Dear Colleagues and Friends,
The Year of the Horse symbolizes strength, endurance, coordinated momentum, and the courage to move first. At SparX, that spirit perfectly reflects how we are approaching one of oncology’s most urgent challenges: overcoming resistance biology in the post-Enhertu era.
This year, we celebrate not just tradition — but convergence!
At SparX, two therapeutic “horses” are running in tandem toward a shared mission: redefining how we treat cold and refractory tumors.
The first horse is AiPRiSM™, our programmable dual-payload ADC architecture. Rather than incremental cytotoxic escalation, AiPRiSM™ delivers mechanistic orthogonality within a single molecule — combining topoisomerase-I–mediated DNA damage with site-specific, sterically shielded MMAE microtubule disruption. This architecture is designed not only to kill, but to induce immunogenic cell death, amplify antigen release, and expand the therapeutic window through precise DAR control and industrialized conjugation.
The second horse is SPX-303, our first-in-class LILRB2 × PD-L1 bispecific. While traditional checkpoint inhibitors focus on T cells alone, SPX-303 simultaneously reprograms suppressive myeloid cells and restores cytotoxic T-cell activity. By converting M2 macrophages to an M1 phenotype and breaking the myeloid shield, SPX-303 unlocks immune infiltration in tumors previously considered “cold.”
Individually, each platform is powerful. Together, they create a high-symmetry therapeutic strategy:
The dual-payload ADC primes the tumor microenvironment through DNA damage, mitotic disruption, and DAMP release. SPX-303 then unlocks T-cell attack by removing macrophage suppression and PD-L1–mediated inhibition. ADC ignites the spark → SPX-303 sustains the immune assault.
This convergent approach is not theoretical:
SPX-629, our HER2 dual-payload ADC, has demonstrated tumor control at 3 mg/kg where Enhertu® progressed, with a >10-fold therapeutic window in cynomolgus studies. SPX-303 has shown visible tumor regression after a single 30 mg/kg Q2W dose in a heavily pretreated, anti-PD-1-refractory HNSCC patient — a population with no approved effective options.
Across additional programs including SPX-602 and SPX-608, we continue to validate that architecture — not simply payload — determines durability, tolerability, and resistance control.
We believe the next era of ADCs will not be defined by higher potency alone, but by intelligent molecular design, programmable stoichiometry, and immune convergence. As outlined in our recent platform presentation, SparX is building not just molecules, but an industrial architecture enabling reproducible DAR control, continuous-flow conjugation, and scalable high-DAR stabilization to support global development
The Year of the Horse reminds us that coordinated strength moves farther than isolated speed.
Our dual-payload ADCs and SPX-303 are not competing strategies — they are companions, each amplifying the other’s impact. To our collaborators, investigators, investors, and fellow innovators — thank you for running alongside us. Here’s to a year of strength, endurance, and breakthrough progress for patients who need it most.
恭喜发财.
Wishing you joy, prosperity, and unstoppable momentum!
Gui-Dong
