According to the terms of the agreement, BioNTech will acquire 100% of Pumis' issued share capital for a prepayment of $800 million (approximately RMB 5.781 billion) (subject to customary adjustment of the acquisition price), primarily in cash and a portion of American Depositary Shares (ADS). In addition, BioNTech will pay an additional milestone payment of up to $150 million (approximately RMB 1.084 billion) when Pumis meets the milestone conditions agreed upon by both parties. The transaction is expected to be completed in the first quarter of 2025, subject to customary delivery conditions and regulatory approvals.

After the completion of this transaction, BioNTech will acquire full rights to the Pumis candidate drug pipeline and its bispecific antibody drug development platform, further expanding its business scope in China; Pumis Zhuhai will serve as the BioNTech China R&D center to conduct related R&D research; The Pumis Nantong production base, which meets international standards, will contribute to BioNTech's future global product production and supply; Over 300 employees from Pumis' R&D, production, and support departments have joined BioNTech.

01. Excellent dual antibody performance in cooperation with Pumis
This merger is based on two previous collaborations between the two parties last year.

In July 2023, BioNTech reached a strategic research cooperation, project introduction selection, and global licensing agreement with Pumis Biotech. According to the terms of the agreement, BioNTech will obtain exclusive global selection rights for a preclinical bispecific antibody and a clinical monoclonal antibody used by Pumis for the treatment of malignant tumors. In addition, Pumis has granted exclusive authorization to BioNTech for multiple preclinical nanobody projects and provides designated targeted nanobody development services based on their needs.

Just four months later, both parties reached another cooperation agreement. BioNTech has obtained the development, production, and commercialization rights of Pumis anti-PD-L1/VEGF bispecific antibody (PM8002) globally (excluding Greater China) with a down payment of $55 million, development, registration, and commercial milestone payments of over $1 billion, and tiered sales commissions.

PM8002 is a bispecific antibody drug composed of a humanized anti-PD-L1 single domain antibody (VHH) fused onto an anti-VEGF-A IgG1 antibody containing an Fc silencing mutation. It has been extensively studied in multiple clinical trials targeting TNBC, small cell lung cancer, non-small cell lung cancer, cervical cancer, and other tumor types in China.

In December of that year, Pumis announced the efficacy of PM8002 combined with chemotherapy in the treatment of triple negative breast cancer (TNBC) at the 46th San Antonio breast cancer Seminar (SABCS). The results show that as of June 30, 2023, a total of 42 patients have received treatment and undergone at least one efficacy evaluation. The median duration of drug exposure was 4.6 months (range: 2.0 to 7.6 months). The optimal overall ORR was 78.6% (33/42), including 1 case of complete response (CR) and 32 cases of partial response (PR), of which 29 cases achieved response at the first assessment of the patient. The confirmed ORR is 71.4%, and the overall disease control rate (DCR) is 95.2%. The median time to remission (TTR) was 1.9 months (95% CI: 1.8-2.0). The optimal percentage change for the median target lesion is -47.2% (first quartile, third quartile: -56.9%, -33.5%). The median duration of remission (DOR) was 7.2 months, and the median progression free survival (PFS) was 9.2 months.

Since the beginning of this year, there have been frequent positive reports about the clinical progress of PM8002. In March, PM8002 was included in the breakthrough treatment category by the Drug Evaluation Center (CDE) of the State Food and Drug Administration, and its indication was the first-line treatment of inoperable local advanced/recurrent metastatic triple negative breast cancer with albumin binding paclitaxel for injection.

At the end of April, PM8002 was approved by the National Drug Administration (NMPA) to carry out a registered phase III clinical trial: a multicenter, randomized, double-blind phase III clinical study of PM8002 injection or placebo combined with albumin binding paclitaxel for injection for first-line treatment of inoperable locally advanced/recurrent metastatic triple negative breast cancer (TNBC). Later, we officially registered the Phase III clinical trial of PM8002 (20mg/kg Q2W) combined with chemotherapy for locally advanced or metastatic triple negative breast cancer on the website Clinicaltrials.gov.

A few days later, BioNTech announced the exercise of its first strategic partnership's global exclusive selection rights, obtaining the global development, production, and commercialization rights of preclinical bispecific antibody candidate drugs independently developed by Pumis.

According to the disclosure of the third quarter financial report of BioNTech in 2024, BNT327/PM8002 completed the first patient administration in the phase II clinical trial of breast cancer in October this year, aiming to evaluate the safety, efficacy and pharmacokinetics of this product in combination with chemotherapy at two dose levels and in the first-line and second-line treatment of locally advanced/metastatic triple negative breast cancer (TNBC) patients.

In terms of small cell lung cancer, BioNTech announced that it has completed the first patient administration of phase II clinical trials for small cell lung cancer in September, aiming to evaluate the efficacy of BNT327/PM8002 in combination with chemotherapy in untreated patients with extensive stage small cell lung cancer, as well as in patients with small cell lung cancer who have progressed after receiving first-line or second-line treatment. On the other hand, Pumis also launched a phase III clinical trial in September to evaluate the efficacy and safety of PM8002 combined with paclitaxel compared to second-line chemotherapy for small cell lung cancer.

02. 10 clinical research stage pipelines are currently being established to build an ADC technology platform
In addition to PM8002, Pumis is also advancing over 20 Class 1 biopharmaceutical projects, many of which are in the clinical research stage. The company has new drug research and development centers in Zhuhai, Suzhou, and Hong Kong, as well as clinical research centers in Shanghai and Beijing, and an industrial production base in Nantong. Pumis' core team has over 20 years of experience in high-end biopharmaceutical research and development, product application, and market launch.

From the perspective of technology platform, Pumis has established core technology platforms in antibody discovery, antibody engineering modification, discovery biology, preclinical, and CMC research, supporting the entire process of antibody new drug projects from antibody discovery to clinical application.

In terms of candidate pipelines, as of now, Pumis has 10 antibody new drug projects in the clinical research stage, and multiple clinical trials in phase II.

In addition to partnering with BioNTech, Pumis has also established strategic partnerships with multiple pharmaceutical companies. From an overseas perspective, at the beginning of this year, Pumis reached a strategic cooperation with Bitterroot Bio in the United States to jointly develop new bifunctional protein drugs that can be used to regulate the immune system and inflammatory response, thereby achieving the effect of treating various cardiovascular diseases.

Domestically, Pumis and Hanson Pharmaceuticals have once again expanded their strategic partnership since 2022, allowing Hanson Pharmaceuticals to use Pumis' independently developed anti EGFR/cMet bispecific antibody PM1080/HS-20117 for the development of antibody drug conjugates (ADCs) products. Pumis will receive a down payment from Hanson Pharmaceuticals and potential milestone payments for the development, registration, and commercialization of ADC products based on global net sales, totaling no more than RMB 5 billion, as well as a tiered royalty based on global net sales.

And this can also be roughly seen as Pumis' first step in exploring ADC. In this collaboration, Liu Xiaolin, co-founder, chairman, and CEO of Pumis, stated that the partnership will combine Pumis' advantages in dual antibody drug development with Hansen Pharmaceuticals' advantages in ADC development, and is expected to develop PM1080-ADC drugs with better clinical efficacy.

ADC is one of the popular varieties of domestically produced new drugs going global. Liu Xiaolin previously stated in an interview with 21st Century Business Herald that Pumis has already started building an ADC platform and believes that "with the arrival of the precision therapy era, ADC will replace chemotherapy. In the future, the combination therapy of 'IO (tumor immunotherapy)+ADC' has broad imagination space... The next stage of ADC drug development will return to the biological mechanism of related antibodies, including monoclonal antibodies, bispecific antibodies, etc. The functions of antibodies may play a more critical role, and antibody research and development is our strength. Pumis may play a more important role in this field.

03. BioNTech, which is irresistible to China's biotech industry
After partnering with Chinese Biotech seven times last year, BioNTech, which is deeply attached to Chinese Biotech, has not only launched new products but also made repeat purchases. Including achieving multi-target TMALIN with Yilian Biotech ® ADC Technology platform authorization agreement, further expanding global strategic partnerships, and reaching research cooperation and platform technology licensing agreements with 3D printing drug company San Di Ji. As of now, BioNTech has reached cooperation agreements with six Chinese biotech companies, with multiple transaction amounts exceeding 1 billion US dollars.

And the performance of Chinese biotech has also lived up to its mission. In addition to mentioning Pumis' PM8002, BioNTech's 2024 Q3 financial report also disclosed the progress of other key pipelines.

Firstly, there is a transaction with Yingen Biotechnology for three ADCs targeting HER2, B7H3, and TROP2.

Currently, BNT323/DB-1303 targeting HER2 is undergoing a phase 1/2 clinical trial (NCT05150691) evaluation in patients with advanced/unresectable, recurrent, or metastatic HER2 positive solid tumors. A group of advanced/recurrent endometrial cancer patients with HER2 expression positive (IHC3+, 2+, 1+or ISH positive) have completed enrollment. It is expected that data from this queue will be obtained in 2025.

In addition, a phase 3 clinical trial (NCT06340568) is being planned for patients with advanced endometrial cancer. It is estimated that in 2026, the preliminary data of the phase 3 clinical trials for patients with metastatic breast cancer with low expression of HR+and HER2 will be published, and these patients will progress after receiving hormone therapy and/or CDK4/6 inhibitor treatment.

BNT324/DB-1311 is an ADC drug targeting B7H3. In July of this year, the FDA awarded BNT324/DB-1311 orphan drug designation for the treatment of advanced or metastatic esophageal squamous cell carcinoma. A phase 1/2 clinical trial (NCT05914116) is currently underway for patients with advanced solid tumors. The first preliminary data update of the experiment is expected to be presented at the ESMO Asia Conference in December 2024.

Regarding the collaboration with Yilian Biosciences on BNT326/YL202, although a document submitted to the SEC in June this year revealed that due to multiple deaths observed by researchers in clinical trials, the FDA has decided to partially suspend the Phase 1 clinical trial of the product. However, at present, an international multicenter phase I clinical trial (NCT05653752) is under way, which evaluates BNT326/YL202 as a late stage treatment for patients with locally advanced or metastatic EGFR mutation non-small cell lung cancer or HR+/HER2 negative breast cancer. On August 15th of this year, the FDA lifted the partial clinical suspension of this trial. The trial recruitment has been restarted, with a focus on dose levels not exceeding 3 mg/kg, at which the safety situation is controllable and good clinical activity has been observed.

Source: https://pharm.jgvogel.cn/c1462180.shtml