On April 23, 2026 CREATE Medicines, Inc., ("CREATE"), a clinical-stage biotechnology company pioneering in vivo immune cell programming, reported the dosing of the first patient in the Phase 1/2 clinical trial of MT-304, an investigational in vivo HER2-targeted multi-immune CAR therapy. The study is evaluating MT-304 in patients with HER2-positive breast cancer and other HER2-positive solid tumors, including gastric cancer. MT-304 is the first of CREATE’s multi-immune in vivo CAR therapies to enter clinical development and represents an important step in expanding the company’s platform into NK and T cells.

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"HER2-positive cancers remain an area of high unmet need for patients whose disease has progressed on available targeted therapies," said Matthew Maurer, M.D., Chief Medical Officer of CREATE. "Dosing the first patient with MT-304 reflects our ability to rapidly iterate on our mRNA-LNP platform to meet the clinical urgency. We are now engaging multiple arms of immunity simultaneously, an approach we believe can unlock durable responses where single lineage therapies have fallen short."

"Patients with HER2-positive cancers who have progressed beyond current options have very few paths forward," said Dr. Jordan Cohen, Medical Oncologist and Principal Investigator, Calvary Mater Newcastle, NSW, Australia. "Engaging both NK and myeloid cells simultaneously to coordinate multiple arms of the immune system to attack at the same time has not been possible in the clinic before now. That makes MT-304 both scientifically compelling and potentially meaningful for the patients who need it most."

Daniel Getts, Ph.D., CEO of CREATE, added "MT-304 is proof of what our platform can do, and what our team can execute. Our mRNA-LNP leadership enables us to move from concept to clinic with remarkable speed. Just last weekend at AACR (Free AACR Whitepaper), we presented compelling preclinical data across our in vivo CAR T, CAR NK, and CAR myeloid programs, and introduced RetroT, our all-RNA genome integration platform for stable, durable cell engineering without viral vectors. Both are on track to enter the clinic within 12 months, highlighting a platform designed to consistently convert innovation into clinical outcomes."

About MT-304

MT-304 is an investigational in vivo HER2-targeted NKp44-CAR therapy that programs NK and myeloid cells using CREATE’s redosable mRNA-LNP system. MT-304 is designed to produce:

CAR expression in NK and myeloid cells through DAP12-mediated signaling
Potent NK-mediated tumor lysis and myeloid-driven tumor remodeling
Enhanced antigen spreading and coordination of adaptive immunity
Repeat-dose capability with sustained pharmacodynamic activity, requiring no lymphodepletion or ex vivo manufacturing
HER2 is highly expressed across a majority of HER2-positive breast and gastric cancers and represents an established oncology target. Preclinical data demonstrate superior activity over CD89-based CAR constructs, tumor regression in models refractory to CAR T and checkpoint inhibitors, enhanced immune infiltration, and durable tumor clearance through combined NK and myeloid programming.

About the Phase 1/2 Study of MT-304

The Phase 1/2 clinical study (ClinicalTrials.gov Identifier: NCT07334119) is a multi-center, open-label, dose-escalation trial evaluating MT-304 in adults with HER2-positive breast cancer and HER2-positive solid tumors. The study will assess safety, tolerability, pharmacokinetics, pharmacodynamics, CAR expression kinetics, immune activation, and preliminary antitumor activity. Data generated from this trial will inform recommended Phase 2 dose selection, expansion cohorts, and broader clinical development strategies.

About HER2-Positive Cancer

HER2-positive cancers arise from overexpression of the epidermal growth factor receptor HER2, driving aggressive tumor growth. While targeted therapies have improved outcomes, many patients relapse, and limited durability of response and eventual resistance remain major challenges. HER2-positive breast cancer remains a significant cause of global cancer mortality, and HER2-positive gastric and other solid tumors present additional therapeutic challenges. Novel treatment modalities capable of delivering durable, multi-lineage immune activation are urgently needed. By unlocking coordinated immune activation through NK and myeloid programming, MT-304 aims to offer a new therapeutic paradigm that may overcome resistance patterns and deliver more sustained disease control.

(Press release, Create Medicines, APR 23, 2026, View Source [SID1234664730])