On December 17, 2025 Circle Pharma, Inc., a clinical-stage biopharmaceutical company pioneering next-generation targeted macrocycle therapeutics for cancer, reported the nomination of CID-165, a first-in-class, orally bioavailable macrocyclic cyclin D1 RxL inhibitor, as the development candidate for its second oncology program.

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!

Cyclin D1 is a regulatory protein that plays a crucial role in cell cycle progression and is overexpressed or translocated in malignancies, including ER-positive breast cancer and lymphomas. In these cancers, cyclin D1 drives cell proliferation by binding to the tumor suppressor retinoblastoma protein (Rb) leading to uncontrolled cell division. In preclinical studies, CID-165 has been shown to potently and selectively disrupt the cyclin D1-Rb interaction allowing Rb to remain active and suppress cancer cell proliferation. CID-165 demonstrates robust anti-tumor activity in cyclin D1-driven preclinical cancer models including in combination with other therapies such as CDK4/6-dual inhibitors, CDK4-selective inhibitors, and endocrine therapies.

"Cyclin D1 has long been recognized as a key oncogenic driver across many solid tumors and hematologic malignancies, yet it has remained an elusive direct therapeutic target," said Marie Evangelista, Ph.D., senior vice president and head of cancer biology at Circle Pharma. "Our MXMO platform has allowed us to design a novel macrocyclic molecule, CID-165, with the precision and selectivity needed to directly block cyclin D1-Rb signaling while minimizing effects on related cyclins, such as cyclin D3, an approach aimed at reducing side effects commonly observed with dual CDK4/6 inhibitors."

"Despite the transformative impact of CDK4/6 inhibitors for the treatment of ER-positive breast cancer, many patients eventually experience disease progression or adverse events that impact their quality of life," said Anne Borgman, M.D., chief medical officer of Circle Pharma. "CID-165 is designed to address these limitations through selective inhibition of cyclin D1, a central driver of tumor proliferation, while avoiding adverse events associated with broader CDK4/6 blockade. We look forward to advancing CID-165 toward IND submission in late 2026 and potentially translating the compelling preclinical activity into benefit for patients."

(Press release, Circle Pharma, DEC 17, 2025, View Source [SID1234661500])

On December 17, 2025 Biomea Fusion, Inc. ("Biomea") (Nasdaq: BMEA), a clinical-stage diabetes and obesity company, reported that Mick Hitchcock, Ph.D., Interim Chief Executive Officer and Board Member, will present at the 44th Annual J.P. Morgan Healthcare Conference on Wednesday, January 14, 2026 from 5:15 PM to 5:55 PM Pacific Time. Additionally, Biomea’s management team will host one-on-one meetings throughout the conference, which will take place from January 12-15.

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 live audio webcast of the presentation can be accessed here or by visiting the Investors & Media section of Biomea’s website at View Source A replay of the webcast will be available following the live presentation.

(Press release, Biomea Fusion, DEC 17, 2025, View Source [SID1234661499])

On December 17, 2025 HUTCHMED (China) Limited ("HUTCHMED") (Nasdaq/AIM:​HCM; HKEX:​13) reported the initiation of its global Phase I clinical development program for HMPL-A251, a first-in-class PI3K/PIKK-HER2 Antibody-Targeted Therapy Conjugate ("ATTC") comprising a highly selective and potent PI3K/PIKK inhibitor payload conjugated to a humanized anti-HER2 IgG1 antibody via a cleavable linker. Study sites are in the US and China. The first patient received the first dose on December 16, 2025, in China.

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 first-in-human Phase I/IIa, open-label, multicenter clinical study evaluates HMPL-A251 monotherapy in adult patients with unresectable, advanced or metastatic HER2-expressing solid tumors. The study is divided into two parts, a Phase I dose escalation part and a Phase IIa dose expansion and optimization part. The primary outcome measures are to evaluate the safety and tolerability of HMPL-A251 and to determine the maximum tolerated dose (MTD) and/or recommended dose(s) for expansion ("RDE") in the Phase I part, and to further evaluate safety and preliminary efficacy at RDEs and to determine the recommended dose for Phase II (RP2D) or Phase III (RP3D) in the Phase IIa part. Secondary outcome measures include preliminary antitumor activity, pharmacokinetic profile, and the immunogenicity of HMPL-A251. Additional details may be found at clinicaltrials.gov, using identifier NCT07228247.

HMPL-A251 is the first clinical-stage candidate derived from HUTCHMED’s next-generation ATTC platform. The first family of programs are based on a highly potent and selective PI3K/PIKK inhibitor payload. By conjugating this highly novel payload to an anti-HER2 antibody, the molecule is designed to deliver targeted pathway inhibition directly into HER2-expressing tumor cells, thereby potentially overcoming the systemic toxicity and narrow therapeutic index historically associated with PI3K/PIKK inhibitors. This approach aims to achieve deeper and more durable target inhibition while improving the overall tolerability profile.

Preclinical data for HMPL-A251 were presented at the 2025 AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper). This body of evidence supports the translational potential of the ATTC platform, the ongoing global clinical evaluation of HMPL-A251, and the broad potential of HUTCHMED’s PI3K/PIKK inhibitor linker-payload to underpin a family of future ATTC drug candidates.

About the ATTC Platform
HUTCHMED’s ATTC platform represents a next-generation approach to precision oncology, combining monoclonal antibodies with proprietary small-molecule inhibitor payloads to deliver dual mechanisms of action. Unlike traditional cytotoxin-based Antibody Drug Conjugates, ATTCs combine targeted therapies to achieve synergistic anti-tumor activity and durable responses in preclinical models, outperforming standalone antibody or small-molecule inhibitor components in efficacy and safety.

Built on over 20 years of targeted therapy expertise, the platform enables development of drug candidates for diverse cancer types. By leveraging antibody-guided delivery and tumor-specific payload release, ATTCs improve the accessibility to tumors and reduce off-tumor toxicity. This overcomes challenges of traditional small-molecule inhibitors, ensures safer long-term use, and supports combinations with chemotherapy and immunotherapy, unlocking potential for early-line treatments.

About the PAM Pathway and HMPL-A251
The PI3K/AKT/mTOR ("PAM") pathway is a critical intracellular network involved in cell growth, survival, and division. Alterations in the PAM pathway are frequently associated with poor prognosis and resistance to treatment across various cancers. However, existing PAM-targeted drugs face significant challenges, including on-target toxicities that restrict dosing, feedback loops that enable pathway reactivation, and insufficient tumor-specific delivery. HUTCHMED has designed a highly novel PI3K/PIKK inhibitor linker-payload to overcome these challenges with broad potential to lead to a family of antibody conjugate drug candidates.

HMPL-A251 is a first-in-class ATTC comprising of this highly selective and potent PI3K/PIKK inhibitor payload conjugated to a humanized anti-HER2 IgG1 antibody via a cleavable linker, designed to address challenges by enhancing targeted delivery directly to tumor cells, maximizing therapeutic benefit while minimizing systemic exposure. In preclinical studies, the HMPL-A251 payload exhibited high selectivity, potency, and robust anti-tumor activity. HMPL-A251 exhibited superior anti-tumor efficacy and tolerability compared to co-administration of the naked antibody and payload.

(Press release, Hutchison China MediTech, DEC 17, 2025, View Source [SID1234661460])

On December 16, 2025 Tubulis reported that its CEO and Co-founder Dominik Schumacher will present a company overview and update at the 44th Annual J.P. Morgan Healthcare Conference in San Francisco.

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!

The presentation will take place on Monday, January 12, 2026, at 3:00 pm PT in the Mission Bay Room (32nd Floor) at The Westin St. Francis.

(Press release, Tubulis, DEC 16, 2025, View Source [SID1234661475])

On December 16, 2025 Vyriad, Inc., a clinical-stage biotechnology company developing targeted genetic therapies for cancer and other serious diseases, reported detailed data on its lentiviral vector retargeting technologies and its lead therapeutic in vivo chimeric antigen receptor (CAR) T program, VV169, at the recently concluded 67th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting.

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!

The first poster detailed the company’s three in vivo T-cell-targeted delivery systems, the first of which will soon be tested clinically through the VV169 program in a U.S.-based clinical trial in patients with multiple myeloma. The second poster presented strong preclinical data for VV169 that supports its progression into clinical development. The therapy achieved a durable complete resolution of disease in mice with disseminated myeloma at all doses, including the lowest level.

"While we have recently seen remarkable proof-of-concept for in vivo CAR T in heavily pretreated multiple myeloma, the next hurdle is eliminating infusional toxicities, so that we can truly unlock the promise of this modality," said Stephen Russell, M.D., Ph.D., CEO of Vyriad. "Our singular focus is solving this technology challenge, and the data presented at ASH (Free ASH Whitepaper) demonstrate Vyriad’s strong and rapid progress. We are advancing our vectors’ targeting, transduction and safety capabilities to ensure this new generation of in vivo CAR T therapies carries the field’s momentum forward."

While recent breakthroughs have validated in vivo CAR T as a scalable alternative to complex ex vivo therapies, Vyriad sees an opportunity to optimize the modality for broad clinical use. Leveraging its deep expertise in virology and oncolytic viruses, the company has developed a proprietary platform anchored in advanced G protein engineering, yielding lentiviral vectors with high serum stability and enhanced transduction efficiency — key requirements for safe, precise, and low-dose in vivo gene delivery.

Evaluation of three in vivo targeting approaches

Vyriad has developed three distinct retargeting strategies to selectively transduce resting T cells in the lymphoid niche. This effort is part of the company’s ongoing pursuit of improving lentiviral vector targeting not only for precise and safe delivery, but also to streamline manufacturing and development even further. The three methods are:

Direct Covalent Display: This approach uses a chimeric VSV-G protein that displays a CD3-targeting ligand but is modified to blind its natural interaction with the low-density lipoprotein (LDL) receptor. This method was then applied to retarget the LV169 vector used in the VV169 program, enabling precise T-cell targeting for in vivo CAR T delivery.
Trimeric Adapter Proteins: A protein adapter is used to "cap" the unmodified VSV-G trimer and redirect it to CD3 while masking its ability to bind to natural receptors. This was achieved by mixing a conventional lentiviral vector with trimeric adapter proteins. The association between the G protein trimer and the trimeric cap remained highly stable during freeze-thaw cycles and at room temperature, underscoring its viability as an in vivo targeting platform.
Modular Covalent Display: SPY-tagged VSV-G proteins are covalently modified by mixing them with a SPY-catcher/CD3 ligand fusion protein at room temperature, which spontaneously binds SPY-tag, thereby redirecting entry to the SPY-catcher targeting ligand.
The direct covalent display method is currently undergoing clinical translation through VV169. Manufacturing studies for all three targeting approaches are currently underway.

Lead in vivo CAR T candidate VV169

VV169 is designed as a single intravenous administration of a B-cell maturation antigen (BCMA)-targeted CAR transgene, delivered by the LV-169 lentiviral vector. The second poster presented at ASH (Free ASH Whitepaper) 2025 details the complete elimination of disseminated multiple myeloma in humanized mouse models.

Key highlights of the data include:

100% of mice treated with a single intravenous injection of therapy cleared OPM-2 tumors completely within 28 days. This response held true for all dose levels, including the lowest dose tested. The mice remained tumor-free 84 days post-treatment and successfully resisted tumor re-challenge.
The treatment was well tolerated. Analysis of cytokines confirmed the absence of a severe cytokine storm. While IFNγ was elevated during T-cell expansion, inflammatory markers, such as IL-6, TNFα and GM-CSF, were barely detectable.
The use of a T-cell-specific promoter prevented CAR protein from being expressed on the virus particle itself, minimizing off-target gene delivery to myeloma cells
Vyriad is continuing preclinical work for the development of VV169 and plans to begin a clinical trial in the U.S. in 2026.

(Press release, Vyriad, DEC 16, 2025, View Source [SID1234661474])