On March 3, 2025 Adicet Bio, Inc. (Nasdaq: ACET), a clinical stage biotechnology company discovering and developing allogeneic gamma delta T cell therapies for autoimmune diseases and cancer, reported the acceptance of two abstracts for poster presentations at the upcoming Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 2025 Spring Scientific Meeting taking place March 12-14, 2025, in San Diego, C.A (Press release, Adicet Bio, MAR 3, 2025, View Source [SID1234650863]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Details of the poster presentation are as follows:

Abstract Title: ADI-270, an Armored Allogeneic Anti-CD70 γδ CAR T Cell Therapy, Demonstrates Improved Efficacy and Safety in Preclinical Models Compared to Conventional αβ CAR Benchmarks
Poster/Abstract Number: 39
Presenting Author: Shon Green, Ph.D.
Date/Time: Wednesday, March 12, 2025, from 5:10 p.m. – 6:45 p.m. PT

Abstract Title: A Phase 1/2 First in Human Study of ADI-270, an Armored Allogeneic Anti-CD70 Chimeric Antigen Receptor γδ T Cell Therapy, in Relapsed or Refractory (R/R) Clear Cell Renal Cell Carcinoma (ccRCC)
Poster/Abstract Number: 136
Presenting Author: Gregory Vosganian, M.D.
Date/Time: Thursday, March 13, 2025, from 5:00 p.m. – 6:30 p.m. PT

On March 3, 2025 SOTIO Biotech, a clinical-stage biopharmaceutical company owned by PPF Group, reported the first preclinical data on SOT109, a novel antibody-drug conjugate (ADC) targeting cadherin-17 (CDH17) (Press release, SOTIO, MAR 3, 2025, View Source [SID1234650862]). The data highlight SOT109’s promising activity and tolerability profile across multiple disease models, reinforcing its potential to become a best-in-class therapeutic for the treatment of colorectal cancer and other gastrointestinal (GI) cancers. The findings were presented at the 15th World ADC London 2025, taking place from March 3 to 6 at Novotel London West, London, UK.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We are excited to share groundbreaking data on SOT109, an innovative ADC designed to treat colorectal cancer and other GI malignancies," said Martin Steegmaier, Ph.D., chief scientific officer of SOTIO. "CDH17 has long been recognized as a highly compelling therapeutic target, yet previous non-ADC and ADC approaches have faced significant obstacles. Our cutting-edge design overcomes these challenges, utilizing state-of-the-art linker-payload technology and an optimized antibody backbone to enhance efficacy and tumor selectivity. Preclinical data indicate that our candidate not only delivers potent tumor cell killing but does so with an excellent safety profile and high therapeutic index. We believe this represents a major advancement in ADC development for GI cancers, and we look forward to filing an Investigational New Drug (IND) application for this program in Q2 2026."

CDH17 is a highly promising target homogenously overexpressed in more than 90% of colorectal cancers (CRC) and abundantly expressed in other GI cancers, including gastric, pancreatic, and esophageal cancers. In contrast, its expression in normal adult tissues is largely restricted to the GI tract, reducing the risk of off-target toxicity.

As CDH17 is an abundantly expressed and rapidly internalizing transmembrane protein on GI cancer cells, CDH17 is ideally suited for an ADC-mediated drug delivery approach. SOT109 is a fully human and highly specific ADC with exceptional binding and internalization properties against CDH17. SOT109 utilizes Synaffix’s clinically validated ADC platform, incorporating the SYNtecan E proprietary linker-payload system that contains an exatecan payload (DAR=4). For the treatment of CRC, SOT109’s exatecan payload is expected to demonstrate superior activity, reduced susceptibility to resistance, and an enhanced bystander effect due to its high cell permeability, setting it apart from other ADC payloads utilized to date.

In preclinical studies presented at World ADC London, SOT109 exhibited strong anti-tumor activity across multiple mouse xenograft models, including complete responses. It demonstrated favorable tolerability in an exploratory mouse study at doses up to 150 mg/kg. Furthermore, data from a subsequent toxicity study in non-human primates (NHPs) revealed that SOT109 displays a favorable therapeutic index underscoring its potential as a transformative therapy for GI cancers.

On March 3, 2025 Laekna (2105.HK) reported that the U.S. Food and Drug Administration (FDA) has approved the IND for LAE120, an internally discovered USP1 inhibitor, for the treatment of advanced solid tumors (Press release, Laekna Therapeutics, MAR 3, 2025, View Source [SID1234650861]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

LAE120 is a novel, allosteric and highly potent USP1 inhibitor, displaying monotherapy potency and combination activity with PARP inhibitor in HRD (homologous recombination deficiency) cancers. It has a unique chemical structure differentiated from all the other disclosed USP1 inhibitors and is expected to induce a different conformational change in USP1. LAE120 shows robust tumor inhibitory activity across various xenograft models such as MDA-MB-436 and K562 as a single agent and exhibits synergistic effect in combination with PARP inhibitors. It also demonstrates good therapeutic windows in GLP long-term toxicology study. Laekna is actively exploring partnerships to accelerate the clinical development of LAE120.

"Leveraging our deep know-how and extensive expertise in drug discovery, Laekna has developed a distinctive portfolio of innovative drug candidates through the close collaboration of our Med Chem, Biology and AIDD (AI-driven Drug Discovery) teams, continuously advancing preclinical drug candidates into clinical stage. Laekna has also significantly accelerated the progress of drug discovery by utilizing cutting-edge artificial intelligence tools," said Dr. Justin Gu, Chief Scientific Officer of Laekna. "We look forward to bringing novel drugs to patients as swiftly as possible," he added.

Advancing Diversified Pipelines

Laekna is actively advancing preclinical drug candidates. In the fourth quarter of 2024, another internally discovered anti-tumor drug candidate, LAE118, a potentially best-in-class, mutant-selective PI3Kαinhibitor, has advanced to IND-enabling study. PI3Kα mutations are prevalent in patients with breast, colorectal, lung, endometrial, and numerous other cancers. However, the first-generation drugs targeting PI3Kα inhibit the wild-type and mutant PI3Kα with equal potency, which raises concerns of tolerability and therapeutic efficacy.

As a novel allosteric inhibitor, LAE118 demonstrates excellent potency and selectivity towards various PI3Kα mutants. With superior anti-cancer efficacy and tolerability than other current PI3Kα inhibitors, LAE118 is potentially the best-in-class pan-mutant-selective PI3Kα inhibitor. Laekna has presented the preclinical characterization of LAE118 at the San Antonio Breast Cancer Symposium (SABCS) in December 2024. LAE118 is in IND-enabling studies and IND is expected to be filed in the fourth quarter of 2025.

Strategic Partnerships to Accelerate Globalization

"We will continue to advance and expand our product portfolio in the therapeutic areas where we have accumulated tremendous experience and extensive know-how," said Dr. Chris Lu, Chief Executive Officer of Laekna. "In November 2024, the Group has entered into a clinical collaboration agreement with Lilly (NYSE:LLY) to support and accelerate global clinical development of LAE102 for the treatment of obesity. We plan to pursue strategic partnerships with global leading pharmaceutical companies to accelerate clinical development and commercialization of our drug candidate assets. We keep advancing and expanding our pipeline and are committed to bringing life-changing medicines to more people around the world," he added.

On March 3, 2025 Nuvation Bio Inc. (NYSE: NUVB), a global biopharmaceutical company tackling some of the greatest unmet needs in oncology, reported non-dilutive financings of up to $250 million with Sagard Healthcare Partners (Sagard) (Press release, Nuvation Bio, MAR 3, 2025, View Source [SID1234650860]). The transaction comprises a royalty interest financing of $150 million and a senior term loan of up to $100 million. These financings strengthen Nuvation Bio’s balance sheet to fully fund commercialization of taletrectinib in the U.S., if approved, and development of the Company’s current clinical-stage pipeline. The transaction also provides Nuvation Bio with a path to potential profitability without the need to raise additional capital.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"This transaction is a significant milestone for Nuvation Bio as we prepare to bring taletrectinib to the U.S. market, subject to FDA approval, in mid-2025," said David Hung, M.D., Founder, President, and Chief Executive Officer of Nuvation Bio. "With these financings, we are well positioned to launch taletrectinib and drive continued development of our clinical-stage pipeline—all without the need for additional fundraising. This also improves our flexibility to pursue strategic opportunities to deploy our capital. We are thrilled to have support from Sagard and appreciate their shared confidence in taletrectinib and Nuvation Bio as we continue toward our goal of improving outcomes for patients with cancer."

Subject to the approval of taletrectinib by the U.S. Food and Drug Administration (FDA) on or prior to September 30, 2025, Sagard will provide Nuvation Bio with an upfront cash payment of $150 million. In return, Sagard will receive tiered royalties on U.S. net sales of taletrectinib, including 5.5% of annual U.S. net sales up to $600 million and 3.0% of annual U.S. net sales between $600 million and $1 billion. Nuvation Bio will retain all annual U.S. net sales above $1 billion. Payments to Sagard will cease upon the earliest occurrence of total royalties reaching 1.6 times its investment by June 30, 2031, 1.75 times its investment by June 30, 2034, or 2.0 times its investment thereafter.

"We are excited to partner with Nuvation Bio, an organization with deep oncology expertise and a commitment to delivering transformative therapies," said Raja Manchanda, Partner at Sagard Healthcare Partners. "We believe taletrectinib has the potential to redefine the treatment landscape for patients with ROS1-positive non-small cell lung cancer, and we are pleased to provide a structured financing that supports both potential near-term commercialization and long-term growth."

In addition to the royalty financing, Sagard has committed to a 5-year, senior secured term loan of up to $100 million, with $50 million to be funded upon U.S. FDA approval of taletrectinib on or prior to September 30, 2025. The second tranche of $50 million is available at Nuvation Bio’s option until June 30, 2026, as long as Nuvation Bio has achieved first U.S. commercial sale of taletrectinib. The term loan will bear interest at SOFR + 6.00%, subject to a 4.00% SOFR floor. There are no scheduled amortization payments associated with the term loan, with all outstanding principal due at maturity.

TD Cowen served as financial advisor and Cooley LLP served as legal advisor to Nuvation Bio. Sidley Austin LLP served as legal advisors to Sagard.

On March 3, 2025 Silexion reported the completion of its initial study evaluating SIL-204 in orthotopic pancreatic cancer models, a critical milestone that could continue to position its next-generation RNAi therapy at the forefront of KRAS-driven cancer treatment (Press release, Silexion Therapeutics, MAR 3, 2025, View Source [SID1234650859]). With data analysis now underway and initial results expected in the coming weeks, according to the company’s latest announcement, anticipation seems high for what could be a pivotal breakthrough, if indeed the data is positive.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

A Potential Step Toward Transforming Pancreatic Cancer Treatment

Silexion’s latest study could mark an important advancement in validating systemic administration of SIL-204. The study specifically assessed the therapy’s ability to reduce primary tumor growth and inhibit metastatic spread in clinically relevant orthotopic pancreatic cancer models—providing a more accurate representation of human disease progression than traditional subcutaneous xenograft models.

Silexion’s work with SIL-204 has already demonstrated compelling preclinical efficacy, including a 50% reduction in tumor growth and complete necrosis in half of treated tumors in previous systemic administration studies. Moreover, SIL-204 has shown sustained therapeutic levels for over 56 days from a single dose—an unprecedented achievement in RNAi-based therapies for KRAS-driven cancers.

Why This Matters: A Potential First for Metastatic Pancreatic Cancer

KRAS-driven cancers remain among the most aggressive and difficult-to-treat malignancies, particularly in pancreatic cancer, where over 90% of tumors harbor KRAS mutations. While other companies have attempted to target KRAS with small molecule inhibitors, Silexion’s RNAi-based approach aims to silence multiple key KRAS mutations, including G12D, G12V, G12R, Q61H, and G13D—offering a broader and potentially more effective therapeutic strategy.

The ability to target both primary and metastatic pancreatic cancer via systemic administration would represent a major breakthrough, as Silexion has not previously demonstrated this effect in metastatic models. If the orthotopic model results show significant impact on metastases, this could mark a critical validation step, potentially differentiating SIL-204 from existing KRAS-targeting approaches and opening the door to expanded clinical applications.

The industry seems to be closely watching Silexion’s progress in light of the recent wave of multi-billion-dollar acquisitions in precision oncology. With major players like Pfizer acquiring Seagen for $43 billion and AbbVie purchasing Immunogen for $10.1 billion, the demand for novel cancer therapies seems to have increased in recent years. According to news reports, Maxim Group recently reaffirmed its strong buy rating on SLXN with a $9 price target, citing the company’s strong clinical trajectory and the ongoing validation of its RNAi platform.

Upcoming Data Readout: A Potential Critical Catalyst

Silexion’s announcement that initial results from the orthotopic model study will be released in March 2025 has sparked significant interest. If the data is positive, it could provide further confirmation of SIL-204’s ability to target both primary and metastatic pancreatic cancer, marking the first time the company demonstrates systemic efficacy against metastatic disease.

If the upcoming results align with previous systemic administration findings and show significant impact on metastases, SIL-204 could emerge as a leading next-generation RNAi therapy for KRAS-driven cancers—potentially, in the future, reshaping the treatment paradigm for one of the deadliest malignancies.

Silexion Therapeutics has continued to execute on its strategy, pushing the boundaries of RNAi therapeutics for one of the most aggressive cancers. With data from the orthotopic pancreatic cancer study expected in March, many will likely be watching closely. If the upcoming results are positive and demonstrate impact on metastases, they could serve as a major catalyst for the company, potentially redefining its role in the precision oncology landscape.

Given the strong track record of preclinical success, increasing interest, and a competitive landscape ripe for M&A activity, Silexion Therapeutics is undoubtedly a company to watch in 2025.