Hejiao Pharmaceuticals will present the latest data from the CPI-818 Phase I/Ib clinical trial at the ASH Annual Meeting

On December 12, Hejiao Pharmaceuticals, a clinical-stage innovative drug company, announced the latest results of the Phase I/Ib global clinical trial of CPI-818, the world's first in class innovative drug ITK inhibitor, jointly developed with Corvus Pharmaceuticals, demonstrating its antitumor activity in patients with T-cell lymphoma (TCL) and its therapeutic potential
in Th2 and Th17-mediated autoimmune and allergic diseases 。 The data will be presented today in poster format at the 64th Annual Meeting of the American Society of Hematology (ASH), which took
place in a combination of online and offline from December 10-13, 2022.

"CPI-818 ITK inhibitors have demonstrated monotherapy antitumor activity in patients with refractory T-cell lymphoma who have extremely limited treatment options and extremely low
response rates.
" Dr.
Richard Miller, co-founder and chairman of Hejiao Pharmaceutical, said, "We have seen sustained objective responses
in 4 of 11 evaluable patients in the 200 mg dose group.
Based on the current clinical trial results, Hejiao Pharmaceutical and Corvus Pharmaceuticals plan to advance CPI-818 to the global phase II clinical trial of T-cell lymphoma in mid-2023, the incidence and prevalence of T-cell lymphoma in China is relatively high, and Hejiao Pharmaceutical will conduct some clinical trial research
in China.
Phase I data also provide in vivo evidence that CPI-818 regulates immune function
in T cells by inducing Th1 cell skew and blocking Th2 and Th17 cells.
These effects are important for cancer treatment – Th1 cells are essential for eliminating tumor cells – but also include many autoimmune and allergic diseases
in which Th2 and Th17 cells are involved.
The results of clinical and preclinical studies reported in ASH suggest that CPI-818 enhances anti-tumor immunity and represents a potential new approach
to immunotherapy.
"

Dr.
Miller concluded, "Overall, we believe that the data presented at ASH provide a solid theoretical basis
for ITK inhibitors for the treatment of lymphoma and some immune diseases.
CPI-818 is the world's first clinical-stage ITK inhibitor with high selectivity for ITK, which we believe is essential to achieve the immunomodulatory function observed in the study and represents a significant achievement
for our R&D team 。 Dr.
Wang Tiefei, co-founder of Hejiao Pharmaceutical, said: "The successful development of CPI-818 global clinical phase I/Ib fully demonstrates the complementary advantages and resource sharing advantages of Hejiao Pharmaceutical and Corvus Pharmaceuticals in the joint development process, and looks forward to the continued cooperation between the two parties to efficiently promote the global development process
of CPI-818.
"

Professor Yuqin Song, a leading investigator of CPI-818 clinical phase I/Ib in China and a lymphoma department at Peking University Cancer Hospital, said: "As the world's first ITK inhibitor to enter the clinical stage, the existing data in phase I/Ib have proved its safety and certain monotherapy anti-tumor activity, and at the same time obtained in vivo evidence that CPI-818 can regulate the immune function of T cells, which is very promising
in tumor immunotherapy.
It is hoped that the follow-up development of CPI-818 will be smooth and bring good news to Chinese T-cell lymphoma patients as soon as possible.
"

Key results of the CPI-818 Phase I/Ib clinical trial were announced at ASH 2022

CPI-818 is ongoing in Phase I/Ib clinical trials for monotherapy in patients with relapsed TCL
.
As of September 2, 2022, a total of 43 patients have participated in the trial, divided into four dose-escalation cohorts: doses of 100, 200, 400, and 600 mg twice
daily.
The plasma drug concentration provided by the 200 mg dose was found to achieve the best effect on in vitro T cell differentiation and correspondingly elicit the most frequent and durable tumor response
in the body.
This is therefore the optimal dose selected, and more patients are being recruited to participate in clinical trials
of the 200 mg dose cohort.
The endpoints of Phase I/Ib clinical trials were safety, pharmacokinetics (PK), immune effects, and tumor response
.

Interim data highlights for T-cell lymphoma

● Thirteen patients were enrolled in the 200 mg cohort, of which 11 were evaluable responses, all were severely treated patients, received an average of 3 lines of prior therapy, and 4 of 11 patients had overall objective responses
。 In this group, one patient with peripheral T-cell lymphoma (PTCL) achieved a complete response (CR) lasting 25 months; Lymph node CR in a patient with cutaneous T-cell lymphoma lasting 19 months; In patients with PTCL and anaplastic large cell lymphoma, two sustained partial remissions (PRs)
were seen at 6 and 8 months follow-up, respectively.

● No dose-limiting toxicity was observed and the maximum tolerated dose
was not reached at doses up to 600 mg twice daily.

● All of the above data is as of September 2, 2022
.

Interim data highlights of immune efficacy

● As of September 2, 2022, according to peripheral blood samples from several patients, the optimal dose of 200 mg can induce Th1 deviation, Th2 and Th17 blockade:

- In a patient with a significant reduction in a large abdominal wall tumor, blood sample analysis showing increased blood Th1, decreased blood Th17, and decreased eosinophil count and IL-5 secretion were consistent
with Th1 deviation and Th2 blockade.
Analysis of tumor samples from this patient revealed an increase in terminally differentiated T effector memory cells (TEMRA cells) with antigen-presenting functions and mediating effects, such as destroying tumor cells
.

- In four additional patients (two patients with PR, one patient with stable disease (SD) and one patient with disease progression (PD)), changes
in Th1 and CD8+ TEMRA cells were measured over time.
PR and SD patients show increased Th1 and CD8+ TEMRA cells Notably, patients with SD and PD had lymphopenia at baseline: absolute count <1,000, indicating that the patient needed to have at least a minimum level of immunity
.

● In vitro dose-dependent test data suggest that CPI-818 has Th1-biasing and Th2-blocking effects
at a 200 mg dose.
This included analysis of peripheral blood samples from 12 healthy volunteers, studies at different concentrations of CPI-818, and other studies showing that CPI-818 inhibits normal CD4+ and Sezary cell production of Th2 cytokines
.

● Other in vitro studies have shown that CPI-818 inhibits the production of interleukins 4, 5, and 13; Cytokines
produced by Th2 cells.

● In vivo preclinical studies in mice transplanted with T-cell lymphoma have shown that CPI-818 causes increased CD8+ T cell infiltration in tumors and inhibits tumor growth
.

● Human and preclinical findings suggest that CPI-818 enhances anti-tumor immunity and represents a potential new approach
to immunotherapy.

Conference calls, webcasts, and presentation slides

The conference call and webcast will be held on Tuesday, December 13, 2022 at 5:30 a.
m.
Beijing time (Monday, December 12, 2022 from 4:30 to 5:30 p.
m.
ET) to provide an overview
of the CPI-818 data presented at the ASH conference.
Call 1-877-300-8521 (toll-free within the U.
S.
) or 1-412-317-6026 (international) and use the conference ID 10172958 participate in the conference call
.

About CPI-818

CPI-818 is a small molecule oral drug in research that selectively inhibits ITK (interleukin-2-induced T cell kinase)
in clinical studies.
It is designed to stop malignant T cell growth and regulate the immune response
.
ITK is an enzyme expressed primarily on T cells and plays a role
in T cell and natural killer (NK) cell lymphoma and leukemia, as well as normal immune function.
Recent clinical data on T-cell lymphoma suggest that CPI-818 has the potential to
control T-helper cell differentiation and enhance the immune response to tumors.
Interference with ITK signaling can also modulate the immune response
to various antigens.
CPI-818 affects T cell differentiation and induces the production of Th1 helper cells at optimal doses that have been explored, while blocking the development of Th2 and Th17 cells and the production
of Th2-related cytokines.
Th1 T cells are required for
tumor immunity, viral infections, and other infectious diseases.
Th2 and Th17 helper T cells are involved in the pathogenesis
of many autoimmune and allergic diseases.
The highly selective ITK of CPI-818 mediates the skew
of immune effects towards Th1.
Harmony believes that inhibition of specific molecular targets in T cells may benefit patients with T-cell lymphoma and leukemia, as well as autoimmune and allergic diseases
.
Hutchipharma is conducting Phase I/Ib trials in patients with relapsed/refractory T-cell lymphoma to select the optimal dose of CPI-818 and evaluate its safety, pharmacokinetics, target occupancy, immune effects, biomarkers and efficacy
.
Interim data from the Phase I/Ib clinical trial of CPI-818 for the treatment of T-cell lymphoma showed remission in patients with very advanced, relapsed and refractory T-cell malignancies and determined the dose
that maximally affected T-helper cell differentiation.

Current treatment for peripheral T-cell lymphoma

PTCL lymphoma is a highly heterogeneous group of diseases
.
In general, the prognosis is poor, with a 5-year survival rate of 11%
in high-risk patients.
Patients with relapse have a median overall survival of approximately 6 months and a median progression-free survival of less than 3 months
.
Initial treatment is based on chemotherapy, with bone marrow transplantation
in young patients who are likely to achieve remission.
In patients with relapsed and refractory treatment, currently approved regimens are virulent and generally have a low response rate of only 25 to 30%, with a median progression-free survival of 4 to 5 months
.
Because of these factors, the National Comprehensive Cancer Network (NCCN) guidelines recommend that patients with relapsed and refractory treatment be prioritized for drug clinical trials, suggesting that there is currently a need for safer and more effective treatments
for the clinical treatment of peripheral T-cell lymphoma.