GI-102 Monotherapy Shows Strong Results in ESMO 2024 Interview

The 2024 ESMO Annual Congress, held from September 13th to 17th in Barcelona, Spain, showcased key advancements in cancer treatments. GI Innovation, focused on next-generation immuno-oncology therapies, shared their experience at the event and discussed their evolving pipeline.

GI Innovation is known for developing protein-based drugs through their GI-SMART platform, targeting immuno-oncology, allergies, and non-alcoholic steatohepatitis (NASH). Their pipeline includes several drug candidates in immuno-oncology, including GI-101, GI-102, GI-108, and GI-10N.

"Last year’s ESMO centered around competition in EGFR-mutant non-small cell lung cancer with presentations like the MARIPOSA trials. This year, the focus has shifted towards immuno-oncology and antibody-drug conjugates (ADCs), with over 100 ADC substances showcased.

We also saw new modalities like targeted protein degradation (TPD) and personalized treatments. Notably, in the 'Presidential Session,' AI-driven image analysis took the stage for the first time, offering a glimpse into the future of cancer treatment.

Significant long-term survival data for immuno-oncology drugs like Opdivo and Keytruda in melanoma were released, showing remarkable survival benefits even after a decade. Immunotherapy's continued success is promising, and new combinations and approaches for resistant patients are emerging."

"At ESMO, we focused on meetings with global pharmaceutical companies about our CD80-IL2v dual fusion protein 'GI-102.' We also held discussions with key opinion leaders (KOLs) on the accelerated approval path for this drug. GI-102 addresses immune cell depletion, a challenge in patients resistant to immunotherapy.

GI Innovation is currently working on out-licensing GI-102 globally, while also pursuing accelerated approval for certain indications. The primary target is immunotherapy-resistant melanoma, where the drug has shown the most promising results.

In this regard, we had in-depth discussions with Professor Georgina Long from the University of Sydney, a leading authority in melanoma research, and Professor Hussein A. Tawbi from MD Anderson Cancer Center, the world’s top cancer treatment center, about the development strategy for GI-102.

Professor Georgina Long has been involved in almost every major melanoma study and personally presented the 'CheckMate-76K' trial results on Opdivo at ESMO. She’s a prominent figure in the field and also serves on our scientific advisory board. During our meeting, she expressed interest in leading the clinical trials for GI-102's approval in melanoma. We plan to finalize the necessary procedures after returning to Korea."

"In our meetings, we shared phase 1 data for GI-102 as a monotherapy. Some attendees mistook the results for a combination therapy due to the strong anticancer activity we observed. GI-102 showed a partial response in 43% of melanoma patients who had previously failed immunotherapy.

This result stands out when compared to combination therapies like Opdivo with RP1, which showed an ORR of 34%, and nivolumab with ipilimumab, which demonstrated an ORR of 39%. GI-102's monotherapy performance exceeded expectations, driving interest from global pharmaceutical companies."

"In addition to GI-101A and GI-102, we recently submitted an Investigational New Drug (IND) application for GI-108 (a CD73 antibody-IL2v fusion protein) for a phase 1 trial in Korea.

The decision to submit this IND was the result of extensive discussions with Medirama's CEO, Dr. Hanlim Moon, with whom we are co-developing GI-108. We carefully reviewed the preclinical package and clinical development strategy. The trial is designed as a phase 1/2a study, targeting cancers such as EGFR-mutant non-small cell lung cancer, pancreatic cancer, and esophageal cancer, all of which exhibit high CD73 expression.

GI-108, a fourth-generation metabolic immuno-oncology drug, combines an antibody targeting CD73, which is overexpressed on cancer cells, with the anticancer agent IL-2. This dual-targeting approach allows it to specifically attack cancer cells, effectively "starving" them, much like a missile targeting only its intended target. The mechanism of action is similar to that of an antibody-drug conjugate (ADC).

However, CD73 plays a crucial role in the cancer growth process by secreting a substance called 'adenosine.' The problem with adenosine is that it can deactivate immune cells with anticancer activity.

AstraZeneca has conducted a promising phase 2 trial combining the CD73 antibody 'oleclumab' with Imfinzi in PD-L1 low-expressing non-small cell lung cancer, which is typically resistant to immunotherapy. In preclinical trials, GI-108 showed significantly enhanced immune cell activity, even in environments with high adenosine levels, compared to oleclumab."

"Through research published in Gastroenterology, I demonstrated that obesity and insulin resistance can be modulated by immune cells. As an immunologist, I’ve always been interested in obesity alongside cancer and allergies.

Our obesity treatment, currently in development, is a dual fusion protein that promotes fat breakdown, increases energy expenditure, and enhances muscle growth. Unlike conventional appetite-suppressing treatments, our approach offers a differentiated mechanism for weight reduction. We plan to share more details soon.

We’re actively out-licensing our allergy treatment candidate GI-301 in collaboration with Yuhan Corporation. We’re also focused on securing accelerated approval for GI-102 from the U.S. FDA, following our productive meetings at ESMO. We hope to bring positive news soon."