March 4, 2024

Topline Results of Phase I Clinical Trial of iPS-NKTin Patients with Relapsed or Refractory Head and Neck Cancer
Tokyo, Japan, March 1, 2024/ -- BrightPath Biotherapeutics Co., Ltd. (TSE Growth: 4594), a
clinical- stage biopharmaceutical company focused on developing novel immunotherapeutics,
announce that new first-in-human data from iPS cell-derived NKT cell (“iPS-NKT”, BP2201) being
developed in investigator-initiated Phase I study at Chiba University Hospital demonstrated earlyclinical activity in patients with heavily pretreated relapsed and refractory head and neckcancers. The topline result was presented by Professor Shinichiro Motohashi MD, Ph.D, of Chiba
University, at CD1-MR1 2024 Conference.
The iPS-NKT cell therapy, pioneered by RIKEN and further advanced with the backing of the Japan

Agency for Medical Research and Development (AMED), has been exclusively licensed to BrightPath for
global development, manufacturing, and marketing by RIKEN.

Natural killer T (“NKT”) cells represent a rare subset of T cells that bridges innate and adaptive
immunity, exhibiting diverse anti-tumor effects. Autologous iNKT cell therapy demonstrated
promising outcomes in patients with r/r HNSCC and NSCLC by clinical research at Chiba
University. However clinical-scale manufacturing posed a significant challenges for expanding its
clinical application. The use of induced pluripotent stem (“iPS”) cell technology overcame thehurdle owing to its unparalleled proliferating capacity. The first-in-human Phase I study of theiPS NKT cells has been conducted in patients with r/r HNSCC, with the primary endpoint focusing
on tolerability and safety assessment.
In this study, iPS-NKT cells were administered at a low-dose (3x107cells/m2) and high-dose(1x108cells/ m2) levels, employing multiple dosing regimens. The cells were delivered vja thetumor artery as a monotherapy without prior lymphodepletion, aiming to leverage their uniquecapacity to prime endogenous anti-tumor T cells.
Through the study, the primary endpoint of tolerability and safety was achieved, with the highdose (1x108cells/m2) identified as the Maximum Tolerated Dose (MTD).
The topline summary is as follows.
iPS-NKT cells were administrated to 10 patients: 3 at a low-dose of 3x107cells/ m2 and 7 at ahigh-dose of 1x108cells/ m2. Among them, 6 patients received 3 doses, 3 patients received
two doses, and 1 patient received 1 dose.

While one patient receiving the high dose experienced a drug rash, classified as Dose
Limiting Toxicity (DLT), both the low and high doses were well tolerated.

The most frequently observed treatment-related adverse events (trAEs) were Grade 1 or 2
fever, occurring in 1 patient at the low dose and 4 patients at the high dose1

The change in tumor size in patients who received two or more doses were as follows.

－Low-dose :1 stable disease (SD), 2 progressive disease (PD)－High-dose:

4 stable disease (SD), 1 progressive disease (PD), 1 Not Evaluable

Disease control rate (DCR) 33.3% (1 of 3)
Disease control rate (DCR) 80% (4 of 5 evaluable patients)
Some patients receiving the high dose experienced some level of tendency toward tumor
shrinkage, which has indicated encouraging early clinical activity of iPS-NKT cells.

These initial safety and efficacy findings from the first-in-human study are encouraging andprovide preliminary evidence that employing iPS-NKT as effector cells for a novel allogeneic CART platform could prove to be an effective cancer treatment strategy. Based on these results, weare moving forward with the development of CAR-transduced iPS-NKT cells.

About BrightPath:
BrightPath is a clinical stage biopharmaceutical company focused on the development of novel cancer
immuno-therapies to transform cancer treatment. BrightPath is actively involved in developing celltherapies currently in clinical trials, immunomodulatory antibodies and new cancer vaccine targeting
tumor-specific neoantigens. For more information, visit www.brightpathbio.com/english/index.html
About RIKEN:
RIKEN is Japan’s largest and most comprehensive research organization for basic and applied science anda world leader in a diverse array of scientific disciplines. For nearly a century since its foundation in 1917,
RIKEN has fostered pioneering, innovative research in fields spanning the entire range of the naturalsciences, from developmental biology and neuroscience to quantum physics and computer science.
Today, RIKEN encompasses a network of world-class research centers across Japan, with main campuses inWako, Tsukuba, Yokohama, Kobe and Harima offering state-of-the-art facilities that rank among the best in
the world. This high-quality, high-performance research environment, combined with a uniquely bottomup approach to scientific innovation, has enabled RIKEN to foster an environment in which researchers areable to thrive.
Forward-Looking Statements:
This news release contains forward-looking statements that are based on the current expectations andbeliefs of BrightPath. All statements, other than statements of historical fact, are statements that could be
deemed forward-looking statements. BrightPath cautions that these forward-looking statements do notguarantee our future financial results but involve risks and uncertainties that could cause actual results todiffer materially from those discussed in the forward-looking statements. These forward-lookingstatements speak only as of the date of this press release and BrightPath assumes no duty to update
forward-looking statements, except as may be required by law.
Investor and Media Contact:
irpr@brightpathbio.com
www.brightpathbio.com

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