On June 22, 2025 Exelixis, Inc. (Nasdaq: EXEL) reported positive topline results from the STELLAR-303 phase 3 pivotal trial in which zanzalintinib in combination with atezolizumab (Tecentriq) demonstrated a statistically significant improvement in overall survival (OS) versus regorafenib in the intent-to-treat (ITT) population of patients with previously treated non-microsatellite instability (MSI)-high metastatic colorectal cancer (CRC) (Press release, Exelixis, JUN 22, 2025, View Source [SID1234654040]). These topline findings are from the final analysis conducted by the Independent Data Monitoring Committee of one of the dual primary endpoints of the STELLAR-303 phase 3 trial. The trial will proceed to the planned final analysis for the other dual primary endpoint of OS in patients without liver metastases (non-liver metastases, NLM).

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The safety profiles of zanzalintinib in combination with atezolizumab and of regorafenib were generally consistent with what has been previously observed, and no new safety signals were identified.

The ITT population consisted of all randomized patients, regardless of the presence of liver metastases. The NLM subgroup consisted of patients who did not have active liver metastases at baseline as determined by investigator assessment.

"The STELLAR-303 results, which showed a survival benefit with the combination of zanzalintinib and atezolizumab versus regorafenib across all randomized patients with previously treated metastatic colorectal cancer, marks an important first milestone for our zanzalintinib pivotal development program," said Amy Peterson, M.D., Executive Vice President, Product Development & Medical Affairs, and Chief Medical Officer, Exelixis. "We look forward to discussing the findings with regulatory authorities and presenting the detailed results at an upcoming medical conference."

Secondary endpoints of STELLAR-303 include progression-free survival, objective response rate and duration of response in the ITT population and in the NLM subgroup of patients. Exelixis plans to submit detailed results of STELLAR-303 for presentation at an upcoming medical conference.

About STELLAR-303
STELLAR-303 (NCT05425940) is a global, multicenter, randomized, phase 3, open-label study that randomized 901 patients 1:1 to either zanzalintinib (100 mg) in combination with atezolizumab or regorafenib. The study includes patients with previously treated non-MSI-high metastatic CRC. The dual primary endpoints of the study are OS in the ITT population and in the NLM subgroup of patients. Presence of liver metastases at baseline for all enrolled patients was determined by investigator assessment. Secondary endpoints include progression-free survival, objective response rate and duration of response in the ITT population and in the NLM subgroup of patients. More information about the trial is available at ClinicalTrials.gov.

About Zanzalintinib
Zanzalintinib is a third-generation oral tyrosine kinase inhibitor that inhibits the activity of receptor tyrosine kinases implicated in cancer growth and spread, including VEGF receptors, MET, AXL and MER. These receptor tyrosine kinases are involved in both normal cellular function and in pathologic processes such as oncogenesis, metastasis, tumor angiogenesis and resistance to multiple therapies, including immune checkpoint inhibitors. With zanzalintinib, Exelixis sought to build upon its extensive experience with the target profile of cabozantinib, the company’s flagship medicine, while improving key characteristics, including pharmacokinetic half-life. Zanzalintinib is currently being developed for the treatment of advanced solid tumors, including colorectal cancer, kidney cancer, head and neck cancer and neuroendocrine tumors.

Zanzalintinib is an investigational agent that is not approved for any use and is the subject of ongoing clinical trials.

About CRC
CRC is the third most common cancer and the second leading cause of cancer-related deaths in the U.S.1 Approximately 154,000 new cases will be diagnosed in the U.S. with around 53,000 expected deaths from the disease in 2025.1 CRC is most frequently diagnosed among people aged 65-74 and is more common in men and in people of non-Hispanic American Indian/Alaska Native descent.2 Nearly a quarter of CRC cases are diagnosed at the metastatic stage, at which point the five-year survival rate is just 16.2%.2 The liver is the most common site for CRC metastasis. Liver metastases significantly impact survival, with a median five-year survival rate of less than 14% when treated with palliative chemotherapy.

On June 22, 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") 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 debut of MP0726, its Radio-DARPin candidate targeting mesothelin (MSLN) and will present preclinical data in an oral presentation at the 2025 Annual Meeting of the Society of Nuclear Medicine and Molecular Imaging (SNMMI), taking place June 21-24 in New Orleans, LA, USA (Press release, Molecular Partners, JUN 22, 2025, View Source [SID1234654039]).

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The oral presentation outlines encouraging early preclinical proof-of-concept data showing that MP0726 binds with high affinity and selectivity to the membrane-proximal domain of MSLN without being impacted by shed MSLN. In vivo results in a MSLN tumor model show a favorable biodistribution with substantial uptake of the Radio-DARPin in MSLN-positive tumors, while other organs showed limited accumulation. At 24 hours post injection, tumor accumulation was up to 34%, resulting in a tumor to kidney ratio of up to 4.5.

MP0726 leverages the unique properties of DARPins to selectively bind membrane-bound MSLN, a promising target for ovarian cancer due to its differentiated expression profiles – high in tumor, and lower in healthy tissues. High levels of shed MSLN can act as a decoy receptor and have historically hampered the development of MSLN-targeted therapeutics. MP0726 is being co-developed under Molecular Partners’ strategic partnership with Orano Med.

"Our collaboration with Molecular Partners has been delivering substantial progress in a short time, reflecting the skills, passion and strong complementarity of our teams. This progress highlights the effectiveness of our joint R&D efforts, enabling us to identify and advance differentiated clinical candidates that address important unmet medical needs. With its world-class R&D capabilities, the ownership of a virtually unlimited supply of the starting isotope, and fully-integrated manufacturing supply chain, Orano Med is uniquely positioned to support the development of these important potential new medicines", said Arnaud Lesegretain, CEO of Orano Med.

"We are proud to advance our second Radio-DARPin candidate into development, together with our partner Orano Med, for patients with MSLN expressing cancers. The promising preclinical data indicate a favorable biodistribution profile and highlight the unique approach to targeting MSLN with MP0726," said Patrick Amstutz, Ph.D., CEO of Molecular Partners.

MP0726 represents the second Radio-DARPin program to move into pre-clinical development. The first Radio-DARPin program, MP0712 targeting DLL3, is on track to dosing the 1st patient in a Phase 1 study in the US in the second half of 2025.

Details of the presentation:

Preclinical characterization of a Lead-212 Radio-DARPin Therapeutic to selectively target membrane-bound mesothelin in solid tumors
Date & Time: 24 June 2025; 2:50-3:00 pm CST
Session: SS38 Radiopharmaceutical Oncology – Preclinical and Early Phase (2:30-3:45 pm CST)

About 212Pb-based Radio-DARPins
Molecular Partners’ Radio-DARPin platform is being developed to provide a unique and innovative delivery system for radioactive payloads, with exquisite targeting capabilities of DARPins combined with the optimally balanced safety and tumor killing of 212Pb. DARPins are ideal vectors for efficient delivery of therapeutic radionuclides to solid tumors, while overcoming some historic limitations of radioligand therapy approaches, thanks to their small size as well as high specificity and affinity. Molecular Partners and Orano Med are developing targeted alpha radio-therapeutics against up to ten targets, including the tumor-associated protein Delta-like ligand 3 (DLL3) and mesothelin (MSLN).

On June 20, 2025, Alaunos Therapeutics, Inc. (the "Company") reported to have entered in a securities purchase agreement (the "Securities Purchase Agreement") with certain purchasers identified therein, pursuant to which the Company agreed to issue and sell (i) 338,725 shares of common stock (the "Shares"), par value $0.001 per share of the Company ("Common Stock"), at a purchase price of $3.36 per share; and (ii) 271,674 pre-funded warrants to purchase Common Stock, at a purchase price of $3.359 per share, in a registered direct offering (the "Offering") (Filing, 8-K, Alaunos Therapeutics, JUN 20, 2025, View Source [SID1234654140]).

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The Offering was made pursuant to the Company’s currently effective shelf registration statement on Form S-3 (Registration File No. 333- 266841), which was initially filed with the U.S. Securities and Exchange Commission (the "Commission") on August 12, 2022, as amended by Amendment No. 1 thereto, which was filed with the Commission on August 31, 2025, and was declared effective on September 7, 2022.

The Offering closed on June 24, 2025. The Company intends to use the net proceeds from the Offering for general corporate purposes, which may include among other things, capital expenditures and working capital.

The Securities Purchase Agreement contains customary representations, warranties, covenants, and other agreements by the Company. The foregoing description of the Securities Purchase Agreement is only a summary and is qualified in its entirety by reference to the full text of the Securities Purchase Agreement, which is filed as Exhibit 10.1 to this Current Report on Form 8-K and incorporated by reference in this Item 1.01.

A copy of the opinion and consent of Norton Rose Fulbright US LLP, as legal counsel to the Company, regarding the legality of the issuance and sale of the Offering Shares is attached hereto as Exhibit 5.1 and Exhibit 23.1 to this Current Report on Form 8-K.

This Current Report on Form 8-K is not an offer to sell any securities of the Company and is not soliciting an offer to buy such securities in any state where such offer and sale is not permitted.

On June 20, 2025, Aptose Biosciences Inc., as borrower (the "Company"), reported that it had entered into a loan agreement (the "Loan Agreement") with Hanmi Pharmaceutical Co. Ltd., as lender ("Hanmi") (Filing, 8-K, Aptose Biosciences, JUN 20, 2025, View Source [SID1234654132]). The Loan Agreement is an uncommitted facility for up to US$8.5 million (the "Facility"), administered through multiple advances for the purpose of continued clinical development of a Tuspetinib ("TUS") based triple drug frontline therapy to treat patients with newly diagnosed acute myeloid leukemia (AML), accounts payable with respect of the Company’s TUS related business operations, and general corporate purposes reasonably related to the Company’s TUS related business operations.

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The Facility may be advanced in one or more (but not more than five (5) advances) until December 31, 2025. The Facility is a non-revolving facility, and amounts repaid thereunder may not be reborrowed. No single advance shall be for an amount in excess of US$2,500,000.

The aggregate principal amount of all advances and all accrued and unpaid interest and fees together with all other obligations under the Loan Agreement will be repayable by the Company in full on August 31, 2028. Any unpaid principal amount with respect to each advance shall accrue interest a six percent (6%) per annum.

The proceeds from borrowings under the Loan Agreement will be used by the Company to fund its: (a) TUS related business operations, (b) accounts payable with respect of the Company’s TUS related business operations, and (c) general corporate purposes reasonably related to the Company’s TUS related business operations, in each case, unless the Company has obtained the prior written approval of Hanmi.

The Loan Agreement also contains customary affirmative and negative covenants with respect to the Company, including, among other things, compliance with laws, no change of business, no merger and maintenance of corporate existence, maintenance of insurance, restrictions on the incurrence of loans and guarantees, and other customary covenants. These covenants are subject to a number of limitations and exceptions as provided in the Loan Agreement.

The Company’s obligations under the Loan Agreement are secured by a first ranking security interest over all present and after acquired personal property of the Company and unlimited guarantees by, and first ranking security over all present and after acquired personal property of each of Aptose’s subsidiaries.

Additionally, the Loan Agreement contains customary events of default, insolvency, cessation of production, material adverse effect as well as remedies for credit facilities of this nature.

The description of the Loan Agreement contained in this Item 1.01 is qualified in its entirety by reference to the complete text of the Loan Agreement, a copy of which is filed herewith as Exhibit 10.1, to this Current Report on Form 8-K.

On June 20, 2025 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported results from the phase III SUNMO [NCT05171647] study showing Lunsumio (mosunetuzumab) administered subcutaneously in combination with Polivy (polatuzumab vedotin) demonstrated a clinically meaningful and statistically significant improvement in its primary endpoints of progression-free survival (PFS) and objective response rate (ORR) compared to MabThera/Rituxan (rituximab), gemcitabine and oxaliplatin (R-GemOx), in people with relapsed or refractory (R/R) large B-cell lymphoma (LBCL) who are not eligible for transplant (Press release, Hoffmann-La Roche, JUN 20, 2025, View Source [SID1234654041]). Primary analysis data were featured at the 18th International Conference on Malignant Lymphoma as a late-breaking oral presentation.

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Results from the SUNMO study will be submitted to global health authorities, including the US Food and Drug Administration. The National Comprehensive Cancer Network (NCCN) has recently added Lunsumio and Polivy to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) as a category 2A recommendation for the treatment of people with second-line (2L) diffuse large B-cell lymphoma (DLBCL) who are not intended to proceed to transplant.†2

"Lunsumio and Polivy represent the first combination of a bispecific antibody and antibody-drug conjugate, which could avoid chemotherapy and potentially provide an alternative option for some patients with relapsed or refractory LBCL," said Levi Garraway, MD, PhD, Roche’s Chief Medical Officer and Head of Global Product Development. "We are also encouraged by the favourable safety profile and potential for outpatient use of this regimen, which may suit diverse patient and healthcare system needs."

At a median follow-up of 23.2 months, the Lunsumio and Polivy combination demonstrated a 59% reduction in risk of disease progression or death compared to R-GemOx (hazard ratio [HR] 0.41, 95% confidence interval [CI]: 0.28–0.61; p<0.0001).1 Median PFS was three times longer with Lunsumio and Polivy at 11.5 months (95% CI: 5.6-17.6), compared to 3.8 months for R-GemOx (95% CI: 2.9-4.1) and 12-month PFS was more than doubled at 48.5% (95% CI: 39.6-57.4) vs.17.8% (95% CI: 5.4-30.3), respectively. This PFS benefit was consistent across subgroups, including in high-risk patients with primary refractory disease (HR 0.46, 95% CI: 0.29–0.72).1 At the interim analysis, overall survival (OS) data were not yet mature. OS numerically favoured the Lunsumio and Polivy combination with a median of 18.7 months (95% CI: 14.1–not evaluable [NE]) compared to 13.6 months for R-GemOx (95% CI: 9.9–NE; HR 0.80; 95% CI: 0.54 – 1.20).1

"There remains a clear need for effective and well-tolerated treatments for people with this difficult-to-treat disease," said Jason Westin, Professor of Lymphoma and Director of Lymphoma Clinical Research, The University of Texas, MD Anderson Cancer Center. "If approved, this off-the-shelf treatment combination of mosunetuzumab and polatuzumab vedotin could be administered over a fixed period of time, without mandatory hospitalisation or traditional chemotherapy, which could provide a meaningful option for patients with relapsed or refractory LBCL."

In the Lunsumio and Polivy arm, 30% more patients achieved an objective response (70.3%, 95% CI: 61.9-77.8) compared to R-GemOx (40.0%; 95% CI: 28.5-52.4), and the complete response rate was doubled at 51.4% (95% CI: 42.8-60.0) vs. 24.3% (95% CI: 14.8-36.0).1 Nearly 75% of patients with a complete response were still in remission after one year (72.6%; 95% CI: 61.4-83.8) compared to 44.1% for R-GemOx (95% CI: 13.2-74.9).1

The safety profile of the Lunsumio and Polivy combination was consistent with the known profiles of the individual study medicines, potentially allowing use across outpatient and community settings.1 The incidence of cytokine release syndrome events (CRS) in the Lunsumio plus Polivy arm was low, occurring in one in four patients, with less than 5% of patients experiencing Grade (Gr) 2 or 3 CRS events.1 No immune effector cell-associated neurotoxicity syndrome events were reported. Rates of Gr3–4 (58.5% vs. 57.8%) and Gr5 (5.2% vs. 6.3%) adverse events (AEs) were similar between the combination and R-GemOx, with fewer AEs leading to treatment discontinuation in the Lunsumio and Polivy arm (2.2% vs. 4.7%).1

High-dose chemotherapy followed by stem-cell transplant has traditionally been the standard 2L treatment for people with R/R LBCL.3 While 2L therapies have advanced, DLBCL can progress rapidly and many people are not candidates for, cannot tolerate, or do not have access to latest therapies.2,4 There is an urgent need for treatments that are rapidly available upon a diagnosis of relapse, that can manage the disease and improve long-term outcomes.

Roche’s lymphoma portfolio is one of the broadest in the industry, providing a unique and much-needed opportunity to combine regimens with different and complementary mechanisms of action. We are exploring our CD20xCD3 bispecifics, Lunsumio and Columvi (glofitamab), alongside Polivy to move one step closer towards our goal of improving the lives of as many patients with lymphomas as possible. This includes the phase III STARGLO study [NCT04408638] evaluating the efficacy and safety of Columvi in combination with GemOx versus R-GemOx alone in patients with R/R DLBCL who have received at least one prior line of therapy and who are not candidates for autologous stem cell transplant, or who have received two or more prior lines of therapy.

Lunsumio is already approved for people with R/R follicular lymphoma after two or more lines of therapy in more than 60 countries worldwide. Polivy in combination with MabThera/Rituxan, cyclophosphamide, doxorubicin and prednisone is approved for people with previously untreated DLBCL in more than 100 countries worldwide and in combination with bendamustine and MabThera/Rituxan for R/R DLBCL in more than 90 countries worldwide.

About the SUNMO study
The SUNMO [NCT05171647] study is an international, multi-centre, randomised phase III trial evaluating the efficacy and safety of subcutaneously administered Lunsmio (mosunetuzumab) in combination with intravenous Polivy (polatuzumab vedotin) compared to MabThera/Rituxan (rituximab), gemcitabine and oxaliplatin (R-GemOx), in people with relapsed or refractory (R/R) large B-cell lymphoma (LBCL) who are not eligible for autologous stem cell transplant. Outcome measures include progression-free survival and objective response rate (dual primary endpoints), overall survival, duration of objective response, complete response rate, duration of complete response, safety and tolerability, and patient-reported outcomes.

About Lunsumio (mosunetuzumab)
Lunsumio is a first-in-class CD20xCD3 T-cell-engaging bispecific antibody designed to target CD3 on the surface of T cells and CD20 on the surface of B cells. This dual-targeting activates and redirects a patient’s existing T cells to engage and eliminate target B cells by releasing cytotoxic proteins into the B cells. A robust clinical development programme for Lunsumio is ongoing, investigating the molecule as a monotherapy and in combination with other medicines, for the treatment of people with B-cell non-Hodgkin lymphomas, including follicular lymphoma, diffuse large B-cell lymphoma, and other indications.

About Polivy (polatuzumab vedotin)
Polivy is a first-in-class anti-CD79b antibody-drug conjugate (ADC). The CD79b protein is expressed in the majority of B cells, an immune cell impacted in some types of non-Hodgkin lymphoma (NHL), making it a promising target for the development of new therapies. Polivy binds to cancer cells such as those expressing CD79b and destroys these B cells through the delivery of an anti-cancer agent, which is thought to minimise the effects on normal cells. Polivy is being developed by Roche using Pfizer ADC technology and is currently being investigated for the treatment of several types of NHL.

About large B-cell lymphoma (LBCL)
Large B-cell lymphomas (LBCL), composed predominantly of diffuse large B-cell lymphoma (DLBCL), are the most common type of non-Hodgkin lymphoma (NHL) that affect B-cell lymphocytes, a type of white blood cells. DLBCL is the most common form of aggressive NHL and makes up about 80% of LBCLs. While it can arise in lymph nodes, it can also occur in organs outside of the lymphatic system. Approximately 160,000 people worldwide are diagnosed with DLBCL each year, with comparable incidence rates across regions. Medical practices, including pathological classification, diagnosis, staging, initial treatment and relapse management, are similarly approached worldwide. While it is generally responsive to treatment in the frontline, as many as 40% of people will relapse or have refractory disease, at which time salvage therapy options are limited and survival is short. Improving treatments earlier in the course of the disease and providing much needed alternative options could help to improve long-term outcomes.