# A novel MICA/B based tumor-centric bispecific antibody that enhances NK cell activity in a hostile tumor microenvironment

> **NIH NIH R43** · AAKHA BIOLOGICS INC. · 2024 · $400,000

## Abstract

PROJECT SUMMARY/ABSTRACT
Problem: Lung cancer is the third most common cancer in the US, with an estimated 238,340 new cases in
2023, and is projected to be about 2.5 times more deadly than any other cancer type in 2023 (127,070 deaths).
The 5-year survival rate for advanced metastatic lung cancer is only 7%. There is a huge unmet medical need
for treatment of patients that are resistant or refractory to targeted therapies or recently approved immune check
point inhibitors. There is very strong evidence that higher levels of soluble MICA and MICB cleaved from the
cancer cell surface led to immune escape and directly correlated with a poor patient survival rate. Therefore,
designing an antibody-based therapy that blocks MICA/B cleavage presents an attractive therapeutic
opportunity. Technology: Aakha Biologics is developing a novel first-in-class MICA X MSLN bispecific antibody
for the treatment of advanced metastatic lung cancer that is resistant or refractory to current treatment options.
The MICA X MSLN bispecific antibody combines three crucial components into a single agent, bringing synergy
in NK cell activation: (I) an anti-α3 domain-specific MICA/B binding arm to block proteolytic cleavage of MICA/B
and restore immune surveillance by re-engaging MICA/B (via the α1 and α2 MICA domains) with NKG2D, (II) an
engineered Fc variant to enhance ADCC activity compared to WT Fc, and (III) an anti-MSLN binding arm to
enhance specificity and efficacy. Aakha Biologics has identified an ADCC enhanced Fc engineered lead anti-
MICA antibody (AHA-1031) that prevents shedding of MICA/B. We demonstrated that our Fc engineered
antibody dramatically slows and inhibits tumor growth compared to the benchmark CLN-619 antibody that is in
a Phase 1 clinical trial. To further boost efficacy and specificity, we constructed a tool bispecific antibody that
comprises our lead anti-MICA Fab arm as the immune activating arm, an anti-MSLN sdAb (from the literature)
as the TAA arm, and an enhanced ADCC Fc variant. As expected, we observed much higher specific cell killing
for the bispecific antibody compared to the monoclonal parent antibody. With this knowledge, we now plan to
assemble our own ADCC-enhanced bispecific MICA X MSLN antibody. The goal of the current proposal is to
screen and identify the best bispecific antibody that demonstrates superior tumor growth inhibition in multiple
NSCLC mouse tumor models compared to benchmark antibodies. Successful completion of the proposed
studies will support a Phase II SBIR application and help us complete a portion of the IND-enabling studies. Our
final goal is to take this bispecific antibody into clinical trials and potentially provide improved treatment options
for patients with advanced NSCLC.

## Key facts

- **NIH application ID:** 10821069
- **Project number:** 1R43CA287713-01
- **Recipient organization:** AAKHA BIOLOGICS INC.
- **Principal Investigator:** hemanta baruah
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $400,000
- **Award type:** 1
- **Project period:** 2024-05-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10821069

## Citation

> US National Institutes of Health, RePORTER application 10821069, A novel MICA/B based tumor-centric bispecific antibody that enhances NK cell activity in a hostile tumor microenvironment (1R43CA287713-01). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10821069. Licensed CC0.

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