[Edaily Reporter NA EUN-KYUNG ] #Orum Therapeutics, Inc., which halted development of a blood cancer drug candidate after selling it to BMS, is seeking a breakthrough through in-house clinical trials of a follow-up drug and the development of a new payload. The company plans to validate the potential of its existing GSPT1 degrader in the ORM-1153 clinical trial while expanding its development scope to include solid tumors and autoimmune diseases with drugs that degrade other proteins.

Lee Seung-ju, CEO of Orum Therapeutics, Inc., spoke with E-Daily following the “Innovative New Drug Salon Sinchon” event held at Yonsei University in Seodaemun-gu, Seoul, on the 21st. “Our researchers are working diligently on a new payload—the next platform for GSPT1—in the fields of oncology and autoimmune diseases,” he said. “We hope to show results in that area.”

Divers

ifying Degradation Targets… Also Reviewing External Technologies

Orum Therapeutics, Inc. develops antibody-drug conjugates (DACs) that attach protein degraders to antibodies. The mechanism involves the antibody delivering a drug to specific cells, where the payload then eliminates proteins involved in cell survival or disease.

ORM-5029 and ORM-6151, whose development has been halted, as well as ORM-1153, which is currently in clinical trials, all use “SMol006,” an in-house developed GSPT1 degrader, as their payload. GSPT1 degradation has been studied as an anticancer mechanism since the 2010s. CC-90009, developed by the U.S. biopharmaceutical company Celgene, is a prime example. While it has the potential to disrupt protein synthesis in cancer cells and even attack leukemia stem cells, side effects such as hypocalcemia and hypotension were observed in early clinical trials. Orum Therapeutics, Inc. aims to ensure both efficacy and safety by using antibodies to selectively deliver the drug to target cells.

Research into new payloads involves expanding the range of proteins that can be degraded. While continuing clinical validation of candidates utilizing the existing GSPT1 mechanism, the company is also exploring the potential of DACs for other cancer types and diseases where different mechanisms may be more suitable.

During a conference call on the 23rd of last month, CEO Lee explained, “This is a payload platform that degrades proteins other than GSPT1,” adding, “We have confirmed its efficacy in various solid tumors, including colorectal cancer, triple-negative breast cancer, ovarian cancer, and gastric cancer.” He continued, “Since we have confirmed its effectiveness with various antibodies and cancer models in mouse experiments, we plan to further accelerate research on new payloads.”

These are preclinical results; therapeutic efficacy in humans has not yet been confirmed. The company is also researching an approach to deliver degraders to specific cells in autoimmune and inflammatory diseases, but has not disclosed specific targets or candidate compounds.

As of the end of June, the company’s financial resources consisted of approximately 250 billion won in cash and short-term financial instruments. CEO Lee stated, “We will continue to advance the ORM-1153 clinical trial and research new payloads,” adding that the acquisition of external technologies is also under consideration. He cited “new antibodies or new payloads” as potential Daesangs for acquisition. However, he did not disclose specific Daesangs or the scale of investment.

ORM-1153 with a Modified Antibody: To Be Validated in Patients

The immediate test case is ORM-1153, for which the company announced the first patient dosing on the 14th. Since development of the two previous candidates—which used the same GSPT1 degrader—was halted, the company must verify what benefits the differences in the antibody and delivery method offer to patients.

The early-stage breast cancer candidate ORM-5029 utilized pertuzumab, a HER2-targeting antibody that is the active ingredient in “Perjeta,” which was approved in the U.S. in 2012. However, development was halted after a suspected serious adverse drug reaction related to liver failure occurred during a clinical trial using a new conjugate.

Subsequently, ORM-6151 utilized the antigen-binding site of gemtuzumab, a CD33-targeting antibody used in the ADC “Mylotag.” The company modified the antibody structure to reduce unnecessary binding to immune cells and also changed the linker connecting the antibody to the payload. During a conference call, CEO Lee explained this as a “design improvement to address the liver (toxicity) issue.”

ORM-1153 retains the payload and linker from ORM-6151 but switches the target from CD33 to CD123 and incorporates an in-house developed antibody. CEO Lee stated, “Starting with ORM-1153, we used a highly efficient antibody developed in-house,” adding, “Even when all other factors remained the same and only the antibody was changed, a difference in efficacy was observed.” However, these are preclinical results, and it has not yet been confirmed whether sufficient efficacy and safety have been established in humans.

The company did not provide specific details regarding the reasons for halting development of ORM-6151 or the status of discussions with BMS to verify clinical data. During a previous conference call, Chief Medical Officer (CMO) Olaf Christensen replied, “Due to confidentiality obligations, we cannot disclose the specific data we have.”

However, it is reported that ORM reviewed some information received from BMS and supplemented the information that ORM-1153 clinical trial participants must be informed of and consent to prior to dosing. The specific details of the added information were not disclosed. The company decided to maintain the trial protocol, judging that the existing safety monitoring system could address any major risks that could be anticipated.

The Phase 1 clinical trial will enroll approximately 42 participants to determine the optimal biological dose and assess safety and tolerability, as well as evaluate initial antileukemic effects. The company expects to gauge the drug’s development potential based on preliminary data by the end of 2027.

CEO Lee emphasized, “We administered the first dose to a patient at an extremely rapid pace following IND approval,” adding, “Professor Mighty of the MD Anderson Cancer Center, who serves as the principal investigator for the clinical trial, also has high hopes for ORM-1153 and is actively leading the trial.”

Regarding his recent purchase of 10,000 shares of the company’s stock on the open market, he explained, “Since the company holds a significant amount of cash, this was intended to demonstrate my commitment to the company,” adding, “I also took shareholders’ opinions into consideration.”