On March 27, 2024 OSE Immunotherapeutics SA (ISIN: FR0012127173; Mnemo: OSE) reported its consolidated annual financial results for 2023 and provided an update on key proprietary clinical and preclinical achievements, on ongoing collaboration and licensing agreements, as well as on the 2024 Company’s outlook (Press release, OSE Immunotherapeutics, MAR 27, 2024, View Source [SID1234641520]).

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Nicolas Poirier, Chief Executive Officer of OSE Immunotherapeutics, commented: "The Company has built today a broad and independent portfolio of five clinical assets, three pharmaceutical partnerships and three research platforms, all with potential key milestones expected in 2024. We have achieved significant steps in 2023 and all of which put in place during this year will help advance our key priorities on our clinical and preclinical stage products in immuno-oncology and inflammation in the coming months. We started 2024 with a major achievement for the Company’s growth as we also reinforced our financial resources with a new license and collaboration agreement with AbbVie valued up to $713 million, including a $48 million upfront payment, in line with our business-model of recurrent and strategic pharmaceutical partnerships. We will advance the Company’s clinical programs and continue investing in our R&D drug discovery engine to identify novel therapeutics for patients with high medical need in inflammation, autoimmune diseases and immuno-oncology.

The conduct of our Tedopi new pivotal Phase 3 clinical program in second-line non-small cell lung cancer, in patients with secondary/acquired resistance, is on track. Two dossiers were filed to the Food & Drug Administration (FDA) end of 2023: a companion test to identify HLA-A2 positive cancer patients eligible (collaboration with the company GenDx) and a clinical protocol. Both dossiers were approved mid-January 2024 and will be filed in Europe in the coming weeks.

Completion of patient enrollment in the Phase 2 trial evaluating Lusvertikimab in ulcerative colitis was recently announced, and we are now eagerly looking forward to the top-line efficacy results after the induction phase and first early assessment after 6 months of therapy expected mid-2024.

The ongoing Phase 1/2 trial with proprietary anti-PD1 OSE-279 in solid tumors has confirmed positive clinical efficacy results with a high anti-tumor response rate in difficult-to-treat patients. These results encourage further clinical development in the future, used in monotherapy in already identified cancer niche indications and to explore combinations with OSE drug candidates, in particular with our neo-epitope cancer vaccine.

The positive interim data analysis from the FIRsT Phase 1/2 study evaluation of anti-CD28 FR104/VEL-101 in renal transplant marks a key advancement in the clinical development towards a Phase 2 trial under preparation by our partner Veloxis Pharmaceuticals.

Two clinical drug-candidates, BI 765063 and BI 770371, from our selective SIRPa myeloid checkpoint technology are being evaluated by Boehringer Ingelheim in combination in cancer patients, in particular in metastatic or recurrent head and neck squamous cell carcinoma (HNSCC) and hepatocellular carcinoma (HCC). Promising results from the first Phase 1 study, with early clinical efficacy data and biomarkers predictive of response and survival, were presented at the 2023 AACR (Free AACR Whitepaper) and ESMO (Free ESMO Whitepaper) conferences.

We also look forward to generating additive value in immunology with our novel ‘pro-resolutive monoclonal antibody’ platform with additional identified GPCR targets, as well as our ‘myeloid checkpoint’ and ‘cytokine’ drug discovery platforms of which the latest updates are steadily selected for presentation at international scientific congresses. In parallel, at early research level, we keep strengthening our first-in-kind platform built at the intersection of Antibody Engineering, Data Science, Artificial Intelligence (AI) and novel RNA Therapeutics technologies to develop next-generation immunotherapy medicines modulating immune cell responses in the field of immuno-inflammation and immuno-oncology.

Looking ahead to 2024, we are excited by several key clinical, preclinical and partnership milestones to advance the Company’s growth path with the involvement of our teams, experts and partners, all fully committed to innovation in service of patients".

Anne-Laure Autret-Cornet, Chief Financial Officer of OSE Immunotherapeutics, adds: "Our business-model is mostly based on recurrent and strategic partnerships with pharmaceutical companies. Thanks to the collaboration and license agreement signed with AbbVie, we strongly reinforced our financial visibility, which will allow us to pursue our investments in our proprietary clinical programs and our innovative R&D engine to increase their intrinsic value and to prepare the next wave of Company’s growth".

2023 FINANCIAL RESULTS

A meeting of the Board of Directors of OSE Immunotherapeutics was held on March 27, 2024. Following the Audit Committee opinion, the Board approved the annual and consolidated financial statements prepared under IFRS on 31 December 2023.

The key figures of the 2023 consolidated annual results are reported below (and presented in the attached tables):

In K€

December 31, 2023

December 31, 2022

Current operating result

(22,980)

(18,392)

Operating result

(22,986)

(18,476)

Net result

(23,221)

(17,760)

Available cash*

18,672

25,620

Consolidated balance sheet

82,054

91,781

As of December 31, 2023, the Company’s available cash totaled €18.7 million, versus €25.6 million as of December 31, 2022.

In 2024, the Company will reinforce its financial position with a $48 million upfront payment as part of the global and exclusive license and collaboration on OSE-230 signed with AbbVie in February 2024 giving a financial visibility until 2026.

In 2023, OSE Immunotherapeutics secured:

– An equity financing line with Vester Finance, set up on April 27, 2023. This financing has triggered at the end of September a capital increase of €11.6 million (without any discount on the share price at the date of signature). To supplement its financial resources and in order to extend its financial visibility until the fourth quarter of 2024, OSE Immunotherapeutics signed on 27 September 2023, an extension to this equity financing line agreement with Vester Finance, at the same conditions2.

This extension, approved by the Board of Directors of September 27, 2023, acting on delegation from the general assembly meeting of shareholders of June 22, 20233, relates to a maximum of 900,000 shares of the Company, representing a maximum of 4,16% of the share capital, that Vester committed to subscribe on its own initiative, over a maximum period of 24 months, subject to certain usual contractual conditions.

Assuming that the totality of this additional line of financing is used in full, a shareholder holding 1.00% of the capital of OSE Immunotherapeutics before its establishment, would see his stake increase to 0.96% of the capital on an undiluted basis4 and 0.96% of the share capital on a diluted basis5.

This transaction does not give rise to the preparation of a prospectus subject to the approval of the "Autorité des Marchés Financiers", based on Article 1 of the Prospectus Regulation granting an exemption when a transaction relates to a dilution less than 20% of the Company’s share capital.

The number of shares issued under this agreement and admitted to trading are communicated monthly on the Company’s website.

– Loans and "PGE Resilience"

The Company obtained the formal agreement on loans for a total amount of €5.3 million with the collective support of "La Région Pays de la Loire", Bpifrance and its banking pool composed by banks CIC, Crédit Mutuel and BNP to finance its strategic R&D programs. Favorable conditions were granted for these loans, with an interest range of 2-4% and reimbursement timelines within 3 to 5 years. Part of these loans is composed by a "PGE Resilience" ("Prêt Garanti par l’État") loan guaranteed by the French State, implemented in the context of the Ukrainian crisis.

2023 Financial results

The audit procedures on the consolidated accounts have been performed. The certification report will be issued after finalization of the procedures required for the purposes of filing the registration document.

The Company recorded a consolidated operating loss of €-23.0 million. Current operating expenses were €25.2 million (versus €36.6 million in 2022) of which 74% related to R&D. R&D expenses amounted to €17.1 million versus €26.9 million in 2022.

APPENDICES

CONSOLIDATED PROFIT & LOSS

P&L IN K€

December 31, 2023

December 31, 2022

Turnover

2,227

18,302

Total Revenues

2,227

18,302

Research and development expenses

(17,158)

(26,893)

Overhead expenses

(6,015)

(6,672)

Expenses related to shares payments

(2,034)

(3,130)

OPERATING PROFIT/LOSS – CURRENT

(22,980)

(18,392)

Other operating expenses

(6)

(84)

OPERATING PROFIT/LOSS

(22,986)

(18,476)

Financial products

2,177

2,079

Financial expenses

(2,412)

(1,624)

PROFIT/LOSS BEFORE TAX

(23,221)

(18,022)

Income Tax

219

263

NET PROFIT/LOSS

(23,003)

(17,760)

Of which consolidated net result attributable to shareholders

(23,003)

(17,760)

Net earnings attributable to shareholders

Weighted average number of shares outstanding

19,562,147

18,527,401

Basic earnings per share

(1.18)

(0.96)

Diluted earnings per share

(1.18)

(0.96)

IN K€

2023

2022

NET RESULT

(23,003)

(17,760)

Amounts to be recycled in the income statement:

Currency conversion difference

(77)

(61)

Amounts not to be recycled in the income statement:

(9)

122

Other comprehensive income in the period

(86)

(61)

GLOBAL PROFIT/LOSS

(23,089)

(17,699)

CONSOLIDATED BALANCE SHEET

ASSETS IN K€

December 31, 2023

December 31, 2022

Acquired R&D costs

46,401

48,784

Tangible assets

464

743

Right-of-use assets

3,606

4,236

Financial assets

910

635

Differed tax assets

195

182

TOTAL NON-CURRENT ASSETS

51 ,576

54,581

Trade receivables

982

403

Other current assets

10,824

11,177

Cash and cash equivalents

18,672

25,620

TOTAL CURRENT ASSETS

30,478

37,200

TOTAL ASSETS

82,054

91,781

EQUITY & LIABILITIES IN K€

December 31, 2023

December 31, 2022

SHAREHOLDERS’ EQUITY

Stated capital

4,330

3,705

Share premium

49,816

38,784

Merger premium

26,827

26,827

Treasury stock

(408)

(549)

Reserves and retained earnings

(34,587)

(18,349)

Consolidated result

(23,003)

(17,760)

TOTAL SHAREHOLDERS’ EQUITY

22,975

32,658

NON-CURRENT DEBTS

Non-current financial liabilities

35,508

37,231

Non-current lease liabilities

3,032

3,586

Non-current deferred tax liabilities

1,311

1,514

Non-current provisions

429

524

TOTAL NON-CURRENT DEBTS

40,280

42,856

CURRENT DEBTS

Current financial liabilities

6,403

3,093

Current lease liabilities

858

883

Trade payables

9,299

8,539

Corporate income tax liabilities

20

21

Social and tax payables

1,867

2,916

Other debts and accruals

351

816

TOTAL CURRENT DEBTS

18,799

16,268

TOTAL LIABILITIES

82,054

91,781

CONSOLIDATED CASH FLOW STATEMENTS

In K€

December 31, 2023

December 31, 2022

CONSOLIDATED RESULT

(23,003)

(17,760)

+/-

Depreciation, amortization and provision expenses

2,574

2,744

+

Amortization on "right-of-use"

846

742

+/-

Shares based payments (1)

1,746

2,728

CASH FLOW BEFORE TAX

(17,838)

(11,545)

+

Financial charges

(657)

(3,066)

–

Income tax expenses

(219)

(263)

–

Tax paid

(216)

(236)

+/-

Working capital variation (2)

(835)

(3,142)

CASH FLOW FROM OPERATING ACTIVITIES (A)

(19,764)

(18,252)

–

Tangible assets increase

(16)

(274)

+/-

Financial assets variation

0

0

+/-

Net variation in rights-of-use

(216)

0

+/-

Loans and advances variation

(275)

300

CASH FLOW FROM INVESTING ACTIVITIES (B)

(507)

26

+

Capital increase (including share premium)

11,357

+/-

Own shares transactions

0

+

Warrant subscription

300

+

Loan subscription

5,023

12,056

–

Loan repayment

(2,719)

(1,010)

–

Lease debt repayment (3)

(637)

(785)

–

Financial charges

CASH FLOW FROM FINANCING ACTIVITIES (C)

13,324

10,267

+/-

Currency translation transactions (D)

CASH VARIATION E = (A + B + C + D)

(6,948)

(7,959)

CASH OPENING BALANCE (F)

25,620

33,579

CASH CLOSING BALANCE (G)

18,672

25,620

DIFFERENCE: E (G-F)

0

(1) Warrants and free shares awards granted in 2023 and valuated for 1,746 K€
(2) Mainly explained by:
– Increase in trade receivable for 578 K€
Decrease in other current assets for 353 K€
– Increase in trade accounts payable for 759K€
– Decrease in social and tax payable for 1,048 K€
– Decrease in other debts for 464 K€
(3) Explained by IFRS16 application, which corresponds to reimbursement of lease debt for 637 K€

On March 27, 2024 Boundless Bio, Inc. (Nasdaq: BOLD), a clinical stage oncology company interrogating extrachromosomal DNA (ecDNA) biology to deliver transformative therapies to patients with previously intractable oncogene amplified cancers, reported the pricing of its initial public offering of 6,250,000 shares of its common stock at an initial public offering price of $16.00 per share (Press release, Boundless Bio, MAR 27, 2024, View Source [SID1234641519]). All of the shares are being offered by Boundless Bio. The gross proceeds from the offering, before deducting underwriting discounts and commissions and other offering expenses, are expected to be $100.0 million. Boundless Bio’s common stock is expected to begin trading on the Nasdaq Global Select Market on March 28, 2024 under the ticker symbol "BOLD." The offering is expected to close on April 2, 2024, subject to the satisfaction of customary closing conditions. In addition, Boundless Bio has granted the underwriters a 30-day option to purchase up to an additional 937,500 shares of common stock at the initial public offering price, less underwriting discounts and commissions.

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Goldman Sachs & Co. LLC, Leerink Partners, Piper Sandler and Guggenheim Securities are acting as joint book-running managers for the offering.

A registration statement relating to the offering has been filed with the Securities and Exchange Commission and was declared effective on March 27, 2024. The offering is being made only by means of a prospectus. When available, copies of the final prospectus may be obtained from Goldman Sachs & Co. LLC, Attention: Prospectus Department, 200 West Street, New York, NY 10282, by telephone at (866) 471-2526, or by email at [email protected]; Leerink Partners LLC, Attention: Syndicate Department, 53 State Street, 40th Floor, Boston, MA 02109, by telephone at (800) 808-7525, ext. 6105, or by email at [email protected]; Piper Sandler & Co., Attention: Prospectus Department, 800 Nicollet Mall, J12S03 Minneapolis, MN 55402, by telephone at (800) 747-3924, or by email at [email protected]; or Guggenheim Securities, LLC, Attention: Equity Syndicate Department, 330 Madison Avenue, 8th Floor, New York, NY 10017, by telephone at (212) 518-9544, or by email at [email protected].

This press release shall not constitute an offer to sell or a solicitation of an offer to buy these securities, nor shall there be any offer or sale of these securities in any state or jurisdiction in which such offer, solicitation, or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or jurisdiction.

On March 27, 2024 Aqtual, Inc., a precision medicine company using its novel cell-free DNA platform to develop products for chronic diseases and oncology, reported that it will present a poster at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, held April 5-10, 2024, in San Diego, California (Press release, Aqtual, MAR 27, 2024, View Source [SID1234641518]).

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"We have developed a plasma-based active chromatin capture method designed to capture both disease- and organ-specific molecular signals through a routine blood test," said Diana Abdueva, Ph.D., co-founder and CEO of Aqtual. "Our unique ability to analyze cell-free DNA derived from active chromatin enables comprehensive analysis of the epigenetic and transcriptomic landscape of both the tumor and immune components, providing novel insights that could help guide therapy selection and advance precision medicine."

Details of the poster presentation are as follows:

Poster Title: Detection of non-small cell lung and bladder cancer signatures in peripheral blood using a novel active chromatin capture assay
Date and Time: Tuesday, April 9, 9:00 AM – 12:30 PM
Session Category: Clinical Research
Session Title: Circulating Nucleic Acids 4
Location: Poster Section 40; Poster Board 15
Published Abstract Number: 5028

On March 27, 2024 CARsgen Therapeutics Holdings Limited (Stock Code: 2171.HK), a company focused on innovative CAR T-cell therapies for the treatment of hematologic malignancies and solid tumors, reported its 2023 Annual Results (Press release, Carsgen Therapeutics, MAR 27, 2024, View Source [SID1234641517]).

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Business Highlights

Zevorcabtagene autoleucel (CT053) NDA was approved by the NMPA.

Satricabtagene autoleucel (CT041) IND was approved by the NMPA for the postoperative adjuvant therapy of Claudin18.2 positive pancreatic cancer.

CT011 IND was approved by the NMPA for GPC3-positive stage IIIa hepatocellular carcinoma at high risk of recurrence after surgical resection.
Two hepatocellular carcinoma patients treated with a combination of local therapy and GPC3 CAR-T cells achieved disease-free survival exceeding 7 years.
CT071 IND was cleared by the FDA for relapsed/refractory multiple myeloma and relapsed/refractory primary plasma cell leukemia.
Developed a proprietary CARcelerateTM platform, shortening the manufacturing time to around 30 hours. The platform has been utilized for CT071.
CARsgen and Huadong Medicine entered into a collaboration agreement for the commercialization of zevorcabtagene autoleucel in mainland China.
CARsgen and Moderna initiated a collaboration agreement to investigate satricabtagene autoleucel in combination with an mRNA cancer vaccine.
Dr. Zonghai Li, Founder, Chairman of the Board, Chief Executive Officer, and Chief Scientific Officer of CARsgen Therapeutics, said, "In 2023, CARsgen remained dedicated to our vision, ‘Making Cancer Curable’ and were committed to reinforcing our team and improving operational efficiency. We made substantial progresses in the regulatory and clinical development of our innovative products and the advancement of new technology platforms. Multiple important milestones for different product candidates across clinical, regulatory, and business development were achieved. We are optimistic that we will navigate and overcome the challenges ahead with resilience and determination, advancing our innovative cell therapies."

Zevorcabtagene autoleucel (CT053) is an autologous fully human CAR T-cell product candidate against B-cell maturation antigen (BCMA) for the treatment of relapsed/refractory multiple myeloma (R/R MM). As informed by the NMPA on March 1, 2024, zevorcabtagene autoleucel was granted conditional approval on February 23, 2024 for the treatment of adult patients with relapsed or refractory multiple myeloma who have progressed after at least 3 prior lines of therapy (including a proteasome inhibitor and an immunomodulatory agent). An update from the Phase I study in China (NCT03975907) with 3-year follow-up was presented as a poster at the 2023 American Society of Hematology (ASH) (Free ASH Whitepaper) ("ASH") Annual Meeting in December 2023.

Satricabtagene autoleucel (CT041) is an autologous humanized CAR T-cell product candidate against Claudin18.2 (CLDN18.2), a membrane protein highly expressed in certain cancers. As of the date of the announcement, satricabtagene autoleucel, based on our information, is the world’s first CAR T-cell candidate for the treatment of solid tumors entering a Phase II clinical trial. In April 2023, satricabtagene autoleucel IND was approved by the National Medical Products Administration (NMPA) for the postoperative adjuvant therapy of Claudin18.2 positive pancreatic cancer (PC) (CT041-ST-05, NCT05911217). In May 2023, the Phase 2 part of the Phase 1b/2 clinical trial (NCT04404595) in the U.S. and Canada was initiated for the treatment of Claudin18.2 positive advanced gastric cancer/gastroesophageal junction cancer (GC/GEJ) in patients who have failed at least 2 prior lines of systemic therapies. Updates from the Phase 1b study in the U.S. (NCT04404595) were presented as a poster at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium ("ASCO GI").

CT011 is an autologous CAR T-cell product candidate against Glypican-3 (GPC3). In January 2024, CT011 IND was approved by the NMPA for GPC3-positive stage IIIa hepatocellular carcinoma at high risk of recurrence after surgical resection.

In July 2023, an article titled "Combined local therapy and CAR-GPC3 T-cell therapy in advanced hepatocellular carcinoma: a proof-of-concept treatment strategy" was published in Cancer Communication (London, England) demonstrating patients who received local therapy followed by sequential infusions of CAR-GPC3 T-cells achieved more than 7-year disease-free survival.

CT071 is an autologous fully human CAR T-cell therapy candidate against G protein-coupled receptor class C group 5 member D (GPRC5D) developed utilizing CARsgen’s proprietary CARcelerateTM platform for the treatment of R/R MM and relapsed/refractory primary plasma cell leukemia (R/R pPCL). The IND was cleared by the FDA on November 30, 2023 for R/R MM and R/R pPCL. An investigator-initiated trial (IIT) is ongoing in China to assess the safety and efficacy of CT071 in treating R/R MM and relapsed/refractory plasma cell leukemia (R/R PCL) (NCT05838131).

In January 2023, CARsgen and Huadong Medicine (Hangzhou) Co., Ltd., a wholly-owned subsidiary of Huadong Medicine Co., Ltd. (SZ. 000963) entered into a collaboration agreement for the commercialization of zevorcabtagene autoleucel, in mainland China.

In August 2023, CARsgen and Moderna, Inc. (Nasdaq: MRNA, "Moderna") have initiated a collaboration agreement to investigate satricabtagene autoleucel in combination with Moderna’s investigational Claudin18.2 mRNA cancer vaccine.

On March 27, 2024 Ascentage Pharma (6855.HK), a global biopharmaceutical company engaged in developing novel therapies for cancers, chronic hepatitis B (CHB), and age-related diseases, reported its annual results for the full year 2023 (Press release, Ascentage Pharma, MAR 27, 2024, View Source [SID1234641516]). During the reporting period, Ascentage Pharma made further strides in revenue generation through its commercialized product, achieved rapid progress with its patient-centric global innovation strategy, and delivered numerous milestones in clinical development and global expansion.

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Newly approved indication of olverembatinib expands the drug’s addressable market

In 2023, Ascentage Pharma recorded a revenue of RMB222 million, most of which was attributable to product sales and milestone payments, including a revenue of RMB194 million from product sales. For the first time, the company achieved commercial breakeven through topline growth while keeping selling and distribution expenses at a manageable level and significantly improving the efficiency of marketing activities.

Developed internally by Ascentage Pharma, olverembatinib is the first and only approved third-generation BCR-ABL inhibitor in China. In January 2023, as a Model Product of China-Developed Innovative Drugs, olverembatinib was included into the 2022 National Reimbursement Drug List (NRDL), a major step-forward that drastically improved the drug’s accessibility and paved the way for accelerated volume growth. Since its approval till December 31, 2023, olverembatinib generated an accumulated sales revenue of RMB362 million (audited, inclusive of value-added tax).

Meanwhile, Ascentage Pharma continued to strengthen its ability to drive revenue growth through product commercialization. On November 17, 2023, olverembatinib was approved for adult patients with chronic-phase chronic myeloid leukemia (CML-CP) resistant and/or intolerant of first-and second-generation tyrosine kinase inhibitors (TKIs). The indication expansion will allow a broader population of patients with CML to benefit from the drug and offer a new treatment option to drug-resistant patients, which will further olverembatinib’s commercial success. During the reporting period, the sales volume of olverembatinib increased 259%, the number of listed hospitals increased 567%, the total number of patients on treatment increased 123%. Looking ahead in 2024, with the approval of the new indication of olverembatinib, compounded by accelerated hospital listings, a growing number of patients on treatment, and ever longer duration of treatment, more patients will benefit from olverembatinib, driving the sales of the product.

Obtained clearances for five global registrational Phase III trials as the global innovation strategy began to bear fruit

Led by its global innovation strategy, Ascentage Pharma has delivered multiple milestones in clinical development as it effectively advanced global clinical development programs. Since the beginning of 2023, olverembatinib and the Bcl-2 inhibitor lisaftoclax (APG-2575) have been cleared to commence five global registrational Phase III studies, bolstering the company’s moat in the field of hematologic malignancies.

In February 2024, the US Food and Drug Administration (FDA) cleared a global registrational Phase III trial of olverembatinib in previously treated adult patients with CML-CP. This is the first global registrational Phase III trial of olverembatinib cleared by the US FDA and represents another step in Ascentage Phara’s growing presence in the global hematology arena. In January 2024, as a global best-in-class innovative drug from China, olverembatinib was included in the National Comprehensive Cancer Network (NCCN)’s latest guidelines for the management of CML. This inclusion highlights the therapeutic utility of olverembatinib and marks another major recognition from the global oncology community.

In addition to CML, olverembatinib has also made significant progress with its clinical development for the treatment of patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). In July 2023, the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) granted the clearance for the global registrational Phase III trial of olverembatinib in combination with chemotherapy versus imatinib in combination with chemotherapy for the treatment of newly diagnosed patients with Ph+ ALL, paving the way for olverembatinib to potentially become the first China-approved TKI for the treatment of patients with Ph+ ALL in the first-line setting.

Lisaftoclax obtained clearances for three global registrational Phase III studies. In August 2023, the US FDA cleared a global registrational Phase III study of lisaftoclax in previously treated patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). This regulatory clearance marked a major step-forward in the global clinical development of lisaftoclax as it can potentially accelerate the drug’s journey to market as the world’s second approved Bcl-2 inhibitor competing in the global market. Shortly after receiving this clearance, lisaftoclax was approved by the China CDE to enter a global registrational Phase III study of lisaftoclax combined with acalabrutinib, a Bruton’s tyrosine kinase (BTK) inhibitor, versus immunochemotherapy for the first-line treatment of patients with CLL/SLL. In December 2023, the China CDE approved another global registrational Phase III study of lisaftoclax for the first-line treatment of newly diagnosed elderly or unfit patients with acute myeloid leukemia (AML).

Promising clinical results underscore strong competitiveness in the field of hematologic malignancies

Pursuing its mission of addressing unmet clinical needs in China and around the world, Ascentage Pharma has built a rich pipeline composed of promising drug candidates with first-in-class and/or best-in-class potentials, and is conducting more than 40 clinical studies in China, the US, Australia, Europe, and Canada. The company’s innovative and clinical development capabilities have received growing recognition from the global research community as it continued to explore and validate the therapeutic potential of its drug candidates and frequently showcased new clinical data at major international congresses.

At the 65th American Society of Hematology (ASH) (Free ASH Whitepaper) (ASH 2023), Ascentage Pharma presented the latest results from multiple studies of olverembatinib and lisaftoclax, demonstrating the clinical advantages of these products.

Among those studies, two studies of olverembatinib were selected for Oral Presentations, making 2023 the sixth consecutive year in which data of olverembatinib were selected for Oral Presentations at the ASH (Free ASH Whitepaper) Annual Meeting. One of these Oral Presentations featured a registrational Phase II study evaluating the efficacy and safety of olverembatinib versus the best available therapy (BAT) in patients with CML-CP resistant and/or intolerant to prior treatment with TKIs. Results of the study showed that compared to the BAT, olverembatinib significantly improved the prognosis of patients with CML. The other Oral Presentation featured the preliminary results from a Phase II study of olverembatinib. Selected for "Highlights of ASH (Free ASH Whitepaper)", these results showed encouraging clinical benefit and favorable tolerability of an olverembatinib regimen that could potentially usher in an era of chemotherapy-free treatment for Ph+ ALL.

After releasing preliminary results from the US study of olverembatinib in an Oral Report at the ASH (Free ASH Whitepaper) Annual Meeting in 2022, at ASH (Free ASH Whitepaper) 2023, Ascentage Pharma presented updated data from a larger patient sample that showed the favorable clinical benefit and tolerability of olverembatinib, as a monotherapy and in combinations, in heavily pretreated patients with CML or Ph+ ALL, particularly those who have failed prior treatment with the third-generation TKI ponatinib or the allosteric STAMP inhibitor asciminib. These results suggest that olverembatinib has global best-in-class potential as an effective new therapy for patients with CML or Ph+ ALL.

Also at the 2023 ASH (Free ASH Whitepaper) Annual Meeting, Ascentage Pharma released results from three clinical studies of lisaftoclax, for the treatment of CLL, AML, and multiple myeloma (MM), separately. Among them, the study in patients with relapsed/refractory (R/R) CLL once again showed the favorable tolerability and significant efficacy of lisaftoclax. In particular, the company released the first dataset of lisaftoclax in MM and AML that reaffirmed the global best-in-class potential and unique therapeutic utility of lisaftoclax and provided strong evidence of the drug’s therapeutic applications to indications beyond CLL.

Prior to that, Ascentage Pharma presented updated clinical data of olverembatinib, lisaftoclax, the MDM2-p53 inhibitor alrizomadlin (APG-115), and the FAK/ALK/ROS1 inhibitor APG-2449, four of the company’s lead drug candidates, at the 59th American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (ASCO 2023). In particular, the data of olverembatinib showed promising clinical benefit and favorable tolerability in patients with TKI-resistant succinate dehydrogenase (SDH)-deficient gastrointestinal stromal tumor (GIST), thus indicating a potential breakthrough for an indication that currently has no effective treatment. Also in 2023, olverembatinib was granted a Breakthrough Therapy Designation (BTD) by the China CDE for the treatment of patients with SDH-deficient GIST who had received first-line treatment.

Building vertically integrated industrialization capabilities to further accelerate global expansion

Upholding its global innovation strategy, Ascentage Pharma is committed to building a large portfolio of global intellectual property rights. As of December 31, 2023, Ascentage Pharma holds 498 issued patents globally, among which 352 patents were issued overseas.

In addition, Ascentage Pharma received a zero-deficiency report from the Good Manufacturing Practice (GMP) compliance audit by a Qualified Person (QP) of the European Union (EU) in April 2023, which indicates that the company’s Global Manufacturing Center and its quality management system are now fully compliant with the GMP standards of the EU, generating extra tailwind to Ascentage Pharma’s ongoing transition towards a global biopharmaceutical company.

"In 2023, Ascentage Pharma has achieved multiple milestones across product commercialization, global clinical development, and corporate development, while continuing to showcase its prowess in global innovation," said Dr. Dajun Yang, Chairman and CEO of Ascentage Pharma. "The NRDL inclusion and newly approved indication of olverembatinib has further boosted the company’s commercialization capabilities. Meanwhile, olverembatinib, supported by its excellent efficacy and safety, was reaffirmed as a best-in-class drug and begun to show encouraging therapeutic value in additional indications that currently have no treatment options."

Dr. Yang continued, "In the past year, we accelerated our global clinical development programs and have in the process obtained clearances, including two from FDA, for five global registrational Phase III trials of olverembatinib and lisaftoclax. At the same time, our lead drug candidates continued to show clinical potential in additional indications, thus further strengthening our position in the field of hematologic malignancies."

In conclusion, Dr. Yang said, "Implementing our global innovation strategy with a patient-centric approach, we have built a rich pipeline that holds enormous clinical potential, particularly in hematologic malignancies. Moving forward, we will further enhance our commercialization and clinical development capabilities, and accelerate our global clinical development programs. Fulfilling the mission of addressing unmet clinical needs in China and around the world, we aim to bring our innovative drugs to the global market in the future for the benefit more patients around the world and create greater value for our communities and shareholders."