Oregon Therapeutics and Lantern Pharma Collaborate on AI-Optimized Drug Development for XCE853
Monday, May 13, 2024
Oregon Therapeutics and Lantern Pharma Launch Strategic Artificial Intelligence Collaboration to Optimize Development of XCE853, a Potent Cancer Metabolism Inhibitor and First-in-Class Drug Candidate
Lantern Pharma Inc. (NASDAQ: LTRN), a leading oncology drug discovery and development company powered by artificial intelligence (AI), today announced an AI-enabled strategic collaboration with the biotechnology company company Oregon Therapeutics in order to optimize the development of its drug candidate XCE853, the first protein disulfide isomerase (PDI) inhibitor (1) , in new and targeted indications against cancer. Lantern will use its proprietary RADR ® AI platform to discover biomarkers and genetic signatures associated with XCE853 efficacy in solid tumors. This work should make it possible to identify biomarkers that can be used to stratify the tumors most sensitive to XCE853 and guide clinical development and patient selection. Oregon Therapeutics is developing XCE853 in several oncology indications, including ovarian and pancreatic cancers, certain hematologic cancers, and several pediatric cancers, including neuro-oncology.
PDIs are promising targets for cancer treatment, which have recently attracted strong clinical interest 2 , due to their potential in cancers with poor prognosis such as breast cancer 3 or ovarian cancer. Several clinical studies have demonstrated that increased PDI expression is associated with increased mortality in cancers such as hepatocellular carcinoma (4) , as well as breast and ovarian cancers (5) . PDIs are chaperone proteins that play a central role in cancer cell metabolism. PDI inhibitors can lead to cancer cell death through accumulation of altered proteins and dysregulation of cellular stress responses. The combination of these effects is known as proteotoxicity , a unique and promising therapeutic strategy that could be particularly effective in targeting cancers resistant to certain reference oncology drugs.
In the United States, nearly 612,000 people (6) will die from cancer in 2024 and resistance to anticancer drugs will be involved in 90% of these deaths (7). To date, no PDI inhibitor has reached the clinical stage due to the complexity associated with selecting and mapping molecules that will more precisely target the appropriate PDI enzymes. There are over 20 PDI enzymes, each playing a slightly different and often biologically redundant role. Oregon Therapeutics' lead drug candidate - XCE853 - is known to target IDPs with a specific role in oncology. Lantern Pharma and Oregon Therapeutics believe that computational tools – including fundamental models, machine learning and large-scale molecular analysis – can provide an ideal, simplified path to analyzing and understanding the complexity of this data, making RADR ® the perfect platform that can deliver key information on the role that the drug candidate XCE853 can play in the effective treatment of cancer. (8, 9)
“To date, our first metabolic inhibitor, XCE853, has demonstrated robust preclinical efficacy in in-vitro and in-vivo models of numerous cancer types,” said Marc-Henry PITTY, President of Oregon Therapeutics. “Lantern's RADR ® AI platform will leverage our in-vitro and in-vivo data to advance the development of biomarkers that can help in the design of clinical trials, as well as the development of combination therapies with other drugs for the treatment of cancer. Our team looks forward to being able to efficiently select ideal development options and de-risk future clinical development decisions. » Oregon Therapeutics has already performed preclinical studies demonstrating that in addition to ovarian and pancreatic cancers, XCE853 may also be particularly active in kidney, prostate, lung, breast, spherical, ENT, as well as in leukemia.
Sandrine Courtès , project manager at Oregon, having developed the collaboration with Lantern Pharma, declares: “ PDI inhibitors have great potential, because this molecular target is highly expressed in several types of cancer, promotes tumor growth and is significantly correlated with clinical results. »
This collaboration will mainly focus on the integration and analysis of molecular, genetic and transcriptomic data relating to XCE853. The analysis will be powered by RADR ® and its growing library of more than 60 billion data points from various types of biological measurements and oncology experiments, as well as more than 200 problem-focused ML algorithms that are – in reality - at the heart of the challenges linked to the development of anticancer drugs. The initial objectives of the collaboration are:
1) discover biomarkers and genetic signatures associated with the efficacy of XCE853, in order to guide the stratification and selection of patients for future clinical trials,
2) identify mechanisms of treatment resistance and tumor response to XCE853 and strategies to overcome these resistance mechanisms, and
3) extend the use of XCE853 to other therapeutic indications in oncology for XCE853.
“Drug development teams have faced significant data and modeling challenges in dealing with the complexities associated with PDI inhibitors, given the challenges of creating relevant models, accumulating and deciphering data,” says Panna Sharma, Chief Executive Officer, Lantern Pharma. “Our AI platform, RADR ® , can increase confidence, knowledge and comfort levels in developing development pathways based on preclinical data by modeling highly complex scenarios at a scale that is not yet possible. only recently become possible. This is an ideal approach for Oregon Therapeutics, which has completed a series of highly focused in vivo and in vitro experiments and is poised to make incredibly important, patient-centered decisions regarding the molecule's clinical future. This is where RADR ® can play an essential and decisive role in meeting market needs. »
Under the terms of the collaboration, Lantern Pharma receives an equal share of intellectual property and drug development rights for newly discovered biomarkers, new indications and/or new pharmacological use strategies for XCE853 and related analogues. Oregon Therapeutics will receive revenues related to the granting of a license to Lantern Pharma to exploit its patents. Finally, Lantern Pharma and Oregon Therapeutics will share additional financial revenues resulting from licensing the collaboration's intellectual property to a third party. No further financial details regarding the collaboration have been disclosed.
References
- Prevost GP et al. Abstract 3760: XCE853 is a promising protein disulfide isomerase (PDI) inhibitor exhibiting a strong inhibitory activity in preclinical tumor models. Cancer Res. (2016) 76 (14_Supplement): 3760. https://doi.org/10.1158/1538-7445.AM2016-3760
- Shili Xu, Saranya Sankar, Nouri Neamati, Protein disulfide isomerase: a promising target for cancer therapy, Drug Discovery Today, Volume 19, Issue 3, 2014, Pages 222-240, ISSN 1359-6446, https://doi.org/ 10.1016/j.drudis.2013.10.017 . ( https://www.sciencedirect.com/science/article/pii/S135964461300384X )
- Powell LE, Foster PA. Protein disulfide isomerase inhibition as a potential cancer therapeutic strategy. Cancer Med. 2021 Apr;10(8):2812-2825. doi:10.1002/cam4.3836. Epub 2021 Mar 20. PMID: 33742523; PMCID: PMC8026947.
- Yu, Won et al. 2014, Korean J Intern Med 29(5): 580-587), brain tumors (Zou et al. 2018, Oncol Rep. Feb;39(2):501-510.)
- Samanta et al. 2017, Oncotarget. Nov 28; 8(61): 103543–103556
- Siegel RL, Giaquinto AN, and Jemal A. Cancer statistics 2024. CA: A Cancer Journal for Clinicians. (Jan/Feb 2024) 74 (1): 12-49. https://doi.org/10.3322/caac.21820
- Longley DB and Johnston PG Molecular mechanisms of drug resistance. The Journal of Pathology. (Jan 2005) 205 (2): 275-292. https://doi.org/10.1002/path.1706
- Rutkevich LA, Cohen-Doyle MF, Brockmeier U., Williams DB (2010). Molecular Biology of the Cell. 21:3093–105. https://doi.org/10.1091/mbc.e10-04-0356
- Watanabe MW, Laurindo, FRM, Fernandes, DC Frontiers in Chemistry. (2014). Methods of measuring protein disulfide isomerase activity: a critical overview. 2, 73. https://www.frontiersin.org/articles/10.3389/fchem.2014.00073/full
About RADR ®
RADR ® is Lantern Pharma's proprietary integrated AI platform for large-scale analysis of biomarkers and drug-tumor interaction data, powered by machine learning. It is used to provide mechanistic insights into drug-tumor interactions, predict the potential response of cancer types and subtypes to existing drugs and drug candidates, and discover patient groups likely to respond to potential therapies. developed by Lantern Pharma and its collaborators.
RADR ® uses a comprehensive approach to apply its library of algorithms to statistical, correlative, and inferential problems of drug interactions with tumors. This allows the platform to quickly analyze very large amounts of complex data and predict how patients and tumors will respond to therapeutic combinations. RADR ® also evolves as new data sets are added, helping to improve and refine the knowledge generated by the algorithms.
RADR's highly scalable machine learning methods are designed to guide drug development and bring new biological insights, while having the potential to increase response rates and improve clinical trial outcomes. The robustness and growing volume of data that powers RADR ® is expected to continue to improve machine learning results, accelerate the automation of other functions, and facilitate oncology drug development for Lantern and its partners, in the ultimate goal of helping cancer patients.
About LANTERN PHARMA
Lantern Pharma (NASDAQ: LTRN) is an AI company transforming the cost, pace and timeline of oncology drug discovery and development. Our proprietary RADR ® AI and machine learning platform leverages more than 60 billion oncology-focused data points and a library of more than 200 advanced machine learning algorithms to help solve real-world problems in drug development. oncology drugs, which are worth billions of dollars. By harnessing the power of AI, with the help of world-renowned scientific advice, and the quality of its collaborators, we have accelerated the development of our growing portfolio of therapies spanning multiple cancer indications, including solid tumors and blood cancers, as well as an antibody-drug conjugate (ADC) program. On average, our newly developed drug programs have moved from early AI discoveries to first human clinical trials in 2 to 3 years, at an approximate cost of $1.0 to $2.5 million per program.
Lantern's principal development programs include a Phase 2 clinical program and several Phase 1 clinical trials. We have also established a wholly-owned subsidiary, Starlight Therapeutics, to focus exclusively on the clinical development of our promising cancer therapies. of the CNS and brain, many of which do not have effective treatment options. Our pipeline of innovative AI-based product candidates is estimated to have a combined annual market potential of more than US$15 billion and could deliver life-changing therapies to hundreds of thousands of cancer patients around the world .
More information on :
- Website: www.lanternpharma.com
- LinkedIn: https://www.linkedin.com/company/lanternpharma/
- X: @lanternpharma
About the XCE853
XCE853 is a proprietary drug candidate from Oregon Therapeutics, developed at an advanced preclinical stage for the treatment of multiple cancers resistant to reference oncology drugs. XCE853 is a synthetic small molecule that exhibits excellent inhibitory activity on major human PDIs playing key roles in cancer. XCE853 exhibits cytotoxic activity in the nanomolar range on a wide panel of cancer cells (more than 80 models) and is particularly more potent on a panel of models resistant to multiple drugs. XCE853 demonstrated promising ex-vivo activity in patient samples. It also has excellent oral bioavailability in mice and was able to completely and irreversibly block the growth of several human cancers in in vivo xenograft models. Preliminary toxicity in rats and mice showed an acceptable safety profile. This comprehensive package of preclinical, transcriptomic, and mechanism-of-action data will be complemented by insights from Lantern's artificial intelligence platform, RADR ® , to position the XCE853 drug candidate on an optimized and focused clinical development pathway. on the needs of patients.
About OREGON THERAPEUTICS
Oregon Therapeutics is a French preclinical biotechnology company developing PDI inhibitors from innovative drug discovery programs. Oregon developed XCE853 to regulatory preclinical stage and demonstrated the breakthrough potential of XCE853 as first-in-class and best-in-class in oncology. The main objective of Oregon Therapeutics is to bring XCE853 to the clinical phase for the treatment of cancers in collaboration with Lantern Pharma. Based on the scientific rationale aimed at exploiting the metabolic vulnerability of certain cancers, the two priority indications are ovarian cancer and advanced pancreatic cancer. Other potential indications include liver cancer, prostate cancer, ENT cancers and several orphan cancers.
More information on :
- Website: www.oregon-therapeutics.com
- Contact: Dr Marc-Henry PITTY, CEO: oregontherapeutics@gmail.com
Forward-looking statements:
This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. These forward-looking statements include, among other things, statements regarding the following: future events or future financial performance of Lantern; the potential benefits of Lantern's RADR ® platform in identifying drug candidates and patient populations likely to respond to a drug candidate; Lantern's strategic plans to advance the development of its drug candidates and its antibody-drug conjugate (ADC) development program; estimates regarding the development schedule of Lantern's drug candidates and the ADC development program; expectations and estimates regarding the timing of clinical trials and patient recruitment; the research and development efforts of Lantern's internal drug discovery programs and use of the RADR ® platformto harmonize the drug development process; Lantern's intention to leverage artificial intelligence, machine learning and genomic data to streamline and transform the pace, risk and cost of oncology drug discovery and development and to identify patient populations likely to respond to a drug candidate; estimates regarding patient populations, potential markets and potential market sizes; sales estimates for Lantern's drug candidates and its plans to discover and develop drug candidates and to maximize their commercial potential by advancing these drug candidates themselves or in collaboration with others. Any statement that is not a statement of historical fact (including, without limitation, statements that use words such as "anticipate", "believe", "consider", "could", "estimate") , “expect”, “intend”, “seek”, “may”, “could”, “plan”, “potential”, “predict”, “project”, “target”, “ model”, “objective”, “goal”, “future”, “should”, “will”, or the negative of these terms or other similar expressions, should be considered forward-looking statements. number of important factors that could cause Lantern's actual results to differ materially from those indicated in the forward-looking statements, such as (i) the risk that the research of Lantern and its collaborators will not be successful, (ii) ) the risk that promising observations in preclinical studies do not guarantee that subsequent studies and development will be successful, (iii) the risk that Lantern will not be successful in licensing potential candidates or entering into partnerships and potential collaborations, (iv) the risk that none of Lantern's product candidates have received marketing authorization from the FDA, and that Lantern is unable to initiate, conduct or conclude successfully complete clinical trials for its product candidates or obtain marketing authorization for the latter, (v) the risk that no pharmaceutical product based on Lantern's proprietary RADR ® AI platform has received marketing authorization from the FDA or been incorporated into a commercial product, and (vi) the other factors set forth in the Risk Factors section of Lantern's Annual Report on Form 10-K for fiscal year ended December 31, 2023, filed with the Securities and Exchange Commission on March 18, 2024. You can access Lantern's Annual Report on Form 10-K for the fiscal year ended December 31, 2023 under the Filings tab at SEC from our website atwww.lanternpharma.com or on the SEC's website at www.sec.gov . Given these risks and uncertainties, Lantern can give no assurance that the forward-looking statements contained in this press release will prove to be accurate, or that any other results or events projected or contemplated by the forward-looking statements contained in this press release will actually occur, and Lantern cautions investors not to place undue reliance on these statements. All forward-looking statements by Lantern in this press release represent Lantern's judgment as of the date hereof and, unless otherwise required by law, Lantern disclaims any obligation to update any forward-looking statements to conform them to actual results or changes. in his expectations.
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Contacts
Investor Relations at Lantern Pharma
ir@lanternpharma.com
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