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MD Anderson and Generate:Biomedicines enter co-development and commercialization agreement to accelerate novel protein therapeutics for oncology using generative AI

The University of Texas MD Anderson Cancer Center and Generate:Biomedicines today announced a strategic collaboration to jointly discover and co-develop protein therapeutics for up to five oncology targets in advanced cancers, including small-cell and non-small-cell lung cancer.

Under the co-development and commercialization agreement, MD Anderson and Generate:Biomedicines will each contribute toward creating optimized, potentially best-in-class therapeutics that can rapidly advance into proof-of-concept clinical trials. The agreement combines Generate:Biomedicines’ integrated machine-learning capabilities and experimental/wet lab capabilities – which are powered by The Generate Platform – with MD Anderson’s clinical research expertise and the translational research and drug development capabilities of the Translational Research to AdvanCe Therapeutics and Innovation in Oncology (TRACTION) platform.

“Together with Generate:Biomedicines, we aim to leverage rapid advancements in generative AI to develop new medicines that are purpose-built for those who do not benefit from existing treatments or who have drug-resistant cancers requiring new options,” said Timothy Heffernan, Ph.D., vice president of Oncology Research for TRACTION at MD Anderson. "By joining The Generate Platform with our integrated translational research and drug development approach, we hope to successfully scale drug discovery and development in a way that has eluded traditional trial-and-error methods.”

By tapping into the programmability and scalability of The Generate Platform, researchers within TRACTION and across the MD Anderson research enterprise will accelerate the pace of drug development and inform clinical translation. TRACTION is a core component of MD Anderson’s Therapeutics Discovery division that deploys a fully integrated translational biology engine to overcome traditional challenges in oncology drug discovery.

“Our collaboration with MD Anderson is an embodiment of innovative and cooperative research purposed to maximize the clinical impact of new therapeutics in oncology,” said Generate:Biomedicines’ Chief Medical Officer, Alex Snyder, M.D. “Together, we aim to deploy disruptive technology that will enable us to completely reimagine how we identify and pursue therapeutic targets, with the goal of creating new therapies for patients faster than ever before.”

Under the agreement terms, Generate:Biomedicines and MD Anderson will share research and development expenses as well as funds generated through commercialization of products that emerge from the collaboration. The organizations also anticipate that MD Anderson will serve as a site and recommend lead investigators for Phase I and II clinical trials of any jointly developed therapeutic product candidates.

Disclosure
MD Anderson has an institutional conflict of interest with Generate related to this research, and this relationship will be managed according to an MD Anderson Institutional Conflict of Interest Management and Monitoring Plan.

MD Anderson and Xilis announce strategic collaboration to advance novel technology and accelerate therapeutic development

The University of Texas MD Anderson Cancer Center and Xilis today announced a strategic collaboration to deploy Xilis’ proprietary MicroOrganoSphere™ (MOS) technology in support of preclinical research to accelerate the development of novel cancer therapies.

Under the agreement, the two organizations aim to advance drug development and discovery projects utilizing the MOS platform, which enables translational research on patient-derived micro tumors with new capabilities and at a scale not possible with current in vivo models. If successful, this platform may offer opportunities for third-party collaborations to guide the development of new drugs and cell therapies.

“Our research suggests the MOS platform has the potential to offer new capabilities and to improve the efficiency of developing innovative drugs and cell therapies over current xenograft and organoid models, which we hope will bring medicines to patients more quickly,” said Xiling Shen, Ph.D., chief executive officer and co-founder of Xilis. “We look forward to working with the MD Anderson team to discover and develop the next generation of cancer treatments, and we welcome further conversations with pharmaceutical firms for tripartite drug development opportunities.”

The MOS platform at MD Anderson will be run jointly by the Xilis and MD Anderson teams, and the collaboration will be led by three MD Anderson scientists: Timothy Heffernan, Ph.D., vice president of Oncology Research for MD Anderson’s Translational Research to AdvanCe Therapeutics and Innovation in ONcology (TRACTION) platform, Scott Kopetz, M.D., Ph.D., professor of Gastrointestinal Medical Oncology, and Katy Rezvani, M.D., Ph.D., professor of Stem Cell Transplantation & Cellular Therapy.

The MOS technology provides the first reliable platform to rapidly assess how a patient’s tumor responds to a wide variety of cancer drug modalities within 14 days of obtaining harvested tumor cell samples while also sustaining the native tumor microenvironment. This is essential for determining the full spectrum of therapeutic effects, including immuno-oncology, in the clinic.

The platform also is capable of accelerating the development of disease models, enabling new opportunities to further support discovery research, translational science and drug development efforts. The collaborators intend to explore how the MOS platform could be used to establish new patient-derived models underrepresented in the field, such as rare cancers and treatment-resistant disease.

“The ability to rapidly screen many drugs ex vivo and to build an expansive catalog of disease models addressing unmet needs opens new avenues to advance impactful medicines,” Heffernan said. “Our collaboration with Xilis will allow us to evaluate this exciting technology as a tool to improve the scale, speed and capabilities of our translational research efforts.”

The TRACTION platform, a core component of MD Anderson’s Therapeutics Discovery division, is designed to accelerate the development of innovative cancer therapies and to identify the right treatment for the right patients. MD Anderson’s natural killer (NK) cell therapy program, led by Rezvani, is advancing novel treatments for a variety of cancers using engineered cord blood-derived NK cells.

“Developing impactful cell therapies requires an accurate determination of which cells can produce the desired effect prior to introduction in patients,” Rezvani said. “In collaboration with the Xilis team, we aim to deploy the MOS platform to enable rapid screening and increase our chances of clinical success in our NK cell therapy program.”

MD Anderson Research Highlights for February 1, 2023

The University of Texas MD Anderson Cancer Center’s Research Highlights showcases the latest breakthroughs in cancer care, research and prevention. These advances are made possible through seamless collaboration between MD Anderson’s world-leading clinicians and scientists, bringing discoveries from the lab to the clinic and back.

Recent developments include results from a small-molecule inhibitor of oxidative phosphorylation, early antitumor response from a targeted therapy in patients with liposarcoma, the identification of epigenetic therapeutic targets in small cell lung cancer, a prognostic tool to help inform breast cancer therapy recommendations, a study of disparities in early mortality for adolescents and young adults with cancer, and a potential approach to improve treatment response in soft-tissue sarcomas.

Clinical trials of MD Anderson-developed therapy bring new insights to targeting oxidative phosphorylation
Certain tumors become dependent on the oxidative phosphorylation (OXPHOS) metabolic pathway for cellular energy production, making it an attractive target for new cancer therapies. However, clinical benefit with OXPHOS inhibitors has not yet been realized. Scientists in the Institute for Applied Cancer Science and the TRACTION platform, both part of MD Anderson’s Therapeutics Discovery division, developed the OXPHOS inhibitor IACS-10759, a small-molecule targeting the group of OXPHOS proteins known as Complex I. Timothy Yap, M.B.B.S., Ph.D., Naval Daver, M.D., Philip Jones, Ph.D., Joseph Marszalek, Ph.D., and colleagues evaluated IACS-10759 in two Phase I trials for advanced solid tumors and advanced acute myeloid leukemia. The treatment achieved transient target inhibition, but frequently was associated with neurotoxicity and elevated blood lactate levels. As a result, both trials were discontinued. The results reveal important insights for the field, providing guidance and caution for future development of OXPHOS inhibitors. Learn more in Nature Medicine.

MDM2 inhibitor milademetan shows early evidence of antitumor activity
The MDM2 protein is a negative regulator of the p53 tumor suppressor protein, and the MDM2 inhibitor milademetan aims to restore the p53’s antitumor activity. In a first-in-human Phase I trial led by David S. Hong, M.D., milademetan showed evidence of antitumor activity, especially in dedifferentiated liposarcoma. The primary objective in the study was to determine the recommended Phase II dose and schedule, which was found to be 260 mg once daily for three of 14 days. More continuous regimens were associated with on-target toxicities. In 107 patients, the overall disease control rate (DCR) was 45.8% and the median progression-free survival (PFS) was four months. In the subgroup with dedifferentiated liposarcomas, the DCR was 58.5% and median PFS was 7.2 months. The most common grade 3-4 drug-related adverse events were thrombocytopenia (29%), neutropenia (15%) and anemia (13.1%). Phase II and Phase III trials evaluating milademetan currently are underway. Learn more in the Journal of Clinical Oncology.

SET2,3 test added independent information to recurrence score for node-positive breast cancer
The 21-gene breast recurrence score (RS) is used to decide whether chemotherapy would provide additional benefit to hormone therapy alone for patients with lymph node-positive breast cancer. A different test (SET2,3 index) developed by Fraser Symmans, M.D., predicts the cancer’s sensitivity to endocrine therapy relative to baseline prognostic characteristics. Researchers from the National Clinical Trials Network’s Southwest Oncology Group (SWOG) tested whether the SET2,3 index added predictive or prognostic information to the RS using samples from the SWOG S8814 trial, which evaluated adjuvant anthracycline-based chemotherapy followed by tamoxifen hormone therapy for five years compared with tamoxifen alone. While SET2,3 index did not predict benefit from anthracycline-based chemotherapy, it had no correlation with RS and their combined results significantly improved prognostic assessment. Further work is needed to determine when and how multiple assays should be used in breast cancer treatment and to evaluate SET2,3 index with contemporary endocrine-based treatments. Read more in the Journal of Clinical Oncology.

Preclinical study identifies potential therapeutic targets in small cell lung cancer
Small cell lung cancer (SCLC) is highly malignant and has no currently approved targeted therapies. The CARM1 enzyme plays a role in promoting gene transcription, and its inhibition improves anti-tumor activity in various other cancers. However, its downstream targets are not well understood, and its therapeutic value has not been tested in SCLC. The NFIB transcription factor, which often is amplified in SCLC, is a substrate for CARM1. To characterize this relationship, researchers led by Guozhen Gao, Ph.D., Simone Hasumann, Ph.D., Pawel Mazur, Ph.D., and Mark Bedford, Ph.D., used in vivo SCLC models to show that CARM1 is a transcriptional coactivator for NFIB and affects gene expression through methylation at a single site. Losing NFIB methylation via CARM1 inhibition or NFIB mutation blocked tumor progression in these models. This study highlights NFIB amplification and CARM1 as drivers of rapid SCLC onset, meriting further investigation as therapeutic targets. Learn more in Nature Communications.

Disparities in early mortality persist for adolescent and young adults with cancer
While overall survival for adolescent and young adults (AYAs) with cancer has improved, with current five-year survival rates of more than 80%, a subset of patients remains at risk of dying shortly after their initial diagnosis, and certain sociodemographic factors have been associated with these disparities. To better understand these factors, researchers led by Michael Roth, M.D., used the Surveillance, Epidemiology, and End Results (SEER) database to analyze 268,501 AYAs diagnosed during a 16-year period. Results showed 3,854 AYAs died within two months of being diagnosed, and those with acute leukemia, liver, bile duct, pancreatic and lung cancer were at highest risk for early death. Hispanic and Black AYAs also were at the highest risk for early death, while other associated factors included lower socioeconomic status, limited or no health insurance, and presentation with higher stage disease at initial diagnosis. More research is needed to identify the underlying causes and reduce disparities in early survival for AYAs diagnosed with cancer. Learn more in the Journal of the National Cancer Institute.

Sequential targeting of cell cycle to prime retinoblastoma and induce DNA damage could improve anti-tumor response in sarcomas
Soft tissue sarcomas (STS) are rare cancers that form in tissues surrounding body organs, and there currently is a lack of effective treatment options. Reactivating the retinoblastoma (Rb) pathway with CDK4/6 inhibitors has been successful in other cancers, but these inhibitors have not shown much efficacy in STS as monotherapy or when combined with chemotherapy. Chemotherapy agents work by targeting a later stage of the cell cycle, making them inefficient if concurrent CDK4/6 inhibitors have already arrested cell cycle progression. Therefore, researchers led by Khandan Keyomarsi, Ph.D., evaluated a novel two-step sequential treatment approach. They first administered the CDK4/6 inhibitor abemaciclib to prime Rb-positive tumor cells, then removed the drug and allowed a recovery period, permitting the cell cycle to progress before giving chemotherapy. This sequential process, which can be non-invasively monitored in real time, effectively killed tumors in in vitro and in vivo, highlighting its therapeutic and clinical translation potential. Learn more in Cancer Research.

Recent awards and honors
Four MD Anderson researchers were elected members of the American Society for Clinical Investigation:

Courtney DiNardo, M.D., associate professor of Leukemia
Anirban Maitra, M.B.B.S., professor of Pathology and Translational Molecular Pathology
Katy Rezvani, M.D., Ph.D., professor of Stem Cell Transplantation & Cellular Therapy
Hussein Tawbi, M.D., Ph.D., professor of Melanoma Medical Oncology

In case you missed it
Read below to catch up on recent MD Anderson press releases.

MD Anderson and Exscientia launch strategic collaboration to leverage AI in developing novel oncology treatments

The University of Texas MD Anderson Cancer Center and Exscientia plc today announced a strategic collaboration to align the drug discovery and development expertise of MD Anderson with the patient-centric artificial intelligence (AI) capabilities of Exscientia in order to advance novel small-molecule oncology therapies.

The research collaboration will utilize Exscientia’s precision medicine platform to identify novel anti-cancer, cell-intrinsic small-molecule compounds based on jointly identified therapeutic targets. Promising candidates will advance for further development with the team at MD Anderson’s Therapeutics Discovery division. The collaborators anticipate that successful target discovery programs may be advanced into proof-of-concept clinical trials at MD Anderson.

“We are driven to develop the next generation of oncology treatments that can offer meaningful benefits and improve the lives of our patients,” said Philip Jones, Ph.D., vice president of Therapeutics Discovery and head of the Institute for Applied Cancer Science (IACS) at MD Anderson. “This collaboration is built upon Exscientia’s AI-driven precision medicine platform, the strength of MD Anderson’s drug discovery and development engine, and the expertise of our clinical research teams. Our ultimate goal is to decrease the time we spend in drug development and accelerate novel targeted therapies into the clinic.”

Exscientia will collaborate with the team at IACS, a drug discovery engine focused on developing novel small-molecule therapeutics. IACS is a core component of MD Anderson’s Therapeutics Discovery division, an integrated team of researchers, physicians and drug development experts working to advance impactful new therapies.

“We are tremendously proud to work alongside MD Anderson to harness our AI-driven platform toward the discovery of next-generation cancer treatments. Artificial intelligence has opened up new possibilities in cancer research, enabling us to use deep learning multi-omics within our precision medicine platform to test potential drug candidates in Exscientia’s patient tissue models,” said Andrew Hopkins, D.Phil., founder and chief executive officer of Exscientia. “Further, our platform holds the potential to stratify patients even in the early discovery stage, allowing us to efficiently design drug candidates that are most likely to be impactful for people with cancer.”

Under the agreement terms, Exscientia and MD Anderson will jointly contribute to and support each program designated to move forward.

Disclosure

MD Anderson has an institutional conflict of interest with Exscientia, and this relationship will be managed according to an MD Anderson Institutional Conflict of Interest Management and Monitoring Plan.