May 12, 2022

Announcement of the early termination of a phase II clinical trialof the cancer peptide vaccine GRN-1201 in the United States
and Top-line data
Tokyo, Japan - May 12, 2022/ -- BrightPath Biotherapeutics (TSE Growth 4954) announced

that the Company decided to discontinue its Phase II clinical trial of cancer peptide vaccine
GRN-1201 in combination with the anti-PD-1 antibody, pembrolizumab, in patients with
non-small cell lung cancer in the United States. The current key top-line data are reported
in this release.
The study was planned to enroll 64 cases. However, as the global pandemic of COVID19 infection became more serious after 2020, clinical sites shifted medical resources toacute care and outpatient clinics for infectious diseases, and patients hesitated to visit thehospital, resulting in many clinical trials being delayed. In addition, pembrolizumab
monotherapy was the standard therapy for the current study population (non-small cell lungcancer patients with PD-L1 expression in more than 50% of cancer cells: estimated to beabout 20%) when the study was initiated, but at present the combination of pembrolizumab
and chemotherapy has become a major standard therapy for the indication. As a result,patient enrollment has been considerably delayed compared to the original plan, and as ofMay 12, 2022, the cumulative number of patients enrolled in the study was only 20, which
is about 30% of the original plan.
On the other hand, as the study has been conducted for a long term and the clinicalresults could be observed as an open-label study, which enabled us to understand that it
would be difficult to properly evaluate for GRN-1201 using the study protocol originallydesigned.
 The current ORR, the primary endpoint, is comparable to that of single-agent
pembrolizumab, but PFS and OS, which are more appropriate to evaluate the clinicalefficacy, possibly indicate that combination of pembrolizumab and GRN-1201 is
superior to single-agent pembrolizumab.
 Even in non-PR cases, all the three cases evaluated as SD have reached a survival
time of greater than 70 weeks, suggesting durable clinical benefit.
Consequently, OS and/or PFS, not ORR, are considered appropriate as the primary
endpoint.
In addition, the combination of pembrolizumab with chemotherapy is considered the majorstandard therapy for the study indication and does not limit the eligibility to the patients withPD-L1 expression of 50% or higher. Thus, high level PD-L1 expression is no longer needed
to limit the use of GRN-1201.
Thus, we considered that it would be more appropriate to re-plan the endpoints andeligibility requirements and to re-start a study rather than to continue with the current
indication and study protocol.
The combination of pembrolizumab and GRN-1201 did not appear to increase thefrequency of Grade 3 or higher treatment-related AEs compared to pembrolizumab alone
based on published historical data, so it is anticipated that GRN-1201 can be added to theexisting combination therapy of pembrolizumab and chemotherapy or others without any
additional severe trAEs. We believe it is possible to incorporate GRN-1201 into a clinical
trial of various designs.

Top-line data of this clinical trial are as follows.

Assessment of Tumor Size

As of 6 May 2022

Maximum Change from Baseline (%)

40.0(n=16*)

20.0
4.0
0.0-4.0-6.7

-7.8

-20.0

-20.4

-22.8

-40.0

-40.2
-47.3

-60.0

-50.0

-50.0

-54.8

-56.5

-59.4

-63.8

-80.0

-69.4
-81.9

-100.0Best Response

PDSDSDSD

SD

SD

PR

PR

PR

PR

PR

PR

PR

PR

PR

PR

Overall Response

PDNE

SD

SD

SD

PD

PR

NE

PR

PD

PR

NE

PR

PR

PR

PR

* This analysis was performed using the data from patients who have at least one post-baseline imaging evaluation for tumor response

Progression Free Survival
1,2,3

Pembro-monotherapy Keynote-024 *Pembro-monotherapy Keynote-042 *4,5GRN-1201 +Pembro
TPS ≥ 50% for Keynote-042

PFSMedian (M)12M PFS Rate

Number ofsubjects

Number ofevents(%)

7.7
7.1
22.5

48%
37%
62%

15429919126 (82%)
221(74%)8 (42%)

Overall Survival
Pembro-monotherapy Keynote-024 *Pembro-monotherapy Keynote-042 *GRN-1201 + Pembro
TPS ≥ 50% for Keynote-042

1,2,3
4,5

OSMedian (M)26.3
20
Not reached

12M
Survival Rate

24M
Survival Rate

Number ofsubjects

Number ofevents(%)

70%
64%
75%

52%
45%
64%

15429919103 (67%)
157 (53%)
5 (26%)

Reference:*1 J Clin Oncol, 2021 Jul 20;39(21):2339-2349*2 J Clin Oncol, 2019 Mar 1;37(7):537-546*3 NICE; Pembrolizumab for untreated PD-L1 positive metastatic non-small-cell lung cancer [ID990] Committee Papers*4 Lancet, 2019 May 4;393(10183):1819-1830*5 MSD K.K.

Safety and Tolerability
 No major safety issues••

GRN-1201 in combination with pembrolizumab did not appear to increase thenumber of patients experiencing > Grade 3 treatment-related adverse events
relative to pembrolizumab as a single agent.
No patient discontinued due to GRN-1201-related adverse events.About BrightPath:
BrightPath Biotherapeutics is a clinical-stage biopharmaceutical company focused on
immuno-oncology and dedicated to improving treatment and clinical outcomes for patients
through cancer vaccine, therapeutic antibodies, and cell therapy that harness the immune
system to fight cancer.
BrightPath’s clinical-stage products include iPS-NKT(unmodified induced pluripotent stem cellderived NKT therapy), BP2301(HER2-targeted CAR-T) and GRN-1201(four shared tumor
associated antigen-based peptide cancer vaccine).
BrightPath has several potentially first-in-class and best-in-class preclinical candidates in
immunomodulatory antibodies and a novel personalized neoantigen vaccine platform.
For more information, visit https://www.brightpathbio.com/english/index.html
Forward-Looking Statements:
This news release contains forward-looking statements that are based on the current
expectations and beliefs of BrightPath. All statements, other than statements of historical fact,
are statements that could be deemed forward-looking statements. BrightPath cautions thatthese forward-looking statements do not guarantee our future financial results but involve risks
and uncertainties that could cause actual results to differ materially from those discussed in theforward-looking statements. These forward-looking statements speak only as of the date of thispress release and BrightPath assumes no duty to update forward-looking statements, except as
may be required by law.

Investor and Media Contact:
Director of Corporate Management
irpr@brightpathbio.com
www.brightpathbio.com