On February 15, 2024 Lantern Pharma Inc. (NASDAQ: LTRN), a leader in AI-driven cancer drug discovery and development, reported an important milestone in its antibody-drug conjugate (ADC) program (Press release, Lantern Pharma, FEB 15, 2024, View Source [SID1234640162]). In collaboration with Bielefeld University, Lantern has generated a new class of highly specific and highly potent ADCs with a cryptophycin drug-payload.
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
This novel approach utilizes cysteine-engineered antibodies which allows for the development of uniform and homogenous ADCs with precise control of the drug to antibody ratio (DAR). The drug-payload, cryptophycin, has the potential to improve upon existing ADCs used in the clinical setting by: 1) improving the anti-tumor potency of the ADC molecule, and 2) overcoming drug resistance tumors can frequently develop to existing drug-payloads such as MMAE (Monomethyl auristatin E). The cryptophycin drug-payload and cryptophycin-ADC (CpADC) averaged an 80% cancer cell kill rate across the tested cancer cell lines and significantly outperformed MMAE.
In a broad range of preclinical studies, the cryptophycin-ADC (Cp-ADC) demonstrated promising picomolar level potency and anti-tumor activity in a wide range of solid tumors, including six cancer indications that are being further evaluated. These six indications include: breast, bladder, colorectal, gastric, pancreatic and ovarian cancer. Initial results (Figure 1) have also shown that in high Her2 expressing tumors, Cp-ADC with a DAR of 8 (Tras(C8)-Cp) and DAR of 4 (Tras(C4)-Cp) is more potent than an MMAE ADC with a DAR of 8. MMAE payloads are used in several commercially available anti-cancer ADCs, including Adcetris, Polivy and Enhertu. Additionally, the Cp-ADC with a lower DAR (Tras(C2)-Cp) provides an equivalent tumor kill-rate to that of an MMAE-ADC with a DAR of 8. In a moderate Her2 expressing cell line, the Cp-ADC with a DAR of 8 (Tras(C8)-Cp) was about 10 times more potent than a DAR 8 MMAE-ADC.
The newly developed Cp-ADC showed highly efficient anti-tumor activity in all six cancer cell lines with EC-50 values in the picomolar to single-digit nanomolar range. Additional studies are now being developed to further validate and expand these findings and to obtain a better understanding of the genomic and biomarker correlates of payload efficacy across these tumors.
Kishor Bhatia, Ph.D., Lantern’s Chief Scientific Officer commented, "Our strategic, data-driven approach of utilizing cryptophycin as a highly potent and novel payload alongside the prioritization of biologically novel and relevant targets with scalable and efficient drug conjugate formats will help expand the repertoire and diversity of ADC opportunities."
Lantern is also utilizing its AI platform, RADR to further refine and understand other cancer targets, with a focus on prioritizing targets that are expressed across multiple tumor types or subtypes and have few or no therapeutic ADC options. Given the promise of cryptophycin as a payload, Lantern is also focused on the development and testing of two other cryptophycin-ADC molecules. For these selected targets, Lantern is in advanced discussions with potential partners and collaborators with the goal of generating proof-of-concept data for these additional ADCs and potentially other novel drug conjugate formats. Lantern expects to provide additional details on these studies and collaborations in the coming quarters. These efforts aim to improve ADC development for specific patient populations and potentially guide more effective future clinical treatments with less cost and greater efficiency than historical ADC drug development.