{"id":3908,"date":"2026-02-16T07:47:06","date_gmt":"2026-02-16T07:47:06","guid":{"rendered":"\/?p=3908"},"modified":"2026-02-16T07:48:04","modified_gmt":"2026-02-16T07:48:04","slug":"happy-lunar-year-of-the-horse-two-horses-one-mission","status":"publish","type":"post","link":"\/?p=3908","title":{"rendered":"Happy Lunar Year of the Horse \u2014 Two Horses, One Mission"},"content":{"rendered":"
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Dear Colleagues and Friends,<\/p>\n\n\n\n

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\u2019s most urgent challenges: overcoming resistance biology in the post-Enhertu era.<\/p>\n\n\n\n

This year, we celebrate not just tradition \u2014 but convergence!<\/p>\n\n\n\n

At SparX, two therapeutic \u201chorses\u201d are running in tandem toward a shared mission: redefining how we treat cold and refractory tumors.<\/p>\n\n\n\n

The first horse is AiPRiSM\u2122<\/strong>, our programmable dual-payload ADC architecture. Rather than incremental cytotoxic escalation, AiPRiSM\u2122 delivers mechanistic orthogonality within a single molecule \u2014 combining topoisomerase-I\u2013mediated 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.<\/p>\n\n\n\n

The second horse is SPX-303<\/strong>, our first-in-class LILRB2 \u00d7 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 \u201ccold.\u201d<\/p>\n\n\n\n

Individually, each platform is powerful. Together, they create a high-symmetry therapeutic strategy:<\/p>\n\n\n\n

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\u2013mediated inhibition. ADC ignites the spark \u2192 SPX-303 sustains the immune assault.<\/p>\n\n\n\n

This convergent approach is not theoretical:<\/p>\n\n\n\n

SPX-629, our HER2 dual-payload ADC, has demonstrated tumor control at 3 mg\/kg where Enhertu\u00ae 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 \u2014 a population with no approved effective options.<\/p>\n\n\n\n

Across additional programs including SPX-602 and SPX-608, we continue to validate that architecture \u2014 not simply payload \u2014 determines durability, tolerability, and resistance control.<\/p>\n\n\n\n

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 <\/p>\n\n\n\n

The Year of the Horse reminds us that coordinated strength moves farther than isolated speed.<\/p>\n\n\n\n

Our dual-payload ADCs and SPX-303 are not competing strategies \u2014 they are companions, each amplifying the other\u2019s impact. To our collaborators, investigators, investors, and fellow innovators \u2014 thank you for running alongside us. Here\u2019s to a year of strength, endurance, and breakthrough progress for patients who need it most.<\/p>\n\n\n\n

\u606d\u559c\u53d1\u8d22.
Wishing you joy, prosperity, and unstoppable momentum!<\/p>\n\n\n\n

Gui-Dong<\/p>\n","protected":false},"excerpt":{"rendered":"

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\u2019s most urgent challenges: overcoming resistance biology in the post-Enhertu era. This year, we celebrate not just tradition \u2014 but convergence! At SparX, […]<\/p>\n","protected":false},"author":1,"featured_media":3905,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":[],"categories":[40],"tags":[],"_links":{"self":[{"href":"\/index.php?rest_route=\/wp\/v2\/posts\/3908"}],"collection":[{"href":"\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=3908"}],"version-history":[{"count":3,"href":"\/index.php?rest_route=\/wp\/v2\/posts\/3908\/revisions"}],"predecessor-version":[{"id":3911,"href":"\/index.php?rest_route=\/wp\/v2\/posts\/3908\/revisions\/3911"}],"wp:featuredmedia":[{"embeddable":true,"href":"\/index.php?rest_route=\/wp\/v2\/media\/3905"}],"wp:attachment":[{"href":"\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=3908"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=3908"},{"taxonomy":"post_tag","embeddable":true,"href":"\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=3908"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}