On August 20, 2025 Larkspur Biosciences, a company pioneering a new wave in cancer therapy that destroys tumors by targeting cancer cell fitness, reported the discovery of LRK-4189, a first-in-class degrader of the lipid kinase PIP4K2C for the treatment of microsatellite stable (MSS) colorectal cancer (CRC) and other solid tumors (Press release, Larkspur Biosciences, AUG 20, 2025, View Source [SID1234655402]). The announcement was made at a presentation Larkspur was invited to give at the prestigious MEDI First Time Disclosures: Breakthroughs on New Medicines session at ACS Fall 2025, a meeting of the American Chemical Society in Washington, DC.

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Cancer cells maintain their fitness by developing survival adaptations that foster escape from intrinsic and extrinsic mechanisms of cell death in conditions of stress. Phosphatidylinositol 5-phosphate 4-kinase, type II, gamma (PIP4K2C) is a lipid kinase associated with poor outcomes in a range of cancers including CRC and breast cancers. PIP4K2C is co-opted by cancer cells to increase their fitness by evading immune surveillance and adapting to stress.

"Genetic studies have long highlighted PIP4K2C as a key player in cancer stress adaptation, but its extremely low kinase activity made it resistant to conventional inhibition approaches," said Catherine Sabatos-Peyton, PhD, CEO of Larkspur Biosciences. "With our novel degrader, LRK-4189, we’ve finally unlocked this critical pathway. By reducing cancer cell fitness, triggering intrinsic apoptosis, and engaging the immune system to clear residual tumor cells, LRK-4189 has the potential to overcome the limitations of earlier therapies. We’re excited to advance this promising therapy to the clinic later this year."

According to the American Cancer Society, in the United States, approximately 150,000 cases of CRC are diagnosed annually, with MSS CRC accounting for about 85% of all CRC cases.

About LRK-4189

LRK-4189 is an orally bioavailable, selective degrader of PIP4K2C with subnanomolar potency in primary human cells.
LRK-4189-mediated degradation of PIP4K2C leads to intrinsic cancer cell death and activates interferon signaling, triggering multiple killing mechanisms in difficult-to-treat MSS CRC cells.
In vivo, LRK-4189 demonstrates dose dependent PKPD with single agent efficacy in multiple models of CRC and synergy with first-line standard of care chemotherapy.
In primary human CRC patient-derived spheroids, 50% of patient samples respond to LRK-4189 with a preferential response in MSS CRC, which compares favorably to benchmark cetuximab in the same platform (35%). Cetuximab may be either a first- or second-line treatment in people with RAS wild type CRC.
LRK-4189 has completed IND-enabling studies and expects to initiate a Phase 1 clinical trial in Q4 2025.

On August 20, 2025 I-Mab (NASDAQ: IMAB) (I-Mab or the Company), a U.S.-based, global biotech company, focused on the development of precision immuno-oncology agents for the treatment of cancer, reported financial results for the three and six months ended June 30, 2025, and highlighted recent pipeline progress and business updates (Press release, I-Mab Biopharma, AUG 20, 2025, View Source [SID1234655401]).

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"The first half of 2025 has been transformative for I-Mab," said Sean Fu, PhD, Chief Executive Officer of I-Mab. "Our presentation at ESMO (Free ESMO Whitepaper) GI showcased compelling Phase 1b combination data for givastomig, reinforcing our confidence in its potential to be a best-in-class Claudin 18.2-directed therapy for metastatic gastric cancers in the 1L setting. Thanks to strong study momentum and active investigator engagement, we completed enrollment of the planned Phase 1b dose expansion cohorts ahead of schedule and expect to report topline data in Q1 2026. We believe our strong cash position and unwavering focus on value creation, position I-Mab to deliver meaningful clinical data and improve the lives of patients."

Recent and Anticipated Upcoming Clinical Milestones

Givastomig (CLDN18.2 x 4-1BB bispecific):

Recent Developments:

•
Positive Phase 1b Dose Escalation Data in Combination with Immunochemotherapy Presented at ESMO (Free ESMO Whitepaper) GI 2025 – Data from the dose escalation cohorts of the study were presented on July 2, 2025 in a Mini Oral presentation at the European Society for Medical Oncology Gastrointestinal Cancers Congress (ESMO GI) 2025 in Barcelona, Spain, accessible here. The data showed that givastomig in combination with immunochemotherapy demonstrated an 83% (10/12) objective response rate (ORR) at the doses (8 mg/kg and 12 mg/kg) selected for dose expansion. The responses were rapid, durable and deepened over time, with a favorable overall safety profile.
I-Mab hosted a virtual investor event on July 8, 2025 reviewing the Phase 1b dose escalation data (accessible for viewing here).

•
Givastomig Monotherapy Data Published in Clinical Cancer Research – First-in-human monotherapy data for givastomig were published in Clinical Cancer Research, a journal of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) (CCR), and a highly-ranked clinical oncology publication. The CCR paper details promising clinical data showing that givastomig monotherapy achieved an ORR of 16% in heavily pretreated Claudin 18.2-positive gastric cancer patients without encountering a dose limiting toxicity or maximum tolerated dose. The publication can be accessed here. The study provided the foundation for the ongoing Phase 1b combination study.
Upcoming Potential Clinical Milestones: I-Mab completed enrollment in the planned Phase 1b dose expansion study evaluating givastomig in combination with nivolumab and mFOLFOX6 for first line (1L) metastatic gastric cancers. The Company expects to present topline data in Q1 2026.

Other Programs: I-Mab anticipates updates in 2026 for ragistomig (PD-L1 x 4-1BB bispecific) and uliledlimab (monoclonal antibody targeting CD73), which are currently under development by ABL Bio and TJ Biopharma, respectively.

Corporate Developments

•
I-Mab Announces Pricing of $65 Million Underwritten Offering – I-Mab completed an underwritten offering of American Depositary Shares (ADSs) representing ordinary shares that raised total net proceeds of approximately $61.2 million. The offering included participation from new and existing investors including Everest Medicines, Janus Henderson Investors, Adage Capital Partners LP and Exome Asset Management.

•
Givastomig Intellectual Property Portfolio Strengthened with Acquisition of Bridge Health – The acquisition provides I-Mab with upstream rights to the Claudin 18.2 parental antibody for use in bispecific and multi-specific applications, eliminates all royalty obligations and reduces future milestones for givastomig due to Bridge Health Biotech Co., Ltd. (Bridge Health) by I-Mab. The transaction is expected to close in Q3 2025.
Cash Position

As of June 30, 2025, the Company had cash and cash equivalents, and short-term investments of $165.6 million. The Company expects that its existing cash and cash equivalents, and short-term investments, together with the net proceeds from the August 2025 underwritten offering, will be sufficient to fund its operating expenses and capital expenditure requirements through the fourth quarter of 2028, including through a randomized Phase 2 trial of givastomig.

Shares Outstanding

As of June 30, 2025, the Company had 188,108,178 ordinary shares issued and outstanding, representing the equivalent of 81,786,164 ADSs, assuming the conversion of all ordinary shares into ADSs. In August 2025, the Company announced an underwritten offering of 76,666,659 ordinary shares, representing the equivalent of 33,333,330 ADSs.

Pro-forma for the underwritten offering, the Company had 264,774,837 ordinary shares issued and outstanding, representing the equivalent of 115,119,494 ADSs, assuming the conversion of all ordinary shares into ADSs.

Research and Development Expenses

Research and development (R&D) expenses were $3.3 million and $4.1 million for the three and six months ended June 30, 2025, respectively, compared to $5.2 million and $11.3 million for the three and six months ended June 30, 2024, respectively. R&D expenses for the three months ended June 30, 2025 were $1.9 million lower than the comparable period in 2024, primarily due to lower contract research organization costs driven by streamlined clinical pipeline activities and a decrease in employee-related expenses resulting from a lower headcount. R&D expenses for the six months ended June 30, 2025 were $7.2 million lower than the comparable period in 2024, primarily due to reimbursements recognized under an existing collaboration agreement and lower contract research organization costs due to streamlined clinical pipeline activities.

Administrative Expenses

Administrative expenses were $3.8 million and $8.3 million for the three and six months ended June 30, 2025, respectively, compared to $11.9 million and $14.4 million for the three and six months ended June 30, 2024, respectively. Administrative expenses for the three months ended June 30, 2025 were $8.1 million lower than the comparable period in 2024, primarily due to lower legal expenses and a decrease in employee-related expenses resulting from a lower headcount. Administrative expenses for the six months ended June 30, 2025 were $6.1 million lower than the comparable period in 2024, primarily due to a decrease in legal expenses and lower employee benefit and compensation expenses resulting from a lower headcount. This decrease was partially offset by a higher employee share-based compensation expense in the current period. The employee share-based compensation expense during the six months ended June 30, 2024 included forfeitures in connection with the divestiture of our Chinese assets and related operations (the Greater China assets and business operations).

Interest Income

Interest income was $1.8 million and $3.7 million for the three and six months ended June 30, 2025, respectively, compared to $2.1 million and $2.8 million for the three and six months ended June 30, 2024, respectively. Interest income for the three months ended June 30, 2025 was $0.3 million lower than the comparable period in 2024 due to lower average cash balances and lower market interest rates. Interest income for the six months ended June 30, 2025 was $0.8 million higher than the comparable period in 2024, primarily due to greater interest earned on cash balances as a result of cash management strategies.

Other Income (Expenses), Net

Other income (expenses), net were $(0.2) million and $0.1 million for the three and six months ended June 30, 2025, respectively, compared to $6.1 million and $5.5 million for the three and six months ended June 30, 2024, respectively. The $6.3 million and $5.4 million decreases in other income (expense), net for the three and six months ended June 30, 2025, respectively, were primarily attributable to the changes in fair value and extinguishment of certain put right liabilities. The decrease was partially offset by smaller impacts from foreign exchange losses recognized during the current period.

Equity in Loss of Affiliates

Equity in loss of affiliates was $(1.0) million for the six months ended June 30, 2024 due to recognition of the employee stock ownership plan expenses from the Company’s unconsolidated investee as a result of the divestiture of the Greater China assets and business operations. There was no equity in loss of affiliates for the three months ended June 30, 2024 or the three and six months ended June 30, 2025.

Net Loss from Continuing Operations

Net loss from continuing operations were ($5.5) million and $(8.7) million for the three and six months ended June 30, 2025, respectively, compared to $(8.9) million and $(18.4) million for the three and six months ended June 30, 2024, respectively. Net loss from continuing operations per share attributable to ordinary shareholders were $(0.03) and $(0.05) for the three and six months ended June 30, 2025, respectively, compared to $(0.05) and $(0.10) for the three and six months ended June 30, 2024, respectively.

Net Gain from Discontinued Operations

On April 2, 2024, the Company closed the divestiture of the Greater China assets and business operations announced on February 7, 2024 (the Transaction). In accordance with ASC 205-20, the Company determined that the Transaction represented a strategic shift that had a major effect on the business and therefore, met the criteria for classification as discontinued operations. As a result, the Company recognized a loss from discontinued operations of $6.9 million for the six months ended June 30, 2024 and a gain from sale of discontinued operations of $34.4 million for the three and six months ended June 30, 2024.

Net Income (Loss)

Net income (loss) was $(5.5) million and $(8.7) million for the three and six months ended June 30, 2025, respectively, compared to $25.4 million and $9.1 million for the three and six months ended June 30, 2024, respectively. Net income (loss) per share attributable to ordinary shareholders was $(0.03) and $(0.05) for the three and six months ended June 30, 2025, respectively compared to $0.13 and $0.05 for the three and six months ended June 30, 2024, respectively.

About Givastomig

Givastomig (TJ033721 / ABL111) is a bispecific antibody targeting Claudin 18.2 (CLDN18.2)-positive tumor cells. It conditionally activates T cells through the 4-1BB signaling pathway in the tumor microenvironment where CLDN18.2 is expressed. Givastomig is being developed for first line (1L) metastatic gastric cancers, with further potential in other solid tumors. In Phase 1 trials, givastomig has shown promising anti-tumor activity attributable to a potential synergistic effect of proximal interaction between CLDN18.2 on tumor cells and 4-1BB on T cells in the tumor microenvironment, while minimizing toxicities commonly seen with other 4-1BB agents.

An ongoing Phase 1b study is evaluating givastomig for the treatment of gastric cancer in the 1L setting in combination with standard of care, nivolumab (an anti-PD-1 checkpoint inhibitor) plus chemotherapy, in dose escalation (n=17) and dose expansion (n=40) cohorts. The study builds on positive Phase 1 monotherapy data.

Givastomig is being jointly developed through a global partnership with ABL Bio, in which I-Mab is the lead party and shares worldwide rights, excluding Greater China and South Korea, equally with ABL Bio.

On August 20, 2025 Circle Pharma, Inc., a clinical-stage biopharmaceutical company pioneering next-generation targeted macrocycle therapeutics for difficult-to-treat cancers, reported a Nature publication describing robust pre-clinical tumor suppression and novel mechanistic insights from inhibiting the binding of certain protein substrates (that bind via RxL motifs) to cyclins A and B in E2F-high tumor cells (Press release, Circle Pharma, AUG 20, 2025, View Source [SID1234655399]). Circle Pharma’s oral cyclin A/B RxL inhibitor, CID-078, is a first-in-class, orally bioavailable macrocycle with dual cyclin A and B RxL inhibitory activity that is being evaluated in a Phase 1 clinical trial for patients with advanced solid tumors.

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Cyclins (including cyclins A and B) are a family of proteins that function as master regulators of the cell cycle by binding to and activating their catalytic partners, the cyclin-dependent kinases (CDKs). Cancers driven by high E2F activity, such as small cell lung cancer (SCLC) and other tumors with RB1 alterations, have an overactive cell cycle that leads to uncontrolled tumor cell proliferation. In preclinical models, cyclin A/B RxL inhibitors:

Blocked the cyclin A-E2F interaction, triggering aberrant sustained E2F activity, DNA damage, and replication stress.
Subsequently disrupted the cyclin B-Myt1 interaction, removing a critical safety brake and forcing damaged tumor cells through division, causing tumor cell death.
Produced robust anti-tumor activity, including in chemotherapy-resistant SCLC patient-derived xenograft models.
The publication, which was co-authored by scientists from Circle Pharma and the Dana-Farber Cancer Institute, Harvard Medical School, the University of Texas Southwestern Medical Center, and the University of Oxford, can be accessed here (doi: 10.1038/s41586-025-09433-w).

"We are excited to have the novel biology and compelling anti-cancer effects of the cyclin A/B RxL inhibitors developed at Circle recognized within the broader scientific community through this publication in Nature," said David J. Earp, J.D., Ph.D., president and chief executive officer of Circle Pharma. "This work underscores the capabilities of our MXMO platform to generate oral, cell-permeable macrocycle therapies, such as CID-078, including for historically undruggable targets such as cyclins. With our first-in-human Phase 1 study of CID-078 well underway, we are eager to see the innovative research outlined in this publication translate into new, high-impact therapeutic options for people living with cancer."

"These findings build upon previous work and reveal additional gain-of-function mechanisms through which cyclin A/B RxL inhibition triggers apoptosis in cancer cells, further supporting this approach for E2F-driven cancers, such as cancers with RB1 alterations, which includes nearly all SCLCs, up to half of triple-negative breast cancers, and subsets of other solid tumors," said Matthew G. Oser, M.D., Ph.D., senior author of the publication and associate professor of medicine at Dana-Farber Cancer Institute and Harvard Medical School. "Circle Pharma’s cell-permeable, oral macrocycles are designed to overcome the limitations of other therapeutic modalities and are ideally positioned to access cyclins and other historically undruggable targets, offering exciting potential for patients with cancer."

About CID-078, Circle Pharma’s Oral Cyclin A/B RxL Inhibitor Program

CID-078 is an orally bioavailable macrocycle with dual activity blocking protein-protein interactions between both cyclins A and B and key substrates that bind to them via conserved RxL motifs. CID-078 selectively targets tumor cells with oncogenic alterations that cause cell cycle dysregulation, including alterations in the tumor suppressor RB1. In pre-clinical studies, Circle Pharma’s cyclin A/B RxL inhibitors have been shown to potently and selectively disrupt the protein-to-protein interaction between cyclins A and B and their key substrates and modulators, including E2F (a substrate of cyclin A) and MYT1 (a modulator of cyclin B). Preclinical studies have demonstrated the ability of these cyclin A/B RxL inhibitors to cause single-agent tumor regressions in multiple in vivo models. A multi-center Phase 1 clinical trial (NCT06577987) is currently enrolling patients with advanced solid tumors harboring RB1 alterations.

On August 20, 2025 Anixa Biosciences, Inc. ("Anixa" or the "Company") (NASDAQ: ANIX), a biotechnology company focused on the treatment and prevention of cancer, reported that the Chinese National Intellectual Property Administration (CNIPA) has issued a Notice of Allowance for a new patent related to its breast cancer vaccine technology (Press release, Anixa Biosciences, AUG 20, 2025, https://ir.anixa.com/news/detail/1094/anixa-biosciences-receives-notice-of-allowance-from-chinese-national-intellectual-property-administration-for-patent-covering-breast-cancer-vaccine-technology [SID1234655398]). This patent, exclusively licensed from Cleveland Clinic, will provide composition of matter protection for the Company’s novel approach to breast cancer treatment and prevention in China.

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With this allowance, Anixa continues to expand the international scope of its intellectual property portfolio, reinforcing its leadership in the field of cancer immunotherapy. The Chinese patent complements patents issued in the United States and other key global jurisdictions, and represents an important step toward future regulatory and commercial efforts outside the U.S.

"This newly allowed patent further illustrates the continued recognition of the novelty and potential of our breast cancer vaccine," stated Dr. Amit Kumar, Chairman and CEO of Anixa Biosciences. "As we continue advancing clinical development in the U.S., this allowance further strengthens our ability to pursue strategic global opportunities in regions with a high burden of breast cancer."

Breast cancer has become the most commonly diagnosed cancer among women in China, with incidence rising steadily over the past two decades and hundreds of thousands of new cases each year. As one of the world’s largest and fastest-growing patient populations, addressing this challenge is a critical public health priority, requiring innovative preventative solutions such as Anixa’s vaccine.

Anixa’s vaccine is based on immunizing against human α-lactalbumin, a protein associated with lactation that is aberrantly expressed in certain types of breast cancer. This "retired" protein strategy, developed at Cleveland Clinic and licensed exclusively to Anixa, aims to selectively prime the immune system to prevent tumor formation while avoiding harm to normal tissue.

By reinforcing its global patent estate, Anixa is laying the groundwork for future international development and commercialization strategies. The Company’s broader vaccine platform also targets other high-incidence cancers and is designed to transform how the medical community approaches cancer prevention.

On August 20, 2025 Alligator Bioscience (Nasdaq Stockholm: ATORX), a clinical-stage biotechnology company developing tumor-directed immuno-oncology antibody drugs, reported key highlights from its R&D event held on 19 August 2025 (Press release, Alligator Bioscience, AUG 20, 2025, View Source [SID1234655397]). The event featured presentations from Alligator’s management and scientific leadership, outlining Alligator’s clinical progress, upcoming milestones, and strategic outlook.

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Key takeaways from the event include:

Mitazalimab – Phase 3 readiness: Long-term follow-up data continue to demonstrate encouraging overall survival in metastatic pancreatic cancer, supporting the confirmed regulatory path and planned initiation of a Phase 3 trial.
Scientific insights: New translational biomarker data further expand and strengthen the rationale for mitazalimab in pancreatic cancer and other solid tumors, underscored by myeloid and T-cell activation and their correlation with improved clinical outcomes.
Trial completion and CMC status: The final, 30-month, data read-out from OPTIMIZE-1 is expected during Q3 2025. The trial will thereafter be finalized, with mitazalimab being provided to patients still on treatment, and sites with ongoing patients remain open under limited, risk-based monitoring; manufacturing of Phase 3 material has been successfully completed.
Investigator-initiated trials (IITs): Based on the significant investigator interest Alligator is engaged in a number of externally funded exploratory and Phase 2 clinical trials with mitazalimab across pancreatic, gastrointestinal and other solid tumors to expand mitazalimab’s future clinical use. Individual trials are expected to start during H2 2025 and the first half of 2026.
Pipeline updates: The HER2 antibody HLX22 (developed by Chinese Henlius) has entered a global Phase 3 trial in gastric cancers. Alligator expects to receive the next development milestone within 6–12 months, and estimates that its share of the future royalties will amount to SEK 150–400 million annually.
Strategic outlook: With a reduced burn-rate, Alligator is well positioned to advance mitazalimab into registrational trials together with a partner, and in parallel explore additional development options for the asset. Together mitazalimab and HLX22 represent a significant financial upside for Alligator. Other pipeline assets and technologies represent additional future development and income opportunities.