On March 18, 2025 Tuhura Biosciences presented its corporate presentation (Presentation, TuHURA Biosciences, MAR 18, 2025, View Source [SID1234651222]).

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On March 18, 2025 Kronos Bio, Inc. (Nasdaq: KRON), a biopharmaceutical company, reported fourth quarter and full year 2024 financial results (Press release, Kronos Bio, MAR 18, 2025, View Source [SID1234651223]).

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Fourth Quarter and Full Year 2024 Financial Results

▪Cash, cash equivalents and investments: Cash, cash equivalents and investments as of December 31, 2024, were $112.4 million.

▪R&D Expenses: Research and development expenses were $8.4 million for the fourth quarter of 2024, which includes non-cash stock-based compensation expense of $0.7 million. For the full year of 2024, research and development expenses were $48.7 million, which includes non-cash stock-based compensation expense of $3.4 million.

▪G&A Expenses: General and administrative expenses were $4.9 million for the fourth quarter of 2024, which includes non-cash stock-based compensation expense of $1.0 million. For the full year of 2024, general and administrative expenses were $24.6 million, which includes non-cash stock-based compensation expense of $5.8 million.

▪Impairment of long-lived assets and restructuring: Impairment of long-lived assets and restructuring charges were $16.1 million for the fourth quarter of 2024, which includes non-cash impairment charges of $11.6 million and non-cash stock-based compensation expense of $0.5 million. For the full year of 2024, Impairment of long-lived assets and restructuring charges were $29.5 million, which includes non-cash impairment charges of $18.7 million and non-cash stock-based compensation expense of $4.9 million.

▪Net loss: Net loss for the fourth quarter of 2024 was $25.8 million, or $0.43 per share, including non-cash stock-based compensation expense of $2.2 million. Net loss for the full-year 2024 was $86.1 million, or $1.43 per share, including non-cash stock-based compensation expense of $14.1 million.

On March 18, 2025 Oncorena reported that the FDA has approved the Company’s IND application to initiate the Phase I/II study Oncorella-1: A Phase 1/2, open label, single arm study on safety, tolerability and anti-tumor efficacy of orellanine treatment in patients with metastatic clear-cell or papillary renal cell carcinoma (NCT05287945, ONC001-CL-001) (Press release, Oncorena, MAR 18, 2025, View Source [SID1234651241]).

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In the study Oncorella-1, up to 75 patients with severe metastatic renal cancer requiring dialysis will be enrolled. These patients have exhausted their treatment options and ONC175 represents a potentially new first-in-class treatment for patients with urgent unmet medical need.

The study is currently being conducted at Karolinska University Hospital in Stockholm, Sweden.

Börje Haraldsson, CEO & co-founder of Oncorena comments:

"This approval brings us closer to being able to evaluate the potential for this novel treatment in patients in desperate need for new and better options. We are excited to start the first US site, MD Andersson in Houston, Texas, where the study will be led by investigator Professor Nizar Tannir, a world-leading expert in renal cancer."

About ONC175

ONC175 is an investigational drug product under development that contains synthetically produced orellanine as active ingredient. Orellanine is highly specific to the kidney and induces irreversible renal failure. It is clinically well-known that orellanine does not affect organs other than the kidneys.

In pioneering preclinical studies ONC175 demonstrated a powerful and highly organ-specific mode of action capable of eradicating human metastatic renal cancer cells. The primary goal is to develop ONC175 as a potential curative treatment of metastatic renal cell carcinoma in patients with no remaining kidney function, i.e., patients on dialysis.

About kidney cancer

Approximately 400,000 patients are affected by kidney cancer globally according to the WHO. The disease can often be cured by surgery if detected early, but the prognosis is less favorable if there are metastases. Today, the disease is treated with various types of targeted and immuno-active drugs, that seldom are curative. There is therefore a great and urgent unmet medical need for new, effective and safe drugs.

As previously disclosed in the Aptose Biosciences Inc.’s (the "Company") current report on Form 8-K filed August 30, 2024, the Company and Hanmi Pharmaceutical Co., Ltd. ("Hanmi") reported to have entered into a facility agreement on August 27, 2024 (the "Facility Agreement") whereby Hanmi agreed to loan certain amounts to the Company (the amounts loaned are referred to herein as the "Indebtedness Amount") (Filing, 8-K, Aptose Biosciences, MAR 24, 2025, View Source [SID1234651362]). On March 18, 2025, the Company entered into a debt conversion and interest payment agreement ("Debt Conversion Agreement") with Hanmi pursuant to which the Company and Hanmi agreed to convert $1,513,533.10 of the Indebtedness Amount, into 409,063 common shares (the "Conversion Shares") at $3.70 per share which is the average closing price of the Company’s common shares on Nasdaq for the five trading days immediately prior to entering into the Debt Conversion Agreement which such price being equal to Nasdaq’s "Minimum Price" as defined in Nasdaq’s Listing Rule 5635(d). The Company and Hanmi agreed that without prejudice with respect to interest payments owed to Hanmi as set forth in the Facility Agreement for the period commencing on December 21, 2024 and ending on March 31, 2025 (the "Interest Payments") that the Interest Payments may be made on before the final closing date of the Capital Raise (as defined in the Debt Conversion Agreement) and shall not be considered an event of default under the Facility Agreement is such interest payments are made no later than June 27, 2025. The Debt Conversion Agreement reiterated that failure to pay the Interest Payments would constitute an event of default under the Facility Agreement.

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The Debt Conversion Agreement also provides that additional conversions of Indebtedness Amount will be available in Hanmi’s discretion after the completion of the Capital Raise subject to certain additional conditions, including, but not limited to, Hanmi’s ownership threshold not exceeding 19.99%.

Investor’s Rights Agreement

In connection with the Debt Conversion Agreement, the Company and Hanmi entered into a Second Amended and Restated Investor’s Rights Agreement (the "Investor Rights Agreement"), which amends and restates the Amended and Restated Investor’s Rights Agreement entered by the parties on January 25, 2024. The Investor Rights Agreement provides, among other things, that Hanmi shall benefit from Rule 144 of the U.S. Securities Act of 1933, as amended ("Rule 144"), such as receiving from the Company a written statement that it has complied with the requirements of Rule 144 and other such information that may be reasonably requested by Hanmi so that it may sell its securities pursuant to Rule 144 without registration. So long as Hanmi owns at least 10% of the Company’s issued and outstanding common shares, Hanmi will have the right to designate for employment one or more individuals that are legally able to work in the United States or Canada (each, an "Hanmi Nominee") to a position or positions within the Company in applicable areas based on each Hanmi Nominee’s skills, education and experience. The parties agreed that the Hanmi Nominee shall be subject to the Company’s usual employment rules, practices, policies, evaluation procedures, as amended from time to time and the Company shall retain the right, in its sole discretion, to terminate such Hanmi Nominee’s appointment with the Company for violations of the Company’s employment rules, practices, policies and procedures. The parties also agreed that the Hanmi Nominee shall be entitled to salary, bonus, vacation, incentive payments and bonuses, expenses, allowances and any applicable benefits in amounts and to the extent consistent with employees of the Company serving or having recently served in a similar capacity with the Company with such amounts to be reimbursed to the Company by Hanmi. In the event that a visa or other permit is required to be obtained to permit the Hanmi Nominee to work in the United States or Canada the parties agreed that the Company would use its commercially reasonable efforts to assist the Hanmi Nominee with obtaining such visa or permit. The parties agreed that upon the nomination of the Hanmi Nominee that the parties would enter into a separate service agreement to outline the specific terms and conditions of the Hanmi Nominee’s appointment.

The Investor Rights Agreement also provides for customary demand and piggyback registration rights to Hanmi. Among other things, Hanmi is entitled to four (4) demand registrations where Hanmi can require the Company to register on a registration statement the common shares it has received in prior issuances, including pursuant to the Debt Conversion Agreement, and common shares issuable upon the exercise of the warrants under which Hanmi is entitled to purchase up to an additional 77,972 common shares. Hanmi was also granted piggyback registration rights where if the Company proposes to file a registration statement, Hanmi, at the Company’s own cost and expense can have such common shares included on that registration statement on the same term and conditions as any similar securities of the Company. Further, upon Hanmi’s request, the Company must provide inspection rights for Hanmi to access the Company’s books and records, and to the Company’s management to the extent that such access to management does not materially interfere with the operations of the Company.

The foregoing is only a summary of the Debt Conversion Agreement and Investor’s Rights Agreement, and does not purport to be complete descriptions. The summaries of the Debt Conversion Agreement and Investor’s Rights Agreement are qualified in their entirety by reference to the Debt Conversion Agreement and Investor’s Rights Agreement, which are attached hereto as Exhibit 10.1 and Exhibit 10.2 respectively, and are incorporated herein by reference.

On March 18, 2025 Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high quality medicines for the treatment of oncology, cardiovascular and metabolic, autoimmune, ophthalmology and other major diseases, and HUTCHMED (China) Limited ("HUTCHMED") (Nasdaq/AIM:HCM; HKEX:13), reported that the FRUSICA-2 Phase 2/3 clinical trial evaluating sintilimab in combination with fruquintinib as second-line treatment for locally advanced or metastatic renal cell carcinoma (RCC) in China has met its primary endpoint of progression free survival (PFS) per RECIST 1.1 as assessed by blinded independent central review (BICR) (Press release, Innovent Biologics, MAR 18, 2025, View Source [SID1234651242]).

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The combination of sintilimab and fruquintinib received conditional approval from China’s National Medical Products Administration (NMPA) for the treatment of patients with advanced endometrial cancer with Mismatch Repair proficient (pMMR) tumors that have failed prior systemic therapy and are not candidates for curative surgery or radiation, based on data from the FRUSICA-1 study (NCT03903705).

The FRUSICA-2 study is a randomized, open-label, active-controlled study to evaluate the efficacy and safety of sintilimab in combination with fruquintinib versus axitinib or everolimus monotherapy for the second-line treatment of advanced RCC (NCT05522231). In addition to the primary endpoint PFS, the combination also demonstrated improvements in secondary endpoints, including objective response rate (ORR) and duration of response (DoR). Full results will be submitted for presentation at an upcoming scientific conference.

Prof Dingwei Ye of Fudan University Shanghai Cancer Center and the co-leading Principal Investigator of the FRUSICA-2 study, said: "The rapid advancements in targeted therapies, immunotherapies, and their combination regimens have led to a significant evolution in the treatment landscape for advanced renal cell carcinoma. Targeted therapy remains an indispensable and crucial component in systemic treatment of advanced RCC in China. Optimizing the selection of targeted therapy, either as monotherapy or in combination with immunotherapy, for individual patients is a key focus of clinical interest. The results from the FRUSICA 2 study underscore the potential of the sintilimab and fruquintinib combination to address the pressing medical needs of patients with this challenging disease."

Prof Zhisong He of Peking University First Hospital and the co-leading Principal Investigator of the FRUSICA-2 study, said: "The positive results from this Phase 3 study of the sintilimab and fruquintinib combination represent a significant advancement in the treatment of advanced renal cell carcinoma. We are optimistic about the clinical implications of the findings as we strive to provide more effective treatment options for patients who may not have had adequate responses to previous therapies."

Dr Hui Zhou, Senior Vice President of Innovent, stated: "We are encouraged by the positive results in the FRUSICA-2 clinical trial. These outcomes not only underscore the great potential of the combination therapy of sintilimab and fruquintinib but also bring new hope to previously treated patients with advanced renal cell carcinoma. We look forward to working closely with HUTCHMED to jointly advance the registrational communication of this innovative combo therapy and make it available to patients as soon as possible."

Dr Michael Shi, Head of R&D and Chief Medical Officer of HUTCHMED, stated: "The encouraging results from our study provide clear evidence for the combination of fruquintinib and sintilimab as a viable new treatment option for advanced renal cell carcinoma patients who have progressed on previous therapy. This not only reaffirms our commitment to advancing cancer therapies but also represents an important step forward in addressing unmet medical needs within this patient population. I extend my heartfelt gratitude to the patients and investigators who participated in this research; their contributions have been vital to our success. We look forward to sharing detailed findings with regulatory authorities and progressing toward NDA filings in the coming months."

About Kidney Cancer and RCC

It is estimated that approximately 435,000 new patients were diagnosed with kidney cancer worldwide in 2022.[i] In China, an estimated 74,000 new patients were diagnosed with kidney cancer in 2022.[ii] Approximately 90% of kidney tumors are RCC.

About Sintilimab

Sintilimab, marketed as TYVYT (sintilimab injection) in China, is a PD-1 immunoglobulin G4 monoclonal antibody co-developed by Innovent and Eli Lilly and Company. Sintilimab is a type of immunoglobulin G4 monoclonal antibody, which binds to PD-1 molecules on the surface of T-cells, blocks the PD-1 / PD-Ligand 1 (PD-L1) pathway, and reactivates T-cells to kill cancer cells.[iii]

In China, sintilimab has been approved and included in the updated NRDL for seven indications. The updated NRDL reimbursement scope for TYVYT (sintilimab injection) includes:

For the treatment of relapsed or refractory classic Hodgkin’s lymphoma after two lines or later of systemic chemotherapy;
For the first-line treatment of unresectable locally advanced or metastatic non-squamous non-small cell lung cancer lacking EGFR or ALK driver gene mutations;
For the treatment of patients with EGFR-mutated locally advanced or metastatic non-squamous non-small cell lung cancer who progressed after EGFR-TKI therapy;
For the first-line treatment of unresectable locally advanced or metastatic squamous non-small cell lung cancer;
For the first-line treatment of unresectable or metastatic hepatocellular carcinoma with no prior systematic treatment;
For the first-line treatment of unresectable locally advanced, recurrent or metastatic esophageal squamous cell carcinoma;
For the first-line treatment of unresectable locally advanced, recurrent or metastatic gastric or gastroesophageal junction adenocarcinoma.
Furthermore, sintilimab’s eighth indication, in combination with fruquintinib for the treatment of patients with advanced endometrial cancer with pMMR tumors that have failed prior systemic therapy and are not candidates for curative surgery or radiation, was conditional approved by the NMPA in December 2024. And the NDA for sintilimab in combination with ipilimumab as neoadjuvant treatment for resectable MSI-H/dMMR colon cancer is under the NMPA review and has been granted Priority Review designation.

In addition, three clinical studies of sintilimab have met their primary endpoints:

Phase 2 study of sintilimab monotherapy as second-line treatment of esophageal squamous cell carcinoma;
Phase 3 study of sintilimab monotherapy as second-line treatment for squamous non-small cell lung cancer with disease progression following platinum-based chemotherapy;
Phase 2/3 study of sintilimab in combination with fruquintinib versus axitinib or everolimus monotherapy for the second-line treatment of advanced RCC.
About Fruquintinib

Fruquintinib is a selective oral inhibitor of all three vascular endothelial growth factor (VEGF) receptors (VEGFR-1, -2 and -3). VEGFR inhibitors play a pivotal role in inhibiting tumor angiogenesis. Fruquintinib was designed to have enhanced selectivity that limits off-target kinase activity, allowing for drug exposure that achieves sustained target inhibition and flexibility for potential use as part of a combination therapy.[iv]

About Fruquintinib Approvals

Fruquintinib is co-developed and co-marketed in China by HUTCHMED and Eli Lilly and Company under the brand name ELUNATE. It is approved for the treatment of patients with metastatic colorectal cancer who have previously received fluoropyrimidine, oxaliplatin and irinotecan-based chemotherapy, and those who have previously received or are not suitable for receiving anti-VEGF therapy or anti-epidermal growth factor receptor (EGFR) therapy (RAS wild-type) in China. It was included in the China National Reimbursement Drug List (NRDL) in January 2020. Since its launch in China, over 100,000 patients with colorectal cancer have been treated with fruquintinib.

The combination of ELUNATE (fruquintinib) and TYVYT (sintilimab injection) has conditional approval in China for the treatment of patients with advanced endometrial cancer with Mismatch Repair proficient (pMMR) tumors that have failed prior systemic therapy and are not candidates for curative surgery or radiation.

Takeda holds the exclusive worldwide license to further develop, commercialize, and manufacture fruquintinib outside mainland China, Hong Kong and Macau, marketing it under the brand name FRUZAQLA. Fruquintinib received approval for the treatment of previously treated metastatic colorectal cancer in the US in November 2023, in the EU in June 2024, in Switzerland and Argentina in August 2024, in Canada, Japan and the United Kingdom in September 2024, in Australia and Singapore in October 2024 and in Israel and the United Arab Emirates in December 2024. Regulatory applications are progressing in many other jurisdictions.

The global regulatory submissions are based on data from two large, randomized, controlled Phase III trials in colorectal cancer, the global, multi-regional FRESCO-2 trial and the FRESCO trial conducted in China, showing consistent benefit among a total of 734 metastatic colorectal cancer patients treated with fruquintinib. Safety profiles were consistent across trials. Results from the FRESCO-2 trial were published in The Lancet in June 2023,[v] while results from the FRESCO trial were published in The Journal of the American Medical Association, JAMA.[vi]

The safety and efficacy of fruquintinib for the following investigational uses have not been established and there is no guarantee that it will receive health authority approval or become commercially available in any country for the uses being investigated:

About Fruquintinib for Second-line Treatment of RCC

The U.S. Food and Drug Administration (FDA) has approved five immune-oncology combination therapies for the first-line treatment of advanced RCC. However, only one immune-oncology combination therapy has been approved in China for advanced RCC patients classified as having intermediate or poor risk by the International mRCC Database Consortium (IMDC). Single-agent targeted therapy continues to be one of the primary choices for first-line treatment of advanced RCC in China. Notably, advanced RCC patients who have experienced failure with single-agent targeted therapy previously still indicate an unmet medical need.

Results from a proof-of-concept Phase Ib/II study of fruquintinib plus sintilimab were published in Targeted Oncology in January 2025. The combination demonstrated promising efficacy and a tolerable safety profile in this setting. At the data cutoff of October 9, 2024, all 20 enrolled previously treated patients were evaluable for efficacy, with a median follow-up duration of 45.7 months. The confirmed ORR was 60.0% and DCR was 85.0%. Median DoR was 13.9 months and median PFS was 15.9 months. Overall survival ("OS") was not reached, and the 36-month OS rate was 58.3%.