On May 8, 2025 Marengo Therapeutics, Inc., a clinical-stage biotechnology company pioneering novel approaches to precision T cell activation, reported that the first patient has been dosed in its STARt-002 clinical trial. The Phase 1b/2 study evaluates the safety and efficacy of Marengo’s lead clinical T cell agonist in combination with Trodelvy (sacituzumab govitecan-hziy), Gilead’s approved TROP2-directed antibody-drug conjugate (ADC), in patients with metastatic breast cancer (mBC) (Press release, Marengo Therapeutics, MAY 8, 2025, View Source [SID1234652784]).

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"The growing body of evidence supporting combinations of ADCs and immunotherapies is encouraging, including the recent success of the ASCENT-04 trial combining sacituzumab govitecan with pembrolizumab in metastatic TNBC," said Steven Isakoff, M.D., Ph.D., Medical Oncologist and Director of Breast Cancer Clinical Research at Massachusetts General Hospital. "Invikafusp alfa is a novel bi-specific immunotherapy designed as a dual T cell agonist, and the recent AACR (Free AACR Whitepaper) presentation highlighting its single-agent activity in PD-1 resistant tumors is particularly compelling. Coupled with preclinical evidence of efficacy in breast cancer models, this combination with an ADC offers a promising and innovative approach to expanding immunotherapy options for patients with both HR+/HER2- and triple-negative breast cancers."

STARt-002 (NCT06827613) is a Phase 1b/2 trial, beginning with a run-in phase to determine the optimal tolerated combined dose of the two agents, followed by dose expansion in two patient cohorts: metastatic triple-negative breast cancer (mTNBC) and hormone receptor-positive, HER2-negative (HR+/HER2−) metastatic breast cancer.

The study is currently enrolling patients at three leading North American cancer centers: Massachusetts General Hospital, Sarah Cannon Research Institute, and Princess Margaret Cancer Centre, with additional sites expected to join soon.

"As presented in recent SITC (Free SITC Whitepaper), EMSO IO and AACR (Free AACR Whitepaper) meetings, invikafusp clearly demonstrates promising monotherapy activity in PD-1 resistant tumors including MSS CRC and PD-1 negative NSCLC," said Kevin Chin, M.D., Chief Medical Officer of Marengo Therapeutics. "These data reinforce our belief that invikafusp could serve as a best-in-class immunotherapy backbone for multiple tumor types, particularly when paired with ADCs in immunologically cold tumors such as breast cancer. We are honored to partner with world-class clinical investigators to explore this promising combination for patients with high unmet needs."

On May 8, 2025 BioDlink, a leading global CDMO, reported that it congratulates its partner Junshi Biosciences (HKEX-1877; SSE-688180), on receiving Investigational New Drug (IND) approval from the National Medical Products Administration (NMPA) of China to initiate clinical trials for the JS212 injection — Junshi Biosciences’ first bispecific antibody-drug conjugate (ADC) (Press release, Shanghai Junshi Bioscience, MAY 8, 2025, View Source [SID1234652783]).

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JS212 represents a new class of bispecific ADCs that combine the humanized epidermal growth factor receptor and human epidermal growth factor receptor 3 bispecific antibody-drug conjugate to target both EGFR and HER3 — two proteins highly expressed in a variety of tumor cells, such as lung cancer, breast cancer, and head and neck cancer. As a bispecific ADC, JS212 has a key advantage over traditional ADCs that only target one protein: it can attack tumors via either EGFR or HER3, potentially increasing its effectiveness against a wider range of cancers and helping to overcome drug resistance.

Dr. Jun Liu, CEO and Executive Director of BioDlink, stated: "As a leader in ADC technology, BioDlink remains committed to technology innovation and one-stop solution platform for complex biologics. Our collaboration with Junshi Biosciences is built on mutual trust and deep experience in ADC research, development and manufacturing. The IND approval of JS212 — a technically demanding bispecific ADC —­ highlights our strong capabilities and strategic value we bring to partners pursuing next-generation biologics. We’re honored to support the advancement of this important program."

Dr. Jing Tong, Deputy Director of Junshi Biosciences’ Innovation Research Institute, shared: "We are very pleased with the ongoing and highly productive partnership with BioDlink. Their exceptional expertise and proven capabilities in ADC development and manufacturing have played a pivotal role in advancing JS212 to this important milestone. Throughout the collaboration, BioDlink has consistently demonstrated technical excellence, operational efficiency, and a deep understanding of complex bispecific ADCs. This approval marks a key collaboration milestone, and we look forward to deepening our cooperation as we work toward bringing innovative therapies to patients in the future."

BioDlink is committed to becoming a trusted CDMO biologics partner. The company operates a large-scale commercial biologics production site that meets international GMP standards and includes multiple integrated production lines for antibodies and ADCs.

With a comprehensive ADC platform supported by key R&D technologies, BioDlink enables efficient, centralized production of antibody intermediates, drug substances, and finished products. This setup accelerates timelines and reduces tech transfer costs. At the same time, BioDlink’s quality system is built according to international standards and has passed GMP audits in multiple countries, which can empower global customers.

On May 8, 2025 iOnctura, a clinical-stage biopharmaceutical company combating neglected and hard-to-treat cancers, reported it has dosed the first patient in the randomized Phase I/II study investigating lead asset roginolisib in combination with dostarlimab with or without docetaxel, in patients with advanced non-small cell lung cancer (NSCLC) (Press release, iOnctura, MAY 8, 2025, View Source [SID1234652782]).

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NSCLC is the most common type of lung cancer. Lung cancer is the leading cause of cancer death globally, accounting for approximately 1 in 5 of all cancer deaths[1].

Anti-programmed death-ligand 1 (PD-L1) or anti-programmed cell death protein 1 (PD1) immunotherapy is a standard therapy for NSCLC patients with no actionable mutations in the first or second lines of therapy, with or without chemotherapy. However, treatment is often of limited duration as the cancer cells develop resistance to the treatment. Rebalancing the immune system via PI3Kδ inhibition is thought to re-invigorate anti-tumour immune cells and thus is a promising mechanism to overcome resistance to current immunotherapies[2].

Michele Maio, MD, PhD, Professor of Medical Oncology at the University of Siena and Director of the Center for Immuno-Oncology at the University Hospital of Siena (Italy), Primary Coordinating Investigator of the Phase I/II study said: ‘There is a significant lack of treatment options for NSCLC patients who have progressed on immunotherapy and chemotherapy. We will be investigating whether the combination of roginolisib with dostarlimab and +/- chemotherapy can be given safely and may provide a novel treatment option in patients who no longer respond to their current treatment.’

Emerging clinical and translational biomarker data supports the hypothesis that combining roginolisib with an anti-PD-L1/PD1 agent, with or without docetaxel, may prevent or reverse drug resistance in NSCLC and may show synergistic anti-tumor immune activity without significant addition of toxicity. Firstly, the combination of anti-PD1 and roginolisib had an anti-tumor effect in vitro[3]. Secondly, ex vivo evaluation of NSCLC samples from patients responding and failing to immunotherapy showed that roginolisib rebalanced the composition of immune cells by inhibiting regulatory T-cells and enhancing CD8+ T cell killing cells3. Finally, roginolisib augmented the cytotoxicity of chemotherapy and immunotherapy3.

Dostarlimab is a PD-1-blocking antibody approved in the US in combination with chemotherapy for certain patients with endometrial cancer, as well as a single agent for certain patients with dMMR tumours that have progressed on or following prior treatment. It has also demonstrated clinical activity in combination with chemotherapy in NSCLC[4]. Under a supply agreement with iOnctura, GSK will supply dostarlimab for use in the trial. iOnctura will retain worldwide rights to roginolisib.

The Phase I/II open-label, randomized, parallel-arm PULMO-01 study (NCT06879717) will assess roginolisib in combination with dostarlimab, with or without docetaxel. The study will enrol approximately 45 patients who have progressed on standard-of-care immune checkpoint therapy. It will investigate the safety of the combination and the proportion of patients with a reduction in peripheral blood regulatory T cells in each arm.

Roginolisib is an allosteric modulator of PI3Kδ, widely recognized as a ‘master switch’ of cancer. Inhibition of PI3Kδ unleashes a multi-pronged anti-tumor and immune response to combat the tumor[5]. Roginolisib has demonstrated an unprecedented clinical profile in solid and liquid cancers[6], and is currently being investigated in a randomized Phase II clinical trial in uveal melanoma. A separate Phase I/II study in myelofibrosis is being initiated.

On May 8, 2025 TransCode Therapeutics, Inc. (NASDAQ: RNAZ), the RNA oncology company committed to more effectively treating cancer using RNA therapeutics, reported that the third patient in Cohort 4 of its Phase 1a clinical trial has received their initial dose of TTX-MC138 (Press release, TransCode Therapeutics, MAY 8, 2025, View Source [SID1234652781]). All cohorts have enrolled at least three patients who have been dosed with TTX-MC138 at least once. The Safety Review Committee monitoring the clinical trial unanimously approved opening the fourth cohort based on its review of available safety and pharmacokinetic (PK) data. Additionally, the Safety Review Committee approved expanded enrollment in Cohort 3 to obtain additional safety data. To date, 15 patients have received at least one dose of TTX-MC138 at 4 separate dose levels ranging from 0.8 mg/kg to 4.8 mg/kg. Three patients have been treated in the expanded enrollment.

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Ten patients remain on study for continued treatment, receiving an additional dose of TTX-MC138 during each treatment cycle every 28 days, and may remain on study absent any significant safety observations or disease progression. Two patients who have remained on study the longest have received so far seven doses of TTX-MC138 over approximately seven months and have demonstrated stable disease. The 10 patients currently on study have shown no disease progression. Further, no significant safety or dose limiting toxicities have been reported in any of the trial’s 15 patients. Analysis of PK activity from Cohorts 1, 2 and 3 is ongoing and suggests that TTX-MC138 demonstrates a PK/PD profile consistent with preclinical results and results from TransCode’s Phase 0 clinical trial. Specifically, preliminary PK and pharmacodynamic (PD) data follow a predictable dose-response relationship. Analysis of PD activity from cycle 1 treatments in Cohorts 1 and 2, treated with doses of 0.8 mg/kg and 1.6 mg/kg, respectively, demonstrates miR-10b target engagement at 24 hours post-infusion.

The observed tolerability profile and the available PK/PD results thus far support advancement of the clinical trial to further evaluate safety and potential anti-tumor activity of TTX-MC138 in the planned dose expansion (Phase 1b) portion of the trial.

About TTX-MC138

TTX-MC138 is a first-in-class therapeutic candidate designed to inhibit microRNA-10b, or miR-10b, a microRNA widely believed to be critical to the emergence and progression of many metastatic cancers. TransCode’s Phase 0 clinical trial produced evidence of delivery of a radiolabeled version of TTX-MC138 to metastatic lesions and pharmacodynamic activity, even at a microdose of the drug candidate, suggesting a broad therapeutic window for TTX-MC138.

About the Trial

TransCode’s Phase 1 clinical trial is a multicenter, open-label, dose-escalation and dose-expansion study designed to generate critical data to support evaluation of the safety and tolerability of TTX-MC138 in patients with a variety of metastatic solid cancers. While not an endpoint, the trial may provide early evidence of clinical activity of TTX-MC138. The trial comprises an initial dose-escalation stage followed by a dose-expansion stage. The primary objective of the dose-escalation stage is to evaluate the safety and tolerability of escalating dose levels of TTX-MC138. In the dose-expansion stage, the safety, tolerability and anti-tumor activity of TTX-MC138 will be further evaluated in certain tumor types and at a certain dose level selected based on preliminary results from the dose-escalation phase.

Further information is available at www.clinicaltrials.gov NCT Identifier: (NCT06260774).

On May 8, 2025 Whitehawk Therapeutics, Inc. (Nasdaq: WHWK), an oncology therapeutics company applying advanced technologies to established tumor biology to efficiently deliver improved ADC cancer treatments, reported financial results for the first quarter ended March 31, 2025, and provided recent corporate progress (Press release, Whitehawk Therapeutics, MAY 8, 2025, View Source [SID1234652780]).

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"By uniting novel approaches to tumor targeting with next wave technologies, our goal at Whitehawk Therapeutics is to efficiently deliver improved ADC therapies for patients with difficult-to-treat cancers. In the first quarter of 2025, we made meaningful progress in advancing our portfolio toward the clinic and remain on track to bring all three assets to IND by mid-2026, with the first IND filed in Q4 this year," said Dave Lennon, President and CEO of Whitehawk Therapeutics. "Our assets target PTK7, MUC16 and SEZ6 – which we believe have the potential for broad clinical impact comparable to well-established targets like HER2 and TROP2, but with less competition and greater opportunity for differentiation. Coupled with our TOPO1-based leading next wave platform, we are confident in the strength of our strategy and remain committed to advancing with urgency and purpose."

Recent Operational Highlights:

Relaunched as Whitehawk Therapeutics marking evolution into ADC company. Launched with a three-asset portfolio consisting of clinically validated tumor targets that are upregulated in high-potential cancer indications, including lung and ovarian. These assets are engineered to produce minimal off-target toxicity, with a higher therapeutic index and greater stability than first-generation predecessors.
Completed strategic transactions. Closed $100 million PIPE financing and the divestiture of Aadi Subsidiary, Inc. ("Aadi Sub") to Kaken Pharmaceuticals ("Kaken") for $102.4 million, including specified purchase price adjustments. Kaken assumed ownership of Aadi Sub on March 25, 2025, including the Aadi name, trademark and the FYARRO business.
First Quarter 2025 Financial Results:

Cash, cash equivalents and short-term investments as of March 31, 2025, were $231.1 million as compared to $47.2 million as of December 31, 2024.
After completion of transaction-related payments, including the payment of the upfront fees under the Wuxi ADC agreement, we expect to have cash and cash equivalents of approximately $185 million, which we anticipate will fund operations into 2028 based on current plans.
Total revenue for the quarter ended March 31, 2025, was $7.1 million, resulting from sales of FYARRO through March 25, 2025, the closing date of the divestiture to Kaken.
Net income for the three months ended March 31, 2025, was $73.0 million, including a gain of $87.4 million on the sale of Aadi Sub, as compared to a net loss of $18.3 million for the three months ended March 31, 2024. Excluding the gain on the sale of Aadi Sub, net loss for the first quarter of 2025 was $14.4 million.