Four years ago to the day, we started Orchestra Bio to help biotech and pharma teams advance their drug development programs. AI has now reached an inflection point where people and agents can take this on together. Today, we’re thrilled to share that Orchestra Bio is joining OpenAI to continue our mission at an even greater scale.

What happens to the gut when we profoundly eliminate the B-cell compartment? CAR-T therapy has transformed multiple myeloma, but as BCMA-directed therapies expand, we are beginning to see consequences beyond the tumor. A new study characterizes CAR-T cell-induced enterocolitis (CAR-TEC) after cilta-cel and provides a striking look at what may be happening within the intestinal mucosa. Using single-cell transcriptomics, flow cytometry, and tissue imaging of intestinal biopsies, investigators compared patients with CAR-TEC, CAR-T–treated patients without enterocolitis, and healthy volunteers. They found a remarkably disrupted mucosal ecosystem: -Profound depletion of mucosal B cells and plasma cells -Expansion of highly cytotoxic CAR-T cells -Inflammatory remodeling across myeloid, stromal, and glial compartments -Telocyte-associated stromal niche dysfunction And importantly, interferon/JAK-STAT–associated reprogramming was detected across stromal, endothelial, and epithelial compartments. That observation provided a mechanistic rationale for targeting the pathway. In two patients, treatment with the selective JAK1 inhibitor upadacitinib was associated with clinical, endoscopic, and histologic improvement. The bigger story is that CAR-TEC may not simply represent “GI toxicity” from CAR-T. It may represent a multicellular failure of mucosal homeostasis arising from profound B-cell/plasma-cell depletion, persistent immune activation, and remodeling of the intestinal tissue environment. As B-cell–targeted therapies expand beyond oncology and into autoimmune disease, understanding what happens to the tissues that depend on these immune populations may become increasingly important. The next frontier of CAR-T safety may be understanding not only what happens to the tumor—but what happens to the immune ecosystems surrounding it. nature.com/articles/s41591-0… #CART #MultipleMyeloma #CellTherapy #Immunotherapy #CARTEC #Gastroenterology #TranslationalMedicine #CancerResearch

Excited to share a preprint of my main PhD work in @nickpolizzi_'s lab - introducing LUCI-tag, a new orthogonal self-labeling protein tag based on K-Ras(G12C) and its covalent inhibitors! biorxiv.org/content/10.64898… (1/16)

Blood proteomics of menopause map to brain aging and dementia risk nature.com/articles/s41591-0…

Australia has been hacked. 'And today, I spoke with the CEO of OpenAI, Sam Altman, to express Australia's extreme concern about this incident. And I also expressed my disappointment that it took the company way too long to inform the government what had occurred, and the nature of the way that that notification occurred as well was unacceptable.'

My almost-three year old has been walking around singing the “couldn’t be alone…couldn’t be alone.” from Burial’s Archangel. The experiment to create a new type of guy is going better than anyone could’ve hoped

Does your Claude model really need Claude Code…? 🤔 We evaluate 7 models on Claude Code, Codex, and Pi. Three surprising findings emerge: 1️⃣Harness choice has little effect on task success rate, but can significantly affect the cost 2️⃣A simple harness can be competitive 3️⃣The native harness isn’t always the best. Millions of people are using coding agents, but the impact of harness choice remains unclear. (1/n) More details in the thread. 🧵