas with unmet clinical need. The acquired intellectual property utilizes small engineered antibody formats that enable highly specific cancer targeting, combined with fast tumor uptake and blood clearance. This technology has the potential to be highly effective for imaging and treating tumors with a broad range of radioisotopes, with alpha emitters of particular interest.

The transaction also includes a state-of-the-art research facility in California, staffed by a talented team of discovery, protein engineering and radiopharmaceutical development experts. Together, these assets will provide Telix with further in-house capabilities in antibody engineering and preclinical development, as well as a novel biologics platform to create the next generation of Telix precision medicine and therapeutic products, beyond the current clinical-stage pipeline.

Richard Valeix, Chief Executive Officer, Therapeutics, Telix, said, "The combination of a proprietary drug discovery platform, pipeline of promising theranostic assets and a talented team of subject matter experts will enhance Telix’s research and innovation capability now and into the future. This acquisition will enable Telix to explore new disease areas with state-of-the-art radiotherapeutic technology."

Dr. Anna M. Wu, Co-Founder and Board Member, ImaginAb, added, "As the radiopharmaceutical sector gains momentum there is a significant need for targeting agents to be more selective, deliver less off-target radiation, and better match the pharmacology and radiobiology of a given radionuclide. The team’s deep expertise in antibody engineering and the resulting development of a valuable, proprietary platform technology has led to clinical proof-of-concept. Telix is the right partner to unlock the future therapeutic potential of this platform."

Transaction details

Telix will acquire these assets through an asset purchase agreement with a concurrent technology license agreement to be signed at closing. The purchase price for the transaction is US$45 million (AU$73 million)[3], comprised of US$10 million in cash and US$31 million in equity at closing, and a deferred payment of up to US$4 million in equity at the conclusion of a 15-month indemnity period.

Upon achievement of specific key development and commercial milestones, Telix will pay up to a total of US$185 million (AU$299 million), a portion of which may be paid in cash or equity at Telix’s election[4]. Royalties are also payable on net sales in the low single digits on a limited number of platform and early-stage products after the first four products have been developed, as well as single-digit sublicense fees, as applicable.

Telix will issue ordinary shares to ImaginAb within its Listing Rule 7.1 placement capacity as consideration for the acquisition. Upfront equity consideration will be subject to voluntary escrow (lock-up/leak-out) restrictions with equal tranches being released from escrow 60, 90 and 120 days after closing. Completion of the transaction is subject to customary conditions, including regulatory approvals and other third-party consents. Telix cannot guarantee this transaction will close in any specific timeframe or on the terms summarized here, if at all.

On January 12, 2025 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 an update on its programs, development plans and guidance on key milestones expected in 2025, to be presented at the 43rd Annual J.P. Morgan Healthcare Conference in San Francisco, California (Press release, Molecular Partners, JAN 12, 2025, View Source [SID1234649620]).

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"We are excited to enter 2025 with upcoming key value inflection points, on the Radio-DARPin side as well as Switch-DARPin and clinical T-cell engagers, to build on our achievements through 2024. Our recently expanded strategic partnership with Orano Med ensures us access to 212Pb, to arm our Radio-DARPins for up to 10 products. MP0712, our most advanced Radio-DARPin targeting DLL3, is moving into clinical development in 2025. Further, we have selected Mesothelin as the second target in the Orano Med partnership, with unique DARPin binders that only bind to juxtamembrane Meso while not being inhibited by the shed target," said Patrick Amstutz, Ph.D., CEO of Molecular Partners.

Molecular Partners has further strengthened and expanded its agreement with Orano Med for co-development of up to ten 212Pb-based Radio-DARPins. Molecular Partners holds commercialization rights to MP0712, which is the most advanced program, as well as the second nominated Radio-DARPin candidate, which targets the membrane-proximal portion of cell surface glycoprotein Mesothelin (MSLN). Orano Med will ensure the production of the 212Pb-based Radio-DARPins for clinical trials and commercialization. Further details on this second candidate are scheduled to be unveiled at the Annual Meeting of the American Association of Cancer Research (AACR) (Free AACR Whitepaper) in Q2 2025.

Patrick Amstutz continued, "We are equally excited that our work on the MP0533 candidate in R/R AML is starting to yield encouraging results. As we work to implement our previously discussed protocol amendments, we are already starting to see patients benefit from treatment in our ongoing cohort 8, where we introduced an additional dosing timepoint early on. These preliminary data provide us with reassurance that our strategy to further densify early dosing has merit and could enable more patients to benefit longer from MP0533."

Cash and Cash Equivalents:
As of Dec 31 2024, Molecular Partners reports cash and cash equivalents of CHF 149 M (unaudited) and will provide full YE financial results on March 6, 2025.

Key current program status updates include:

MP0712 & Radio-DARPin pipeline

The Investigational New Drug (IND) application for MP0712, a 212Pb Radio-DARPin candidate against the tumor-associated protein delta-like ligand 3 (DLL3), is in preparation. Dialogue with the U.S. Food and Drug Administration (FDA) is ongoing and Molecular Partners and Orano Med anticipate submitting the IND application for MP0712 in H1 2025, with the first-in-human study to start following regulatory clearance.

The IND submission is being built, in part, on strong MP0712 preclinical results, including new in vivo data presented at the European Association of Nuclear Medicine Congress in October 2024 and the European Targeted Radiopharmaceuticals Summit in December 2024. MP0712 demonstrated high affinity and specificity for DLL3, which is a highly relevant target for radiopharmaceutical therapy. DLL3 has been shown to have homogeneous expression in tumors of patients with small cell lung cancer, and expression in healthy tissues is low.

The second Radio-DARPin program co-developed with Orano Med targets MSLN, which is overexpressed across several cancers with high unmet need, such as ovarian cancer, and largely absent from healthy tissues. The development of therapeutics against MSLN has been hampered by high shedding of MSLN. Leveraging the unique DARPin properties, Molecular Partners has developed Radio-DARPins able to selectively bind to the membrane-proximal portion of MSLN present on cells and are therefore not impacted by shed MSLN.

In addition to the above updates, Molecular Partners continues to progress its Radio-DARPin Therapy (RDT) portfolio of projects in partnership with Novartis and is evaluating additional targets for RDT programs.

MP0533 (multispecific T cell engager)

MP0533 is currently being evaluated in a Phase 1/2a clinical trial for relapsed/refractory acute myeloid leukemia (AML) and myelodysplastic syndrome/AML (ClinicalTrials.gov: NCT05673057). Dose escalation in cohort 1–7 showed an acceptable safety profile and initial activity yet unsustained responses (four responders reported and encouraging blast reductions across additional patients), as presented in December 2024 at the American Society of Hematology (ASH) (Free ASH Whitepaper) meeting.

In the currently ongoing cohort 8, in which an additional early dosing timepoint was introduced to allow steeper and more frequent dosing to reach the MP0533 target dose faster, increased rates and depth of responses are being observed, with three out of the first eight evaluable patients demonstrating responses to-date (data cutoff 16 December 2024). Molecular Partners has submitted an amendment to the study protocol to improve the exposure profile of MP0533 and to further deepen and expand responses being observed in cohort 8. Data on the amended dosing scheme are expected in 2025.

MP0533 is a novel tetraspecific T cell engaging DARPin which simultaneously targets the three tumor-associated antigens (TAAs) CD33, CD123, and CD70, as well as CD3 on T cells. The mechanism of action of MP0533 is designed to preferentially kill AML cells that express at least two of the three TAAs while sparing healthy cells, which express only one or none of these targets. The immune activation against the malignant cells is achieved through CD3-mediated T cell engagement.

Switch-DARPin Platform (next-generation immune cell engagers)

Preclinical proof-of-concept in a solid tumor model for the novel T cell engager Switch-DARPin was presented at the Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) in November. The presented data provide further validation of Switch-DARPins showing that conditional Tcell activation with potent co-stimulation in solid tumors, but not in healthy tissues, is feasible.

Specifically, the CD3 Switch-DARPin molecule was shown to effectively induce potent tumor regression in vivo. Reduced cytokine release was observed in healthy tissues compared to tumor tissue. Cytokine release syndrome (CRS) is a significant toxicity event that has been observed with many T cell engagers in the clinic. As such, masking CD3 may prevent T cell activation in the absence of tumor antigens and allow for "silent" T cell engagers outside of tumors, thereby reducing the risk of CRS and providing a better safety profile to T cell engagers. In addition, co-engagement of CD2 led to sustained T cell activation and cytotoxic capacity, thereby enabling the development of potent T cell engagers with improved therapeutic window. Molecular Partners plans to present further in vivo data on the CD3 Switch-DARPin at the AACR (Free AACR Whitepaper) Annual Meeting in Q2 2025.

MP0317 (localized agonist)

Molecular Partners presented comprehensive biomarker analyses from the completed Phase 1 clinical trial of the CD40 agonist MP0317 in solid tumors at SITC (Free SITC Whitepaper) in November 2024. MP0317 is designed to activate immune cells specifically within the tumor microenvironment by anchoring to fibroblast activation protein (FAP) which is expressed in high amounts in the stroma of various solid tumors. This tumor-localized approach has the potential to deliver greater efficacy with fewer side effects compared to systemic CD40-targeting therapies.

Molecular Partners is in discussion with leading academic centers regarding potential investigator-initiated combination trials of MP0317 in 2025, in combination with immune checkpoint inhibitors and additional standard of care.

J.P. Morgan Presentation Details:

Presenter: Molecular Partners CEO Patrick Amstutz
Time: January 15, 2025, at 9:00 AM PST (6:00 PM CET)
Location: Westin St. Francis, Elizabethan A Ballroom, San Francisco, CA

A webcast will be accessible on the Molecular Partners website, under the Events tab.

On January 12, 2025 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, and Orano Med, a clinical-stage radiopharmaceutical company and a pioneer in the development of targeted alpha-particle therapies (TAT) with 212Pb (lead-212), reported the expansion of their strategic collaboration (Press release, Molecular Partners, JAN 12, 2025, View Source [SID1234649618]).

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The terms of the new agreement include the development of an additional six targeted alpha therapeutics candidates, now representing a total of ten potential programs between the two companies. Molecular Partners will lead development of the additional six programs, subject to a royalty arrangement, and include an option for Orano Med to move two of the six programs into a 50/50 co-development where Orano Med will hold commercialization rights.

In January 2024, Molecular Partners and Orano Med entered into an initial agreement to co-develop four programs. equally sharing costs for preclinical and clinical development and profit from commercialized products. Molecular Partners holds commercialization rights for the first program, MP0712, a DLL3-targeted radio-DARPin, which is expected to move into first-in-human studies in 2025, pending regulatory clearance. Molecular Partners will also hold commercialization rights to the second program, targeting mesothelin, and Orano Med to programs three and four.

The partnership combines Molecular Partners’ unique and innovative Radio-DARPin Platform with Orano Med’s 212Pb supply, research and clinical development capabilities. Both groups have been working closely together over the past years, reducing drug candidate cycle times and enabling the generation of more drug candidates to novel targets, thereby pushing the boundaries of what is presently achievable by other technologies.

"We are excited to expand this relationship with Orano Med, representing the bold ambition and high synergy of both groups to build the largest radiotherapy pipeline in our space today. Both groups, having worked together over the past year, realize the unique potential of the other, and we have confidence in our abilities to provide novel and innovative targets for the delivery of radioactive isotopes, pushing the boundaries of what is presently targetable by other technologies," said Patrick Amstutz, Ph.D., CEO of Molecular Partners.

"The expansion of our collaboration with Molecular Partners underscores the strength and efficiency of our combined approach. Together, we have established a platform capable of significantly reducing development timelines for lead-212-based Radio-DARPin drug candidates. This partnership exemplifies how strategic synergies can drive innovation and accelerate the delivery of next-generation targeted alpha therapies to patients, and further diversifies vectorization technology in Orano Med’s pipeline," said Arnaud Lesegretain, CEO of Orano Med.

Financial terms of the agreement are not disclosed. Molecular Partners expects no immediate impact on its financial forecast for the fiscal year 2025 from the expansion of the co-development agreement and maintains its funding guidance into 2027.

On January 12, 2025 Biohaven Ltd. (NYSE: BHVN) and Merus N.V. (Nasdaq:MRUS), reported a research collaboration and license agreement to co-develop three novel bispecific antibody drug conjugates (ADCs), leveraging Merus’ leading Biclonics technology platform, and Biohaven’s next-generation ADC conjugation and payload platform technologies (Press release, Merus, JAN 12, 2025, View Source [SID1234649617]).

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Under the terms of the agreement, Biohaven is responsible for the preclinical ADC generation of three Merus bispecific antibodies under mutually agreed research plans. The agreement includes two Merus bispecific programs generated using the Biclonics platform, and one program under preclinical research by Merus. Each program is subject to mutual agreement for advancement to further development, with the parties then sharing subsequent external development costs and commercialization, if advanced.

"We’re excited to collaborate with Biohaven, leveraging their broad range of linker/payload and conjugation technologies, and expertise with the research and development of ADCs, to rapidly advance bispecific antibody candidate ADCs based on the Merus Biclonics platform," said Peter B. Silverman, Chief Operating Officer of Merus. "We believe that the combination of our Biclonics technology, validated by the recent FDA approval of Bizengri and continued clinical success with petosemtamab, together with the Biohaven suite of ADC technologies, has the potential to generate new and differentiated bispecific therapies with greater potency and selectivity over currently available monoclonal ADC approaches."

"We believe this collaboration with Merus will accelerate our ability to create highly differentiated multispecific ADCs, leveraging Biohaven’s innovative conjugation and payload technologies to deliver optimized ADCs with the potential to significantly benefit patients across various cancer types through an enhanced efficacy and safety profile," added Brian Lestini, President, Oncology of Biohaven.

Pursuant to the transaction, Merus will receive an upfront payment and license fee at ADC candidate nomination of the first program, with Merus to assume the preclinical bispecific antibody generation cost, and Biohaven to assume the preclinical ADC generation cost. Thereafter, upon mutual agreement to advance each program, the parties plan to share further development and commercialization costs.

On January 12, 2025 Exelixis, Inc. (Nasdaq: EXEL) reported its preliminary unaudited financial results for the fiscal year 2024, provided financial guidance for fiscal year 2025 and delivered an update on its business (Press release, Exelixis, JAN 12, 2025, View Source [SID1234649616]). Exelixis anticipates 2025 will be a year of clinical and regulatory execution and continued growth for its cabozantinib franchise, as well as multiple data readouts for zanzalintinib and across its diversified pipeline of small molecules and biotherapeutics with the potential to improve standards of care for patients with cancer.

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Preliminary Fiscal Year 2024 Financial Results & 2025 Financial Guidance

Exelixis is providing the following preliminary unaudited 2024 financial results and financial guidance for 2025. Net product and total revenues guidance do not currently reflect any revenues resulting from a potential U.S. regulatory approval and commercial launch of CABOMETYX (cabozantinib) for the treatment of patients with previously treated advanced neuroendocrine tumors (NET). The U.S. Food and Drug Administration (FDA) is currently reviewing Exelixis’ supplemental New Drug Application (sNDA) for this proposed indication, with a Prescription Drug User Fee Act (PDUFA) target action date of April 3, 2025.

Fiscal Year 2024

Fiscal Year 2025 Guidance

Total revenues

~ $2.165 billion

$2.15 billion – $2.25 billion

Net product revenues

~ $1.805 billion

$1.95 billion – $2.05 billion(1)

Cost of goods sold

~ 4.2%

4% – 5% of net product revenues

Research and development expenses

~ $910 million(2)

$925 million – $975 million(3)

Selling, general and administrative expenses

~ $495 million(4)

$475 million – $525 million(5)

Effective tax rate

n/a(6)

21% – 23%

Ending cash and marketable securities(7)

~ $1.75 billion

n/p

(1)

Exelixis’ 2025 net product revenues guidance range includes impact of a U.S. wholesale acquisition cost increase of 2.8% for CABOMETYX effective Jan. 1, 2025.

(2)

Includes $30.7 million of non-cash stock-based compensation expense.

(3)

Includes $40.0 million of non-cash stock-based compensation expense.

(4)

Includes $63.2 million of non-cash stock-based compensation expense.

(5)

Includes $60.0 million of non-cash stock-based compensation expense.

(6)

Preliminary results not yet available.

(7)

Cash and marketable securities are composed of cash, cash equivalents and marketable securities. Fiscal year 2025 guidance not provided (n/p).

The preliminary 2024 financial information presented in this press release has not been audited and is subject to change. The complete Exelixis Fourth Quarter and Fiscal Year 2024 Financial Results are planned for release after market on Tuesday, February 11, 2025.

"Entering 2025, Exelixis stands at an inflection point as we work toward our goal of building a multi-product, multi-franchise oncology business," said Michael M. Morrissey, Ph.D., President & CEO, Exelixis. "Exelixis had a very successful 2024 highlighted by strong commercial and financial performance, the favorable ruling on our cabozantinib patent litigation, accelerating progress with the zanzalintinib pivotal trial program and establishing our zanzalintinib clinical development collaboration with Merck. We’re carrying that momentum into the new year as we seek to grow cabozantinib franchise revenues, accelerate and expand our zanzalintinib pivotal development program, and advance our diversified therapeutic pipeline of small molecules and biotherapeutics."

Dr. Morrissey continued: "We expect 2025 to be a year of regulatory, clinical and commercial execution as we work toward a potential regulatory approval and launch for cabozantinib in neuroendocrine tumors and prepare for multiple zanzalintinib and pipeline data readouts throughout the year. As cabozantinib’s commercial success drives the business forward in the near-term, we’re excited by zanzalintinib’s potential to surpass cabozantinib’s scope and scale in the coming years and to become an important component of our mid- and long-term revenue growth. We’re also optimizing our earlier stage pipeline, rapidly profiling compounds and advancing only those with the highest probability of success into full development. We look forward to providing more detailed updates on our pipeline progress at an R&D Day later this year. Finally, we’ll maintain our balanced approach to capital allocation, leveraging our strong balance sheet to execute on business development opportunities within the GU and GI oncology space, while using free cash flows to fund our stock repurchase program and return capital to shareholders."

Corporate Updates

Stock Repurchase Program Update. In August 2024, 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 the end of fiscal year 2024, Exelixis has repurchased $205.6 million of the company’s common stock, at an average price of $33.62 per share.

Anticipated Cabozantinib Milestones

Potential Label Expansion and Commercial Launch into NET. Exelixis is preparing for the potential commercial launch of CABOMETYX for the treatment of patients with previously treated advanced NET following the FDA’s acceptance of its sNDA and assignment of a PDUFA target action date of April 3, 2025. In January 2025, the FDA notified Exelixis that its sNDA will no longer be the subject of discussion at an Oncologic Drugs Advisory Committee meeting. The regulatory filing was based on positive results from the phase 3 CABINET pivotal trial 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. CABINET met its primary endpoint, demonstrating statistically significant and clinically meaningful improvements in progression-free survival (PFS) for patients treated with cabozantinib as compared to placebo in both its pancreatic NET (pNET) and extra-pancreatic NET (epNET) cohorts. Final results from the trial were subsequently presented at the 2024 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress and published in The New England Journal of Medicine. In January 2025, the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology for NET were updated to include cabozantinib as category 1 for certain types of NET following specific treatments, and as a category 2A preferred regimen for several other forms of advanced NET, depending on site of origin and grade. A subgroup analysis from CABINET detailing the experience of patients with advanced gastrointestinal (GI) NET will also be presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) GI Cancers Symposium (ASCO GI 2025) later this month. Exelixis’ partner Ipsen anticipates a decision from the European Medicines Agency on its Marketing Authorization Application for its own proposed NET label expansion in the EU for cabozantinib in 2025. While Exelixis prioritizes supporting the FDA’s ongoing review of its proposed NET indication, the company will continue to evaluate the timing of its potential regulatory filing for cabozantinib in metastatic castration-resistant prostate cancer based on the phase 3 CONTACT-02 pivotal study.

Anticipated Development Milestones

Expansion and Acceleration of the Zanzalintinib Pivotal Trial Program. Zanzalintinib is a third-generation tyrosine kinase inhibitor (TKI) that Exelixis believes can become the vascular endothelial growth factor receptor TKI of choice as the solid tumor therapeutic landscapes continue to evolve. The zanzalintinib pivotal development program currently consists of six ongoing or planned pivotal trials, with additional studies to be announced in 2025 and beyond:

STELLAR-303 is evaluating zanzalintinib in combination with atezolizumab compared with regorafenib in patients with metastatic, refractory non-microsatellite instability-high or non-mismatch repair-deficient colorectal cancer (CRC). The primary endpoint in the study is overall survival (OS) in the patients without liver metastases (NLM). If OS is positive in the NLM population, the study will evaluate OS in the intent-to-treat population that includes patients with and without liver metastases. The study completed enrollment in the third quarter of 2024, and preliminary results are expected in the second half of 2025, dependent on study event rates.
STELLAR-304 is evaluating zanzalintinib in combination with nivolumab versus sunitinib in previously untreated patients with advanced non-clear cell renal cell carcinoma. The primary endpoints in the trial are PFS and objective response rate. Based on current enrollment status in the trial, the primary endpoint of PFS is expected to be available in the second half of 2025, dependent on study event rates.
STELLAR-305 is evaluating zanzalintinib in combination with pembrolizumab versus pembrolizumab alone in patients with previously untreated PD-L1-positive recurrent or metastatic squamous cell carcinoma of the head and neck. The study was designed to enroll approximately 250 eligible patients in the phase 2 portion of the trial to be randomly assigned to zanzalintinib in combination with pembrolizumab or pembrolizumab alone to evaluate the activity of the combination therapy. Data from the phase 2 portion are expected be available in the second half of 2025, which would inform whether the data support expansion into the phase 3 portion of the trial, during which an additional 350 patients would be randomized for a total of 600 patients. The primary endpoints in the study are PFS and OS.
Exelixis also expects to initiate STELLAR-311, a 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.
Additionally, as part of Exelixis’ clinical development collaboration with Merck, two pivotal renal cell carcinoma (RCC) studies are planned for 2025. The companies will provide further details on these trials closer to their initiation.
Earlier Stage Zanzalintinib Data Readouts Expected This Year. Exelixis anticipates initial clinical data readouts from zanzalintinib’s phase 1b/2 STELLAR-001 and STELLAR-002 clinical studies in the first half of 2025, including data from CRC and RCC cohorts. STELLAR-001 and -002 are evaluating zanzalintinib as a monotherapy and in potentially best-in-class combination regimens across various tumor types. In the nearest term, at ASCO (Free ASCO Whitepaper) GI 2025 later this month, investigators will present preliminary results from a randomized expansion cohort of STELLAR-001 designed to assess the contribution of atezolizumab to zanzalintinib in patients with previously treated metastatic CRC.

Advance XL309 Phase 1 Program in PARP Inhibitor Refractory Setting and Beyond. XL309, Exelixis’ potentially best-in-class small molecule inhibitor of USP1, is currently being evaluated in a phase 1 study as a single agent and in combination with olaparib, a PARP1/2 inhibitor, in patients with advanced solid tumors. Enrollment in the dose escalation cohorts for XL309 monotherapy and olaparib combination are ongoing. The mechanism of action of XL309 and its potential to combine with PARP-inhibitors (PARPi) provide optionality for a robust development program in a variety of solid tumors. Exelixis’ clinical development plans for XL309 include its development as a potential therapy for tumors that have become refractory to PARPi therapy, including forms of ovarian, breast and prostate cancers, pursuing potential PARPi combinations, and moving beyond the PARPi market into new areas. Exelixis plans to present data from the XL309 program at a scientific meeting in 2025.

Progress of Phase 1 Clinical Trials for XB010 and XL495. Exelixis initiated clinical development of its XB010 and XL495 pipeline programs in 2024. The company plans to rapidly profile each compound to determine if early clinical data support further advancement toward full development. XB010 is an antibody-drug conjugate (ADC) consisting of a monomethyl auristatin E payload conjugated to a monoclonal antibody targeting the tumor antigen 5T4 and is the first custom ADC generated through Exelixis’ biotherapeutics collaboration network. The first-in-human, global phase 1 trial of XB010 is evaluating the compound in patients with locally advanced or metastatic solid tumors. The dose-escalation stage of the 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. XL495 is a novel, potent, small molecule inhibitor of PKMYT1. The first-in-human phase 1 clinical trial of XL495 is evaluating the compound in patients with advanced solid tumors; the dose-escalation stage of the 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. Exelixis plans to present preclinical data from the XL495 program at a scientific meeting in 2025.

Anticipated Discovery Milestones

Three Potential Investigational New Drug (IND) Applications in 2025. Exelixis anticipates advancing three biotherapeutics programs into clinical development this year, including the XB628 PD-L1-NKG2A bispecific antibody, XB064 ILT-2 monoclonal antibody and XB371 TF-topoisomerase I inhibitor ADC. The company expects to file the IND applications for these compounds in 2025 if preclinical data continue to be supportive. Exelixis plans to present preclinical data from one or more of these programs at a scientific meeting in 2025.

Presentation and Webcast

Exelixis President and Chief Executive Officer Michael M. Morrissey, Ph.D., will provide a corporate overview and discuss the company’s preliminary fiscal year 2024 financial results, 2025 financial guidance and key priorities and milestones for 2025 during the company’s presentation at the 43rd Annual J.P. Morgan Healthcare Conference beginning at 5:15 p.m. PT / 8:15 p.m. ET on Monday, January 13, 2025.

To access the webcast link, log onto www.exelixis.com and proceed to the Event Calendar page under the Investors & News heading. A replay will also be available at the same location for at least 30 days.