Committed to Advancing the Understanding of Immunotherapy-Resistant Cancers
and Providing Effective Treatment Solutions to Improve Patient Outcomes
About NEX-I and their Immuno-Oncology
NEX-I is a pioneering biotech headquartered in South Korea, specializing in next-generation cancer therapies with afocus on immunotherapy-resistant cancers. Leveraging its proprietary platform, NEX-I has developed robust models
for immunotherapy-refractory cancers to comprehensively analyze their characteristics and identify novel therapeutictargets. This unique and dedicated research has led to the discovery of a soluble target, ONCOKINE-1 (OK-1), whichhighly expresses and plays a critical role in refractory cellular mechanisms, through ONCOKINE ® screening platform.
Employing this insight, NEX-I developed NXI-101, a treatment designed to inhibit the biological functions of OK-1,
offering a promising new avenue for cancer treatment.
Many companies confirmed their promising anticancer efficacy across various types of traditional animal models, butthey often fail to accurately predict human response to cancer drugs as we face significant percentage of oncology drugs
failing clinical trials today.
NEX-I employed a unique and innovative method by Xsphera Biosciences to predict human response mostaccurately by creating spheroids from fresh human tissue. This system effectively preserves the uniquetumor microenvironment including autologous tumor, immune, and stromal cells of each patient. Please move onto the next paragraph to deepen your understanding of the topic.

NXI-101 Exhibits Potent Anticancer Effects in
the Lung Cancer Patient-Derived ModelHigh Levels of OK-1 Correlated to the HighResponders after NXI-101 Treatment

Freshly isolated cancer tissues from patients with NonSmall Cell Lung Cancer (NSCLC) were placed in a
microfluidic device to establish ex vivo tumor spheroids.
These were then treated with NXI-101, either alone orin combination with an immune checkpoint inhibitor(ICI), for three days. The anticancer effects werequantified by assessing cellular death within the tumor
spheroids. The ratio of dead cell area (identified via
Propidium Iodide staining) to total spheroid area
(identified via Hoechst staining) was calculated forindividual spheroids, and the mean percentage of cell
death across all spheroids was determined. This value wassubsequently normalized to the spheroid's area to yield
the area-weighted percentage of cell death. Notably, in 4
out of 10 NSCLC patient (“High-Responders”) samples(#1, #3, #6, #8), significant increases in cytotoxicity wereobserved with NXI-101 monotherapy or combination
therapy with ICI (Fig. 1), and it was interesting to notethat 3 out of the high-responders were late-stage
NSCLC patients.

To explore the potential of OK-1 levels in tumors as apredictive biomarker for NXI-101 efficacy, we
performed a correlation analysis between OK-1
expression and anticancer effects. The data revealed apositive correlation between OK-1 levels in tumor
tissues and the anticancer effects of NXI-101 (Fig. 2).
Figure 2. Correlation of anticancer efficacy of NXI-101
with OK-1 level in NSCLC Patients (N=10)

Figure 1. Anti-tumor efficacy of NXI-101 in NSCLCPDOTS system (N=10)

1 |PageImmune Signature Changes after NXI-101
Treatment (“High-Responders”)
To investigate the molecular mechanisms underlying
NXI-101'santicancereffects,
weconductedtranscriptomic analyses of treated tumor spheroid
samples using the NanoString nCounter system. In thehigh-responder samples (#1, #3, #6, #8), we observed adecrease in the expression of immune-suppressive
myeloid cell signatures (M-MDSC and M2macrophages) and TGF-β signaling. Concurrently, we
detected an increase in the signatures of cytotoxic
effector cells (CD8+ T cells, NK cells) and tumor
inflammation (Fig. 3). These findings lend support to thehypothesis that the anticancer activity of NXI-101 in
NSCLC is mediated by an enhanced antitumoral
immune response via inhibition of immunesuppressive
mechanisms
withinthetumor
microenvironment.

Conclusion
From “Immune-COLD” to “Immune-HOT”
In summary, NXI-101 exhibited potent anticancer effects
in the NSCLC PDOTS model. Particularly noteworthy isthe enhanced efficacy observed in NSCLC samples
that expressed elevated levels of OK-1. This suggeststhat OK-1 expression could serve as a predictive
biomarker for the effectiveness of NXI-101 in cancertherapy. Additionally, NXI-101 altered the tumor
microenvironment from an "Immune-COLD" to an"Immune-HOT" state, as evidenced by a decrease inimmune-suppressive myeloid cell signatures and anincrease in immune-activating signatures. Theseresults underscore the potential utility of NXI-101 as anovel immuno-oncology therapeutic agent and present it
as a promising candidate for future cancer treatment
regimens.

Figure 3. Immune signatures after NXI-101 treatment in“High-Responders” to NXI-101

First-in-class NXI-101 Summary
Fully human anti-ONCOKINE-1-IgG4S228P mAb✓

ONCOKINE-1 is a novel soluble protein, causing
tumor microenvironment to become resistant against
various I-O therapies✓

Validated predictive and prognostic biomarkers fortreatment response by tissue & blood measurementof ONCOKINE-1✓

Confirmed Efficacy, Safety, and Pharmacokinetics
in pre-clinical study and Ready for an IND
submission by 1H 2024

NEX-I Company Information

Contact Us

For more information, please contact JayJay Jang (Director, Global Business Development) at jayjay@nex-i.co.kr
Office (+82)-2-6951-0412
Web www.nex-i.co.kr
Address A-923 9F, Tera tower 2, 201 Songpa-daero, Songpa-gu, Seoul, 05854, Republic of Korea

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