Biointron’s Lunch & Learn with MassBio was held in Boston, MA, on May 9. The session focused on the advancements in antibody discovery in the biopharma industry and featured three key speakers: Dr. Hitesh Soni (Director of In Vivo Pharmacology at Tectonic Therapeutic Inc.), Dr. Lei Shi. (SVP at Biointron), and Dr. Qiming Wang (Director of Product Strategy & Strategic Partnerships at Cyagen). We thoroughly enjoyed hosting the event and the audience’s strong engagement!
Dr. Lei Shi: Advancing Antibody Discovery: Innovations, Trends, and Industry Insights
Biointron’s SVP, Dr. Shi, welcomed the session with a presentation on accelerating antibody discovery and development with Biointron’s high-throughput platforms. Cases discussed include:
- The successful production of 818 IgGs through development of a panel of positive antibodies within two weeks.
- An alpaca VHH discovery case and construction of a bispecific antibody targeting a cell surface receptor expressed on T cells. VHH antibodies can be used in a range of therapeutics including bispecific, multispecific, conjugate, CAR-T, and nanoparticle drug delivery.
- Our AbDrop Antibody Discovery Platform from Single B Cells based on microfluidics technology.
Dr. Qiming Wang: Accelerating Antibody Discovery with Fully Human Antibody Mouse HUGO-AbⓇ and Single B Cell Screening Technology AbDropⓇ
The Director of Product Strategy & Strategic Partnerships at Cyagen began with an introduction of Cyagen’s transgenic mouse technology and Biointron’s expertise in antibody discovery and expression, eventually translating into therapeutic antibodies benefit human health.
1. The HUGO-Ab® Platform: A Fully Human Antibody Mouse
The HUGO-Ab® mouse model is engineered with human heavy and light chain genes (IGHV, IGKV, IGLV) to generate diverse, fully human antibodies.
It mimics normal B cell development and produces IgG levels comparable to wild-type C57BL/6 mice.
Heavy and light chain germline diversity matches human frequencies, maximizing therapeutic mAb discovery potential. The immunization protocol spans 60 days and includes four boosts, followed by B cell collection for antibody screening.
2. Application: Anti-PD-L1 Antibody Discovery
HUGO-Ab® mice were used to generate anti-PD-L1 antibodies and benchmarked against Atezolizumab
Case Study: HUGO-427 clone yielded 0.5% positive droplets vs. 0.3% from wild-type C57.
EC50 analysis showed 3 HUGO-427 molecules with stronger activity than the benchmark, versus 2 in WT-C57.
Affinity rates were comparable (78.9% vs. 85%), but both groups yielded high-affinity functional antibodies.
AbDrop® enabled rapid, single B cell-based discovery with detailed binding and blocking assays.
3. Case Studies Highlighting Platform Efficiency
VEGF165 Discovery: Using HUGO-Ab®, 13/20 antibodies showed sub-nanomolar affinity.
Hybridoma Comparison: For a target 90% similar to mouse protein, AbDrop® + HUGO-Ab® produced 28 binders, compared to 2 from hybridoma alone.
4. Expansion: HUGO-Light and HUGO-Nano Platforms
HUGO-Light: Features fixed human light chains with natural VH/Vκ usage patterns. Efficient in generating high-affinity anti-VEGF antibodies via single B cell sorting.
HUGO-Nano: Focuses on fully human nanobody generation with applications in bispecifics, ADCs, and CAR-Ts. Offers low immunogenicity and cost-effective development.
5. Competitive Advantages and Ecosystem Integration
Cyagen’s antibody discovery ecosystem integrates:
AI-driven humanness scoring (trained on 1B+ antibody sequences)
Flexible licensing and service models
Global infrastructure across the US, China, and Japan
Dr. Hitesh Soni: TX000045 (TX45), a Novel Fc-Relaxin-2 Fusion Protein: Bioengineering and Preclinical Development for the Treatment of Group 2 Pulmonary Hypertension (PH)
The Director of In Vivo Pharmacology at Tectonic Therapeutic Inc. began with a quote from Sir William Osler, “The good physician treats the disease; the great physician treats the patient who has the disease.”
1. Rationale and Mechanism of Action
Relaxin, a natural ligand of the RXFP1 receptor, is known for its vasodilatory and antifibrotic roles during pregnancy. It acts without inducing receptor internalization, avoiding desensitization even with chronic administration. TX45 leverages these properties to address the pathophysiology of Group 2 PH, which involves vascular remodeling, inflammation, and increased pulmonary pressure.
2. Clinical Precedent and Need for Innovation
Previous trials with Serelaxin showed promise:
Phase 2 trials demonstrated improved dyspnea and reduced pulmonary artery pressure.
Phase 3 trials (RELAX-AHF-2) failed to meet primary endpoints but showed reduced early heart failure events.
These results highlighted the therapeutic potential of Relaxin but also emphasized the need for molecules with improved pharmacokinetics (PK) and pharmacodynamics (PD).
3. Bioengineering Strategy to Improve PK
Earlier Fc-Relaxin fusions like TX-04 and RELAX0010 had poor PK profiles, characterized by rapid α-phase declines.
TX45 was designed with a reduced isoelectric point (pI), leading to significantly improved PK compared to high-pI molecules.
Though in vitro potency (EC₅₀ = 30 nM) was slightly reduced, TX45 showed better in vivo performance.
4. Preclinical Pharmacodynamics and Efficacy
TX45 outperformed comparators in the rat renal arterial blood flow (RABF) model:
At equivalent doses, TX45 produced significantly greater renal vasodilation than high-pI comparators.
Demonstrated a strong dose-response relationship aligning with in vitro potency (in vivo EC₅₀ = 34 nM).
5. Disease Model Results: Monocrotaline-Induced PH in Rats
In a preclinical model of PH:
TX45 prevented MCT-induced mortality and significantly reduced right ventricular (RV) hypertrophy.
Improved pulmonary hemodynamics (lower RV systolic pressure and mean PAP).
Reduced lung inflammation and muscularization of pulmonary arterioles.
6. Conclusion and Future Outlook
TX45 represents a transformative therapeutic candidate for Group 2 PH:
Combines the biological advantages of Relaxin with enhanced drug-like properties.
Demonstrated safety, strong PK/PD correlation, and robust efficacy in disease models.
Positioned to advance toward clinical trials with potential to improve survival and quality of life in PH patients.
Afterwards, we held our raffle where our lucky winners received an Apple iPad, Google Nests, and tumblers!
Thank you to everyone who joined us at MassBio! We had a fantastic time connecting with you and sharing how we can help you achieve antibody development. Our expert team would be happy to answer any follow-up questions. Feel free to email us at info@biointron.com or visit our website at www.biointron.com.