Ascentage Pharma Announces IND Clearance by the U.S. Food and Drug Administration for BTK Degrader APG-3288

Rhea-AI Summary

Ascentage Pharma (NASDAQ:AAPG) announced that the U.S. FDA has granted IND clearance for APG-3288, a next-generation BTK-targeted protein degrader, enabling a global, multicenter, open-label Phase I study in patients with relapsed/refractory B-cell malignancies.

APG-3288 is a PROTAC-designed degrader intended to remove wild-type and multiple mutant BTK proteins, with preclinical data claiming higher potency, selectivity, and favorable PK versus other BTK degraders; clinical evaluation will assess safety, tolerability, PK, and preliminary efficacy.

Positive

• FDA IND clearance granted for APG-3288
• Planned global, multicenter Phase I study for relapsed/refractory B-cell malignancies
• Degrades wild-type and multiple BTK mutants linked to inhibitor resistance
• Preclinical data claim higher potency, selectivity, and favorable PK

Negative

• No human clinical efficacy data; first-in-human Phase I only
• APG-3288 not approved by the U.S. FDA and remains investigational
• Safety and tolerability in patients not yet established

Market Reality Check

$28.22 Last Close

Volume Volume 4,792 is 1.17x the 20-day average of 4,085 ahead of this news. normal

Technical Shares at 26.01 were trading below the 200-day MA of 32.56 and 46.32% below the 52-week high.

Peers on Argus

Biotech peers showed mixed moves, with MIRM up 1.84% and ACAD up 1.66% while ZLAB and ARWR were down 1.14% and 1.74%, suggesting AAPG’s -3.49% move was more stock-specific than sector-driven.

Historical Context

Date	Event	Sentiment	Move	Catalyst
Dec 17	Investor conference	Neutral	-3.1%	J.P. Morgan Healthcare Conference presentation announcement and investor outreach plans.
Dec 08	Clinical data update	Positive	-4.0%	Four-year registrational Phase II olverembatinib data in TKI-resistant/intolerant CML-CP.
Dec 08	Clinical data update	Positive	-4.0%	Updated ASH 2025 second-line CP-CML data showing high response rates.
Dec 08	Clinical data update	Positive	-4.0%	First dataset from Phase III POLARIS-1 in newly diagnosed Ph+ ALL.
Dec 07	Clinical data update	Positive	-4.8%	Phase Ib/II lisaftoclax combination data in venetoclax‑exposed myeloid malignancies.

Pattern Detected

Recent clinically positive or strategically neutral news has often coincided with short-term share price declines.

Recent Company History

Over the past months, Ascentage Pharma has highlighted multiple hematology-oncology updates, including ASH 2025 data for olverembatinib and lisaftoclax and participation in investor conferences. These events featured favorable efficacy and safety readouts and strategic visibility efforts yet were followed by share declines of about 3–5%. The current FDA IND clearance for BTK degrader APG-3288 extends this pattern of clinically or strategically positive milestones occurring while the stock trades well below its 52-week high.

Market Pulse Summary

This announcement highlights FDA IND clearance for BTK degrader APG-3288, enabling a global Phase I study in relapsed/refractory B-cell and other hematologic malignancies. It extends Ascentage Pharma’s focus beyond prior ASH 2025 datasets for olverembatinib and lisaftoclax. Investors may track enrollment progress, early safety and efficacy signals, and how this BTK degrader complements existing small‑molecule agents as the stock trades well below its 52-week high and under the 200-day MA.

Key Terms

bruton tyrosine kinase medical

"Bruton tyrosine kinase (BTK)-targeted protein degrader APG-3288 has received"

Bruton tyrosine kinase (BTK) is a protein inside certain immune cells that acts like a control switch, helping those cells receive signals that tell them to grow, divide, or produce antibodies. It matters to investors because medicines that block or modify BTK can treat blood cancers and autoimmune diseases, so clinical results, regulatory decisions, or patent news about BTK-targeting drugs can materially affect the value of companies developing those therapies.

btk medical

"BTK is a key kinase in the B-cell receptor (BCR) signaling pathway"

Bruton's tyrosine kinase (BTK) is an enzyme that acts like a light switch inside certain immune and blood cells, helping them send signals that control growth, survival and activity. Investors care because medicines that block or modify BTK can change how cancers and autoimmune diseases are treated; clinical trial results, safety profiles and regulatory decisions for BTK-targeting drugs can materially alter a biotech or pharmaceutical company’s prospects and valuation.

investigational new drug (ind) regulatory

"has received investigational new drug (IND) clearance from the U.S. FDA"

An investigational new drug (IND) is a drug or biologic that is being tested but has not yet been approved for general use; it is the application and formal status that allows a company to begin human clinical trials under regulator oversight. Investors care because an IND marks the transition from lab work to human testing — like getting a permit to run real-world experiments — which creates important milestones, costs, timelines and regulatory risk that drive a development-stage company's value.

proteolysis-targeting chimera (protac) medical

"developed utilizing Ascentage Pharma’s proprietary proteolysis-targeting chimera (PROTAC) technology"

A proteolysis-targeting chimera (PROTAC) is a lab-designed molecule that links a disease-causing protein to the cell’s natural disposal system so the protein is tagged and destroyed rather than merely blocked. For investors, PROTACs represent a new drug approach that can tackle proteins traditional drugs cannot, potentially offering more durable effects and new market opportunities, but they also carry development and regulatory risk common to novel therapies.

b-cell receptor (bcr) signaling pathway medical

"BTK is a key kinase in the B-cell receptor (BCR) signaling pathway"

The B‑cell receptor (BCR) signaling pathway is the chain of molecular signals that tells a B cell—an immune cell—when to activate, grow, make antibodies, or survive, comparable to a phone line that carries orders inside a cell. It matters to investors because abnormal or overactive BCR signaling is a driver of some cancers and autoimmune diseases, making components of this pathway important drug targets, biomarkers, and potential value drivers for biotech and pharmaceutical companies.

hematologic malignancies medical

"in patients with relapsed/refractory hematologic malignancies"

Hematologic malignancies are types of cancers that start in the blood or the organs responsible for blood production, like the bone marrow and lymph nodes. They matter because they can disrupt normal blood functions, leading to issues like weakness, infections, or abnormal growths, and often require specialized treatments.

e3 ubiquitin ligase medical

"the PROTAC, and the Cereblon E3 ubiquitin ligase, leading to proteasome-mediated"

An e3 ubiquitin ligase is a specialized enzyme that acts like a labeler, attaching small protein tags called ubiquitin to other proteins to mark them for disposal or to change how they behave. For investors, these enzymes matter because they control biological pathways tied to disease and aging, making them attractive drug targets or diagnostic markers; therapies that boost or block specific e3 ligases can create new treatment opportunities and commercial value.

pharmacokinetic (pk) profile medical

"designed to evaluate the safety, tolerability, pharmacokinetic (PK) profile, and preliminary efficacy"

A pharmacokinetic (pk) profile shows how a drug moves through a person's body over time, including how quickly it is absorbed, how much of it stays in the system, and how it is eliminated. For investors, understanding this profile helps assess how effectively and safely a medication works, which can impact a company’s potential success and market value. It’s like tracking how a drop of dye spreads and fades in a glass of water to see how it disperses.

AI-generated analysis. Not financial advice.

• Novel next-generation Bruton tyrosine kinase (BTK)-targeted protein degrader APG-3288 has received investigational new drug (IND) clearance from the U.S. FDA, marking another major expansion to the company’s global innovative pipeline.
• Ascentage Pharma will conduct a global Phase I study evaluating APG-3288 in patients with relapsed/refractory B-cell malignancies.

ROCKVILLE, Md. and SUZHOU, China, Jan. 06, 2026 (GLOBE NEWSWIRE) -- Ascentage Pharma Group International (NASDAQ: AAPG; HKEX: 6855), a global, commercial stage, integrated biopharmaceutical company engaged in the discovery, development and commercialization of novel, differentiated therapies to address unmet medical needs in cancer, announced that its novel next-generation BTK-targeted protein degrader, APG-3288, has received the IND clearance from the U.S. Food and Drug Administration (FDA) and is poised to enter a clinical study in patients with relapsed/refractory B-cell malignancies. This clearance officially opens the chapter on Ascentage Pharma’s clinical development in the field of targeted degradation and marks another major expansion to the company’s global innovative pipeline.

This is a global, multicenter, open-label Phase I study designed to evaluate the safety, tolerability, pharmacokinetic (PK) profile, and preliminary efficacy of APG-3288 in patients with relapsed/refractory hematologic malignancies.

BTK is a key kinase in the B-cell receptor (BCR) signaling pathway and plays a central role in the activation, proliferation, and survival of B-cells. Aberrant BTK activation is closely associated with the initiation and progression of multiple B-cell malignancies such as B-cell lymphoma (including diffuse large B-cell lymphoma, mantle cell lymphoma, and follicular lymphoma), chronic lymphocytic leukemia (CLL), and Waldenström's macroglobulinemia (WM)¹. Beyond oncology indications, BTK also plays a critical role in both BCR- and Fc receptor-mediated signal transduction in innate immune cells. As a result, the aberrant activation of BTK has been implicated in the pathogenesis of various autoimmune and inflammatory diseases². BTK inhibitors have drastically improved treatment outcomes for patients with B-cell malignancies. However, BTK mutations and remodeling of signaling pathways often lead to acquired resistance during prolonged treatment. There remains an urgent clinical need for new drugs promising novel mechanisms of action³.

APG-3288 is the first novel, highly potent and selective BTK degrader developed utilizing Ascentage Pharma’s proprietary proteolysis-targeting chimera (PROTAC) technology platform. This candidate induces the formation of a ternary complex consisting of the BTK target, the PROTAC, and the Cereblon E3 ubiquitin ligase, leading to proteasome-mediated degradation of the BTK target. Unlike conventional BTK inhibitors, APG-3288 is designed to act through degradation rather than inhibition, inducing rapid, potent, highly selective, and sustained degradation of both wild-type BTK and multiple BTK mutants associated with resistance to existing BTK inhibitors. Critically, this approach blocks the BCR-BTK signaling axis at its source, thereby overcoming resistance to BTK inhibitors and potentially providing a novel and differentiated therapeutic strategy for BTK-targeted treatment⁴.

In preclinical studies, compared to other BTK degraders in development, APG-3288 demonstrated more potent BTK degradation, higher selectivity, and more favorable PK properties that highlighted the drug’s potential⁵.

Yifan Zhai, M.D., Ph.D., Chief Medical Officer of Ascentage Pharma, said, “Compared to existing conventional BTK inhibitors, Ascentage Pharma’s BTK degraders developed with our PROTAC technology can achieve complete degradation of target protein and are enabled by a molecular mechanism that can induce stronger efficacy. APG-3288 represents a strategic clinical stage candidate in the field of BTK-targeted therapies. Its high selectivity, potency, and consistent PK/PD profiles across multiple BTK-resistant models fully validate our differentiated design capabilities of PROTAC-based therapeutic candidates. This FDA clearance marks a major milestone for the development of APG-3288 and strategic pipeline expansion that underscores our persistent innovation in the field of hematologic malignancies. It also lays a strong foundation for our future exploration of the combinatory potential between APG-3288 and our existing proprietary small-molecule agents. We plan to accelerate the global clinical development of APG-3288 and actively explore the therapeutic potential of protein degraders in hematologic malignancies and other BTK-driven diseases, with the goal of bringing more new treatment options to patients as soon as possible.”

*APG-3288 is currently under investigation and has not been approved by the U.S. FDA

References:
[1]. Pal Singh, S., F. Dammeijer, and R.W. Hendriks, Role of Bruton’s tyrosine kinase in B cells and malignancies. Molecular Cancer, 2018. 17(1).
[2]. Mirre De Bondt, Janne Renders, Sofie Struyf, Niels Hellings, Inhibitors of Bruton's tyrosine kinase as emerging therapeutic strategy in autoimmune diseases Autoimmunity Reviews, Volume 23, Issue 5, 2024.
[3]. Wang, E., et al., Mechanisms of Resistance to Noncovalent Bruton’s Tyrosine Kinase Inhibitors. New England Journal of Medicine, 2022. 386(8): p. 735-743.
[4]. Zhang, D., et al., NRX-0492 degrades wild-type and C481 mutant BTK and demonstrates in vivo activity in CLL patient-derived xenografts. Blood, 2023. 141(13): p. 1584-1596.
[5]. Wu, Y., et al., Translational modelling to predict human pharmacokinetics and pharmacodynamics of a Bruton's tyrosine kinase‐targeted protein degrader BGB‐16673. British Journal of Pharmacology, 2024. 181(24): p. 4973-4987.

About Ascentage Pharma
Ascentage Pharma Group International (NASDAQ: AAPG; HKEX: 6855) (“Ascentage Pharma” or the “Company”) is a global, commercial stage, integrated biopharmaceutical company engaged in the discovery, development and commercialization of novel, differentiated therapies to address unmet medical needs in cancer. The Company has built a rich pipeline of innovative drug products and candidates that includes inhibitors targeting key proteins in the apoptotic pathway, such as Bcl-2 and MDM2-p53, as well as next-generation kinase inhibitors.

The lead asset, Olverembatinib, is the first novel third-generation BCR-ABL1 inhibitor approved in China for the treatment of patients with CML in chronic phase (CML-CP) with T315I mutations, CML in accelerated phase (CML-AP) with T315I mutations, and CML-CP that is resistant or intolerant to first and second-generation TKIs. All indications are covered by the China National Reimbursement Drug List (NRDL). The Company is currently conducting an FDA-cleared, global registrational Phase III trial, or POLARIS-2, of Olverembatinib for CML, as well as global registrational Phase III trials for patients with newly diagnosed Ph+ ALL and SDH-deficient GIST patients.

The Company’s second approved product, Lisaftoclax, is a novel Bcl-2 inhibitor for the treatment of various hematologic malignancies. Lisaftoclax is being commercialized in China following National Medical Products Administration (NMPA) approval for the treatment of adult patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) who have previously received at least one systemic therapy including BTK inhibitors. The Company is currently conducting four global registrational Phase III trials: the FDA-cleared GLORA study of Lisaftoclax in combination with BTK inhibitors in patients with CLL/SLL previously treated with BTK inhibitors for more than 12 months with suboptimal response; the GLORA-2 study in patients with newly diagnosed CLL/SLL; the GLORA-3 study in newly diagnosed, elderly and unfit patients with acute myeloid leukemia (AML); and the GLORA-4 study in patients with newly diagnosed higher-risk myelodysplastic syndrome (HR MDS), a study that was simultaneously cleared by the U.S. FDA, the EMA of the EU, and China CDE.

Leveraging its robust R&D capabilities, Ascentage Pharma has built a portfolio of global intellectual property rights and entered into global partnerships and other relationships with numerous leading biotechnology and pharmaceutical companies, such as Takeda, AstraZeneca, Merck, Pfizer, and Innovent, in addition to research and development relationships with leading research institutions, such as Dana-Farber Cancer Institute, Mayo Clinic, National Cancer Institute and the University of Michigan. For more information, visit https://ascentage.com/.

Forward-Looking Statements
This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 and Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. All statements, other than statements of historical facts, contained in this press release may be forward-looking statements, including statements that express Ascentage Pharma’s opinions, expectations, beliefs, plans, objectives, assumptions or projections regarding future events or future results of operations or financial condition.

These forward-looking statements are subject to a number of risks and uncertainties as discussed in Ascentage Pharma’s filings with the SEC, including those set forth in the sections titled “Risk factors” and “Special note regarding forward-looking statements and industry data” in its Registration Statement on Form F-1, as amended, filed with the SEC on January 21, 2025, and the Form 20-F filed with the SEC on April 16, 2025, the sections headed “Forward-looking Statements” and “Risk Factors” in the prospectus of the Company for its Hong Kong initial public offering dated October 16, 2019, and other filings with the SEC and/or The Stock Exchange of Hong Kong Limited we made or make from time to time that may cause actual results, levels of activity, performance or achievements to be materially different from the information expressed or implied by these forward-looking statements. The forward-looking statements contained in this presentation do not constitute profit forecast by the Company’s management.

As a result of these factors, you should not rely on these forward-looking statements as predictions of future events. The forward-looking statements contained in this press release are based on Ascentage Pharma’s current expectations and beliefs concerning future developments and their potential effects and speak only as of the date of such statements. Ascentage Pharma does not undertake any obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise.

Contacts

Investor Relations:
Stella Yang
Ascentage Pharma
Stella.Yang@ascentage.com
+1 (301) 792-6286

Stephanie Carrington
ICR Healthcare
AscentageIR@icrhealthcare.com
+1 (646) 277-1282

Media Relations:
Sean Leous
ICR Healthcare
AscentagePR@icrhealthcare.com
+1 (646) 866-4012

FAQ

What did Ascentage Pharma announce about APG-3288 (AAPG) on January 7, 2026?

The company announced U.S. FDA IND clearance for APG-3288 to start a global Phase I study in relapsed/refractory B-cell malignancies.

What is the design and goal of the APG-3288 (AAPG) clinical study?

A global, multicenter, open-label Phase I study to evaluate safety, tolerability, pharmacokinetics, and preliminary efficacy.

How does APG-3288 (AAPG) differ from conventional BTK inhibitors?

APG-3288 is a PROTAC BTK degrader designed to remove BTK protein rather than inhibit it, including certain resistance-associated mutants.

Does APG-3288 (AAPG) have clinical approval from the U.S. FDA?

No. APG-3288 is investigational and has not been approved by the U.S. FDA.

What preclinical advantages did Ascentage report for APG-3288 (AAPG)?

The company reported more potent BTK degradation, higher selectivity, and favorable PK versus other BTK degraders in preclinical studies.

Which patient population will the APG-3288 (AAPG) Phase I trial enroll?

Patients with relapsed or refractory B-cell malignancies, including lymphomas and CLL as described.