Tianyan Pharmaceutical announced the clinical data of ADG116, an anti-CTLA-4 neotope anti-CTLA-4 epitope, at SITC 2022, demonstrating highly differentiated safety and anti-tumor activity for patients with refractory tumors treated with multiple lines

Tianyan Pharmaceuticals (the "Company" or "Tianyan ") (NASDAQ: ADAG) is a platform-driven, clinical-stage biopharmaceutical company dedicated to the discovery and development of novel cancer immunotherapies
based on original antibodies.
On November 11, the company announced that it presented two posters at the 37th American Society for Cancer Immunotherapy (SITC) Annual Meeting in Boston to announce data from its anti-CTLA-4 neotope antibody NEObody™ADG116 1b/2 trial
.

The poster is the first poster of the "Phase 1b/2 Study of NEObody™ADG116 Monotherapy and Combination with Teripulimab in Patients with Advanced/Metastatic Solid Tumors" to present data from a Phase 1b/2 open-label dose-escalation versus dose expansion trial evaluating the safety and efficacy of ADG116 in monotherapy and in combination with teripulimab in patients with advanced metastatic solid tumors undergoing multiple lines of therapy
。

The published trial data included 50 patients who climbed the slope with a single agent, of which 24 patients received doses less than or equal to 6 mg/kg, 23 patients received doses of 10 mg/kg, and 3 patients received doses of 15 mg/kg, based on widely recognized dose-dependent toxicity of CTLA-4 targets, and toxicity problems after repeated administration, which provide a solid basis
for evaluating the safety of ADG116 。 Of the efficacy assessments covering more than 20 different tumor types, the majority of patients (64%) had received at least three or more lines of treatment, and more than 1/3 (36%) had previously undergone immuno-oncology (IO) therapy with disease progression
.
Nearly half (44%) of the nine patients treated with ADG116 in combination with anti-PD-1 teripulimab underwent multiple lines of therapy, and nearly half (44%) had received at least three or more lines of therapy
.

Key figures as of September 19, 2022 include:

● ADG116 monotherapy demonstrates a credible and highly differentiated safety profile, with a climbing dose of up to 15 mg/kg: ADG116 is well tolerated
at all dose levels and during repeated administration.
Of these, only 3 (6%) patients observed grade 3/4 treatment-related adverse events (TRAEs) and 28 (56%) patients observed grade 1/2 treatment-related adverse events (TRAEs).

In the same cohort at the 10 mg/kg dose level, the overall incidence of treatment-related adverse events (TRAEs) of grade 3 or above was observed in 13%
after repeated dosing and tracking of late toxicity.
For reference, the currently approved anti-CTLA-4 therapy ipilimumab has observed grade 3 or greater treatment-related adverse events (TRAEs) at a dose level of 10 mg/kg in first-line monotherapy for melanoma ^{patients [1].}

At a dose level of 15 mg/kg for ADG116 monotherapy, no treatment-related adverse events (TRAEs)
of grade 3 or higher were observed.

●Monotherapy demonstrates initial efficacy in patients treated with multiple lines of therapy: Of the 36 patients with evaluable efficacy, three received ADG116 monotherapy at a dose level of 15 mg/kg, and one patient with Kaposi sarcoma observed initial tumor remission
after two rounds of treatment.
The overall disease control rate (DCR) was 33% for all monotherapy dose groups, and narrowing
of tumor target lesions was observed in both cold and hot tumor patients.

Of particular note is the observation of a partial remission of a treated tumor in an additional patient with renal cell carcinoma who had previously progressed
after receiving two therapies, including anti-PD-L1 inhibitors, as of 2 November 2022.
The patient received 4 cycles of ADG116 monotherapy at a dose level of 10 mg/kg and no treatment-related adverse events (TRAEs)
of grade 3 or higher were observed.

● Optimization of the dose of combination therapy: ADG116 was administered 3 mg/kg or 6 mg/kg every three weeks in combination with 240 mg teripulimab (N=9).

。 Although the combination therapy with teripulimab at the ADG116 6 mg/kg dose has not reached the target toxicity level (TTL) (i.
e.
, the incidence of treatment-related adverse events (TRAEs) of grade 3 or above is lower compared with approved anti-CTLA-4 and anti-PD-1 combination therapy), treatment with teripulimab administered every three weeks at the ADG116 3 mg/kg dose level is controllable in the TTL range, and has shown impressive efficacy
in refractory tumors.
Further dosing optimization is planned, including extending dosing intervals to six weeks and continuing to evaluate the combined efficacy of ADG116 with teripulimab to meet required TTL
.

● Combination therapy for cold tumors has shown potential efficacy, and one patient with head and neck cancer has been confirmed to achieve sustained complete remission, which is noteworthy: Of the seven patients who can assess the efficacy of combination therapy, one patient with platinum-resistant recurrent head and neck squamous cell carcinoma has been confirmed to achieve sustained complete tumor remission
。 The patient received ADG116 in combination with teripulimab at a dose level of 3 mg/kg and was one of five patients in this dose-level group who could assess efficacy by the cut-off date (objective response rate 20%; For patients with refractory tumors who have previously undergone multiple lines of therapy, the disease control rate is 100%)
.
After two rounds of treatment, the lesion completely disappeared; After six rounds of treatment, the tumor remained in complete remission
.

The poster is the second poster entitled "Preliminary Update on the Phase 1b/2 Open-label, Dose-Escalation, and Expansion Study of the Anti-CTLA-4 Neoepitope NEObody™ADG116 in combination with pembrolizumab in patients with advanced/metastatic solid tumors" reports safe and potentially effective dose levels
in combination therapy with ADG116 and pembrolizumab.

The evaluation data of ADG116 in combination with pembrolizumab in six patients with predominantly cold tumors who underwent multi-line therapy further confirmed the safety and potential efficacy
of ADG116 when combined with pembrolizumab at a dose of 3 mg/kg once every three weeks.
No treatment-related adverse events above grade 3 were observed during the trial, nor were dose-limiting toxic events
observed.

In addition, the carcinoembryonic antigen (CEA) indexes in two patients with metastatic microsatellite stable (MSS) colorectal cancer (CRC) decreased significantly, by 43% and 27%,
respectively.
Both patients had liver or lung metastases and continued treatment
.
Data from this trial support continued evaluation of the efficacy
of ADG116 in combination with pembrolizumab, anti-CTLA-4 and anti-PD-1 in refractory tumors such as microsatellite-stabilized metastatic colorectal cancer (MSS-CRC).

"Current clinical data provide critical and convincing clinical evidence
that the new epitope ADG116 enhances the anti-CTLA-4 blocking effect by targeting a unique epitope that is highly conserved with CTLA-4, and improves the efficacy and safety of monotherapy and in combination with PD-1 。 "Further optimization of the effective dose of ADG116 and its masked version ADG126 in combination with PD-1 will facilitate the clinical development
of oncology indications that have demonstrated initial efficacy but existing anti-CTLA-4 therapies have not been approved or ineffective.
" "

For details, please visit the published literature page of the company's official website to view the relevant poster

References:

1 Ascierto PA, et al.
J Immunother Cancer 2020; 8:e000391.
doi:10.
1136/jitc-2019-000391