DR3

— XmAb942 on track for first subject dosing in Phase 1 healthy volunteer study in Q4 2024 — PASADENA, CA, USA I October 10, 2024 I Xencor, Inc. (NASDAQ: XNCR), a clinical-stage biopharmaceutical company developing engineered antibodies for the treatment of cancer and other serious diseases, today announced that preclinical data on XmAb942 were published in a poster to be presented during United European Gastroenterology (UEG) Week on Tuesday, October 15 in Vienna, Austria. XmAb942 is a high-potency, extended half-life, investigational anti-TL1A antibody to be developed for patients with inflammatory bowel diseases, such as ulcerative colitis (UC) and Crohn’s disease (CD). The first generation of anti-TL1A antibodies, designed to block the interaction between the DR3 receptor and its ligand TL1A, have reduced disease activity in patients with UC and CD in multiple clinical studies. Xencor anticipates dosing the first subject in a first-in-human study of XmAb942 in healthy volunteers during the fourth quarter of 2024 and expects to present initial data from the single-ascending dose portion of the study in the first half of 2025. “We are aiming for XmAb942 to be the potential best-in-class next-generation anti-TL1A antibody, providing leading potency and less frequent dosing relative to the first generation TL1A-targeted antibodies, which have validated TL1A as an important inflammatory axis,” said John Desjarlais, Ph.D., executive vice president and chief scientific officer at Xencor. “Our preclinical data suggest that in vitro potency of XmAb942 is comparable or superior to first-generation anti-TL1A antibodies. XmAb942 also demonstrates superior pharmacokinetics with a half-life of 23 days in non-human primates, which we believe supports a potential eight- to twelve-week dosing regimen in humans and could improve convenience and potentially compliance within the TL1A class.” Xencor’s poster, titled “Discovery and Characterization of a Novel High-Affinity Anti-TL1A Monoclonal Antibody with Extended Half-life for the Treatment of Inflammatory Bowel Disease,” will be archived under the “Publications” and the “Events & Presentations” pages of the Company’s website located at www.xencor.com . About Xencor Xencor is a clinical-stage biopharmaceutical company developing engineered antibodies for the treatment of patients with cancer and other serious diseases. More than 20 candidates engineered with Xencor’s XmAb® technology are in clinical development, and multiple XmAb medicines are marketed by partners. Xencor’s XmAb engineering technology enables small changes to a protein’s structure that result in new mechanisms of therapeutic action. For more information, please visit www.xencor.com . SOURCE: Xencor

– Interim clinical data for SL-172154 in combination with azacitidine in TP53 mutant (TP53m) acute myeloid leukemia (AML) and higher-risk myelodysplastic syndromes (HR-MDS) showed only modest improvement in median overall survival compared to azacitidine monotherapy benchmarks; further development of SL-172154 discontinued – – Prioritization to focus on SL-325, a first-in-class antagonist antibody to DR3, the receptor for TL1A, intended for clinical development in inflammatory bowel disease (IBD); IND filing expected in Q3 2025 – – SL-172154 associated restructuring expected to extend cash runway into 2027 – AUSTIN, TX and DURHAM, NC, USA I October 01, 2024 I Shattuck Labs, Inc. (Shattuck) (Nasdaq: STTK), a biotechnology company pioneering the development of novel therapeutics targeting tumor necrosis factor (TNF) superfamily receptors for the treatment of patients with cancer and chronic immune-related diseases, today announced a strategic pipeline prioritization to include the discontinuation of its clinical program, SL-172154. The Company will turn its focus to SL-325, its DR3 antagonist antibody, and plans initial clinical development in patients with IBD, where TL1A/DR3 blocking antibodies have demonstrated compelling monotherapy efficacy. “We are disappointed that the promising complete remission rates we previously shared from our Phase 1 clinical trial did not translate to clinically meaningful improvements in median overall survival for TP53m AML and HR-MDS patients treated with SL-172154 in combination with azacitidine. We thank our clinical team and investigators for conducting an excellent clinical study, yet we must accept this result as it stands and move on to other opportunities with a higher probability of success,” said Taylor Schreiber, M.D., Ph.D., Chief Executive Officer of Shattuck. Dr. Schreiber continued, “We are announcing a strategic shift to focus on SL-325, a DR3 antagonist antibody designed to achieve a more complete blockade of the clinically validated TL1A/DR3 signaling pathway. We believe SL-325 could be a first-in-class DR3 receptor blocking antibody, and that this approach will prove more potent than blocking TL1A, for many of the same reasons that blocking PD-1 has proven more potent than blocking PD-L1. This strategic shift in our clinical development plans and subsequent realignment of our organization with an approximate 40% reduction in workforce will allow us to use our resources most efficiently to position Shattuck for long-term success. I would like to express my gratitude to the patients who participated in our clinical trials to date as well as to the Shattuck team members who were impacted by this realignment.” Top-line Phase 1B SL-172154 Clinical Trial Results HR-MDS TP53m AML Corporate Updates Financial Guidance Update As of June 30, 2024, cash and cash equivalents and investments were $105.3 million. Shattuck has implemented a restructuring plan to prioritize the development of the Company’s DR3 program. The plan is intended to optimize the Company’s cost structure by aligning the size and structure of its workforce with the Company’s current goals and strategy, following the discontinuation of SL-172154. Approximately 40% of Shattuck’s workforce will be impacted by the changes. The Company expects to complete the reduction in force in the fourth quarter of 2024. Given the changes to Shattuck’s operations and cost structure, the Company believes its cash and cash equivalents and investments will be sufficient to fund its planned operations into 2027, beyond results from its planned Phase 1 clinical trial of SL-325. This cash runway guidance is based on the Company’s current operational plans and excludes any additional capital that may be received, proceeds from potential business development transactions, and/or additional costs associated with additional development activities that may be undertaken. Shattuck Labs Investor Call and Webcast Shattuck will host a conference call and webcast at 8:00 a.m. ET on Tuesday, October 1, 2024, to discuss clinical data from SL-172154 and outline a strategic pipeline prioritization to focus on SL-325, a first-in-class DR3 antagonist targeting the TL1A/DR3 signaling pathway. Participants are invited to listen by dialing (800) 715-9871 (domestic) or +1 (646) 307-1963 (international) five minutes prior to the start of the call and providing the passcode 6989140. A live webcast presentation will be available here or on the company’s website at www.ShattuckLabs.com under Events & Presentations . A replay of the webcast will be archived on the company’s website following the presentation. About Shattuck Labs, Inc. Shattuck Labs, Inc. (Nasdaq: STTK) is a biotechnology company specializing in the development of potential treatments for autoimmune/inflammatory diseases and cancer. Shattuck is developing a potentially first-in-class antibody for the treatment of IBD and other inflammatory autoimmune diseases. Shattuck’s expertise in protein engineering and the development of novel TNF receptor agonist and antagonist therapeutics come together in its lead program, SL-325, a first-in-class DR3 antagonist antibody designed to achieve a more complete blockade of the clinically validated TL1A/DR3 pathway. Shattuck has offices in both Austin, Texas and Durham, North Carolina. For more information, please visit: www.ShattuckLabs.com . SOURCE: Shattuck Labs

Following the restructuring news, Shattuck’s stock was down by 44.99% at market close on 1 October, compared to market close on the previous day. Shutterstock: paper cut design / Shutterstock. Shattuck Labs has dropped by nearly 45% after it announced plans to reduce its headcount and discontinue its lead cancer therapy programme, SL-172154. The restructuring decision was made after interim data from a Phase Ib trial (NCT05275439) showed a lack of a definitive overall survival (OS) benefit in patients receiving SL-172154. The company added that the ‘modest’ improvements in the OS seen in Phase I would likely erode in larger late-stage studies. Following the announcement, Shattuck’s stock was down by 44.99% at market close on 1 October, compared to market close on the previous day. The company’s market cap currently stands at $81.6m. SL-172154 is a cluster of differentiation 47 (CD47) inhibitors, which were investigated as a treatment for myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML). In February, Shattuck licensed out multiple potential drug candidates, including SL-172154, to Ono Pharmaceuticals in a deal worth more than $227m. As part of the restructuring, the companies have mutually terminated the agreement and Shattuck is “no longer required to satisfy any remaining performance obligations and will not receive any future research activity reimbursements or upfront, milestone, or royalty payments from Ono”. See Also: ImmunoPrecise and Biotheus partner on bispecific antibodies to treat cancer Novaliq and Laboratoires Théa announce EC approval for dry eye disease therapy The cost-saving measures also cull 40% of the workforce by the end of the year and will cost between $1.5m and $1.75m. Shattuck reported cash reserves of $105.3m as of 30 June, as per the latest SEC filing by the company. The company plans to funnel its remaining resources into developing its antibody therapy, SL-325. The DR3 antagonist acts by modulating adaptive immunity, as DR3 is expressed on the cell surface of various immune cells. Shattuck is developing SL-325 as a treatment for inflammatory autoimmune diseases, including inflammatory bowel disease (IBD). The company plans to file an investigational new drug application (IND) for SL-325 in Q3 2025. Shattuck noted that it has sufficient funds to finance beyond its planned Phase I clinical trial of SL-325 and into 2027. Following the recent round of lay-offs, Shattuck joins the list of pharmaceutical companies, including Atreca , Candel Therapeutics , Cidara Therapeutics , Kinnate Bio , and NexImmune , which have cut their workforces to reallocate funds into their clinical development pipelines in the last few months.